2012
Marsalek B., Jancula D., Marsalkova E., Mashlan M., Safarova E., Tucek J., and Zboril R.:Multimodal Action and Selective Toxicity of Zerovalent Iron Nanoparticles against Cyanobacteria. Environ. Sci. Technol., 2012, 46 (4), pp 2316–2323 LINK
Abstract: Cyanobacteria pose a serious threat to water resources around the world. This is compounded by the fact that they are extremely resilient, having evolved numerous protective mechanisms to ensure their dominant position in their ecosystem. We show that treatment with nanoparticles of zerovalent iron (nZVI) is an effective and environmentally benign method for destroying and preventing the formation of cyanobacterial water blooms. The nanoparticles have multiple modes of action, including the removal of bioavailable phosphorus, the destruction of cyanobacterial cells, and the immobilization of microcystins, preventing their release into the water column. Ecotoxicological experiments showed that nZVI is a highly selective agent, having an EC50 of 50 mg/L against cyanobacteria; this is 20–100 times lower than its EC50 for algae, daphnids, water plants, and fishes. The primary product of nZVI treatment is nontoxic and highly aggregated Fe(OH)3, which promotes flocculation and gradual settling of the decomposed cyanobacterial biomass.
Hobza, P.: Calculations on Noncovalent Interactions and Databases of Benchmark Interaction Energies. Acc. Chem. Res., Articles ASAP (As Soon As Publishable) Publication Date (Web): January 6, 2012 (Article) LINK
Abstract: Although covalent interactions determine the primary structure of a molecule, the noncovalent interactions are responsible for the tertiary and quaternary structure of a molecule and create the fascinating world of the 3D architectures of biomacromolecules. For example, the double helical structure of DNA is of fundamental importance for the function of DNA: it allows it to store and transfer genetic information. To fulfill this role, the structure is rigid to maintain the double helix with a proper positioning of the complementary base, and floppy to allow for its opening. Very strong covalent interactions cannot fulfill both of these criteria, but noncovalent interactions, which are about 2 orders of magnitude weaker, can. This Account highlights the recent advances in the field of the design of novel wave function theory (WFT) methods applicable to noncovalent complexes ranging in size from less than 100 atoms, for which highly accurate ab initio methods are available, up to extended ones (several thousands atoms), which are the domain of semiempirical QM (SQM) methods.
Accurate interaction energies for noncovalent complexes are generated by the coupled-cluster technique, taking single- and double-electron excitations iteratively and triple-electron excitation perturbatively with a complete basis set description (CCSD(T)/CBS). The procedure provides interaction energies with high accuracy (error less than 1 kcal/mol). Because the method is computationally demanding, its application is limited to complexes smaller than 30 atoms. But researchers would also like to use computational methods to determine these interaction energies accurately for larger biological and nanoscale structures. Standard QM methods such as MP2, MP3, CCSD, or DFT fail to describe various types of noncovalent systems (H-bonded, stacked, dispersion-controlled, etc.) with comparable accuracy. Therefore, novel methods are needed that have been parametrized toward noncovalent interactions, and existing benchmark data sets represent an important tool for the development of new methods providing reliable characteristics of noncovalent clusters.
Our laboratory developed the first suitable data set of CCSD(T)/CBS interaction energies and geometries of various noncovalent complexes, called S22. Since its publication in 2006, it has frequently been applied in parametrization and/or verification of various wave function and density functional techniques. During the intense use of this data set, several inconsistencies emerged, such as the insufficient accuracy of the CCSD(T) correction term or its unbalanced character, which has triggered the introduction of a new, broader, and more accurate data set called the S66 data set. It contains not only 66 CCSD(T)/CBS interaction energies determined in the equilibrium geometries but also 1056 interaction energies calculated at the same level for nonequilibrium geometries. The S22 and S66 data sets have been used for the verification of various WFT methods, and the lowest RMSE (S66, in kcal/mol) was found for the recently introduced SCS-MI-CCSD/CBS (0.08), MP2.5/CBS (0.16), MP2.X/6-31G* (0.27), and SCS-MI-MP2/CBS (0.38) methods. Because of their computational economy, the MP2.5 and MP2.X/6-31G* methods can be recommended for highly accurate calculations of large complexes with up to 100 atoms.
The evaluation of SQM methods was based only on the S22 data set, and because some of these methods have been parametrized toward the same data set, the respective results should be taken with caution. For really extended complexes such as protein–ligand systems, only the SMQ methods are applicable. After adding the corrections to the dispersion energy and H-bonding, several methods exhibit surprisingly low RMSE (even below 0.5 kcal/mol). Among the various SMQ methods, the PM6-DH2 can be recommended because of its computational efficiency and it can be used for optimization (which is not the case for other SQM methods). The PM6-DH2 is the base of our novel scoring function used in in silico drug design.
Petr, J.; Maier, V.: Analysis of microorganisms by capillary electrophoresis. Trends in Analytical Chemistry, 2012, 31, 9 – 22.
Abstract: Microorganisms are well known for their positive, as well as negative, effects on health, which mean that there is a great need for methods of discovery, identification and determination of microorganisms. In the past decade, capillary electrophoresis (CE) began to be an interesting tool for analysis of microorganisms, interestingly sometimes with similar dimensions for the separation capillary and the microorganisms. This review focuses on the use of CE in the analysis of microorganisms. First, it looks at the origin of microbial surface charge and then describes key points in the analysis of microbes by capillary zone electrophoresis [first approaches using poly(ethylene oxide), covalent modification of the inner capillary wall, reversed electroosmotic flow, advances in detection, and on-line preconcentration] and capillary isoelectric focusing.
2011
Herchel, R.; Travnicek, Z. and Zboril, R.: Tuning of the Critical Temperature in Iron(II) Spin-Crossover Materials Based on Bridging Polycyanidometallates: Pentacyanidonitrosylferrate(II) and Hexacyanidoplatinate(IV), Inorg. Chem. 2011, 50 , 12390–12392. Link
Abstract: The reactions of iron(II) sulfate, 4-amino-3,5-di-2-pyridyl-4H-1,2,4-triazole (abpt), and pentacyanidonitrosylferrate(II) or hexacyanidoplatinate(IV) resulted in the formation of one-dimensional iron(II) spin-crossover compounds [Fe(abpt)(2)(μ-Fe(CN)(5)(NO))](n) (1) and [Fe(abpt)(2)(μ-Pt(CN)(6))](n) (2) with the spin-transition critical temperature near or above room temperature accompanied by thermochromism. Furthermore, it has been proven that the critical temperature T(c) is influenced by the type of dianionic polycyanidometallate within the series of discussed systems, and it changes in the sequence of [Fe(CN)(5)(NO)](2-) < [Pt(CN)(6))](2-) < [Ni(CN)(4))](2-) ≈ [Pd(CN)(4))](2-) ≈ [Pt(CN)(4))](2-).
Machala, L; Tuček, J and Zboril, R.: Polymorphous Transformations of Nanometric Iron(III) Oxide: A Review. Chem. Mater., Article ASAP Link
Cover designed by the authors of RCPTM
Abstract: There is great interest in iron oxides, especially in nanosized form, for both fundamental and practical reasons. Because of its polymorphism, iron(III) oxide (ferric oxide, Fe2O3) is one of the most interesting and potentially useful phases of the iron oxides. Each of the four different known crystalline Fe2O3 polymorphs (alpha-, beta-, gamma-, and epsilon-Fe2O3) has unique biochemical, magnetic, catalytic, and other properties that make it suitable for specific technical and biomedical applications. High temperature treatment is a key step in most syntheses of iron(III) oxides but often triggers polymorphous transformations that result in the formation of undesired mixtures of Fe2O3 polymorphs. It is therefore important to control the parameters that induce polymorphous transformations when seeking to prepare a given Fe2O3 polymorph as a single phase; identifying and understanding these parameters is a major challenge in the study of the polymorphism of solid compounds. This review discusses the dependence of the mechanism and kinetics of the polymorphous transformations of Fe2O3 on the intrinsic properties of the material (polymorph structure, particle size, particle morphology, surface coating, particle aggregation, incorporation of particles within a matrix) and external parameters of synthetic and/or natural conditions such as temperature, atmosphere, and pressure. The high-temperature and high-pressure induced transformations of Fe2O3 are reviewed in detail. In addition, the question of whether different Fe2O3 polymorphs are formed sequentially or simultaneously during thermal processes is discussed extensively, with reference to the experimental results that have been invoked to support these two different mechanisms. The use of selected analytical tools in studying the polymorphous transformations of Fe2O3 is also discussed, with particular emphasis on in situ approaches. Finally, key objectives for future research in this area are highlighted: (i) the development of more sophisticated kinetic control of the γ-Fe2O3 → ε-Fe2O3 phase transformation; (ii) investigation of particle morphology changes during the polymorphous transformations of Fe2O3; and (iii) the study of high-pressure induced phase transformations of Fe2O3 polymorphs other than α-Fe2O3.
Prucek, R.; Tucek, J.; Kilianova, M.; Panacek, A.; Kvitek, L.; Filip, J.; Kolar, M.; Tomankova, K. and Zboril R.: The targeted antibacterial and antifungal properties of magnetic nanocomposite of iron oxide and silver nanoparticles.
Biomaterials 2011, 32, 4704–4713. Link
Abstract: Two types of magnetic binary nanocomposites, Ag@Fe3O4 and γ-Fe2O3@Ag, were synthesized and characterized and their antibacterial activities were tested. As a magnetic component, Fe3O4 (magnetite) nanoparticles with an average size of about 70 nm and monodisperse γ-Fe2O3 (maghemite) nanoparticles with an average size of 5 nm were used. Nanocomposites were prepared via in situ chemical reduction of silver ions by maltose in the presence of particular magnetic phase and molecules of polyacrylate serving as a spacer among iron oxide and silver nanoparticles. In the case of the Ag@Fe3O4 nanocomposite, silver nanoparticles, caught at the surfaces of Fe3O4 nanocrystals, were around 5 nm in a size. On the contrary, in the case of the γ-Fe2O3@Ag nanocomposite, ultrafine γ-Fe2O3 nanoparticles surrounded silver nanoparticles ranging in a size between 20 and 40 nm. In addition, the molecules of polyacrylate in this nanocomposite type suppress considerably interparticle magnetic interactions as proved by magnetization measurements. Both synthesized nanocomposites exhibited very significant antibacterial and antifungal activities against ten tested bacterial strains (minimum inhibition concentrations (MIC) from 15.6 mg/L to 125 mg/L) and four candida species (MIC from 1.9 mg/L to 31.3 mg/L). Moreover, acute nanocomposite cytotoxicity against mice embryonal fibroblasts was observed at concentrations of higher than 430 mg/L (Ag@Fe3O4) and 292 mg/L (γ-Fe2O3@Ag). With respect to the non-cytotoxic nature of the polyacrylate linker, both kinds of silver nanocomposites are well applicable for a targeted magnetic delivery of silver nanoparticles in medicinal and disinfection applications.
Panáček, A.; Prucek, R.; Šafářová, D.; Dittrich, M.; Richtrová, J.; Beníčková, K.; Zbořil, R. and Kvítek, L.: Acute and Chronic Toxicity Effects of Silver Nanoparticles (NPs) on Drosophila melanogaster. Environ. Sci. Technol., Article ASAP, 2011. Link
Abstract: The use of nanoscaled materials is rapidly increasing, however, their possible ecotoxicological effects are still not precisely known. This work constitutes the first complex study focused on in vivo evaluation of the acute and chronic toxic effects and toxic limits of silver nanoparticles (NPs) on the eukaryotic organism Drosophila melanogaster. For the purpose of this study, silver NPs were prepared in the form of solid dispersion using microencapsulation method, where mannitol was used as an encapsulation agent. This newly prepared solid dispersion with a high concentration of silver NPs was exploited to prepare the standard Drosophila culture medium at a silver concentration range from 10 mg·L–1 to 100 mg·L–1 of Ag in the case of the acute toxicity testing and at a concentration equal to 5 mg·L–1 in the case of the chronic toxicity testing. The acute toxic effect of silver NPs onDrosophila melanogaster was observed for the silver concentration equal to 20 mg·L–1. At this silver concentration, 50% of the tested flies were unable to leave the pupae, and they did not finish their developmental cycle. Chronic toxicity of silver NPs was assessed by a long-term exposure of overall eight filial generations of Drosophila melanogaster to silver NPs. The long-term exposure to silver NPs influenced the fertility of Drosophila during the first three filial generations, nevertheless the fecundity of flies in subsequent generations consequently increased up to the level of the flies from the control sample due to the adaptability of flies to the silver NPs exposure.
Prucek, R.; Panáček, A.; Fargašová, A.; Ranc, V.; Mašek, V.; Kvítek, L. and Zbořil, R.: Re-crystallization of silver nanoparticles in a highly concentrated NaCl environment—a new substrate for surface enhanced IR-visible Raman spectroscopy. CrystEngComm, 2011, 13, 2242-2248. Link
Abstract: The common approach of silver nanoparticles activation for surface enhanced Raman spectroscopy often exploits an addition of chloride ions, generally at low concentrations of about 0.1–10 mM in the final dispersion. For the first time, we report the applicability of a highly concentrated NaCl solution (final concentration of 400 mM) for the SERS activation of silver nanoparticles ([similar]30 nm). Microscopic, optical and particle size distribution measurements reveal the rapid and reproducible re-crystallization of the primary silver nanoparticles to one-order larger crystallites ([similar]400 nm) already after 15 min after NaCl addition. The crystal growth mechanism is discussed with respect to the proved essential role of oxygen in the reaction system. The specific action of chloride ions is demonstrated through a comparison with NaBr and NaI solutions of the identical concentrations, which do not induce the analogous crystallization process. The recrystallized silver particles are efficient in an enhancement of the Raman signal not only for visible (488 nm) but also for near infrared laser excitation (1064 nm) as illustrated with the representative spectra of adenine.
Lemr, K.; Černoch, A.; Soubusta, J.; Kieling, K.; Eisert, J.; Dušek, M. Experimental Implementation of the Optimal Linear-Optical Controlled Phase Gate, Phys. Rev. Lett., 2011, 106, 013602. Link
Abstract: We report on the first experimental realization of optimal linear-optical controlled phase gates for arbitrary phases. The realized scheme is entirely flexible in that the phase shift can be tuned to any given value. All such controlled phase gates are optimal in the sense that they operate at the maximum possible success probabilities that are achievable within the framework of postselected linear-optical implementations with vacuum ancillas. The quantum gate is implemented by using bulk optical elements and polarization encoding of qubit states. We have experimentally explored the remarkable observation that the optimum success probability is not monotone in the phase.
2010
Ditzler, M.; Otyepka, M.; Sponer, J.; Walter, N. Molecular Dynamics and Quantum Mechanics of RNA: Conformational and Chemical Change We Can Believe In. Acc. Chem. Res., 2010, 1, 40-47. Link
Abstract: Structure and dynamics are both critical to RNA’s vital functions in biology. Numerous techniques can elucidate the structural dynamics of RNA, but computational approaches based on experimental data arguably hold the promise of providing the most detail. In this Account, we highlight areas wherein molecular dynamics (MD) and quantum mechanical (QM) techniques are applied to RNA, particularly in relation to complementary experimental studies. We have expanded on atomic-resolution crystal structures of RNAs in functionally relevant states by applying explicit solvent MD simulations to explore their dynamics and conformational changes on the submicrosecond time scale. MD relies on simplified atomistic, pairwise additive interaction potentials (force fields). Because of limited sampling, due to the finite accessible simulation time scale and the approximated force field, high-quality starting structures are required.
Tuček, J.; Zbořil, R.; Namai, A.; Ohkoshi, S. ε-Fe2O3: An Advanced Nanomaterial Exhibiting Giant Coercive Field, Millimeter-Wave Ferromagnetic Resonance, and Magnetoelectric Coupling, Chem. Mater. 2010, 22, 6483–6505. Link
Cover designed by the authors of RCPTM
Abstract: Nanosized iron oxides still attract significant attention within the scientific community, because of their application-promising properties. Among them, ε-Fe2O3 constitutes a remarkable phase, taking pride in a giant coercive field at room temperature, significant ferromagnetic resonance, and coupled magnetoelectric features that are not observed in any other simple metal oxide phase. In this work, we review basic structural and magnetic characteristics of this extraordinary nanomaterial with an emphasis on questionable and unresolved issues raised during its intense research in the past years. We show how a combination of various experimental techniques brings essential and valuable information, with regard to understanding the physicochemical properties of the ε-polymorph of Fe2O3, which remained unexplored for a long period of time. In addition, we recapitulate a series of synthetic routes that lead to the formation of ε-Fe2O3, highlighting their advantages and drawbacks. We also demonstrate how magnetic properties of ε-Fe2O3 can be tuned through the exploitation of various morphologies of ε-Fe2O3 nanosystems, the alignment of ε-Fe2O3 nanoobjects in a supporting matrix, and various degrees of cation substitution. Based on the current knowledge of the scientific community working in the field of ε-Fe2O3, we finally arrive at two main future challenges: (i) the search for optimal synthetic conditions to prepare single-phase ε-Fe2O3 with a high yield, desired size, morphology, and stability; and (ii) the search for a correct description of the magnetic behavior of ε-Fe2O3 at temperatures below the characteristic magnetic ordering temperature.
Trávníček, Z.; Štarha, P.; Popa I.; Vrzal, R.; Dvořák, Z. Roscovitine-Based CDK Inhibitors Acting as N-Donor Ligands in the Platinum(II) Oxalato Complexes: Preparation, Characterization and In Vitro Cytotoxicity, Eur. J. Med. Chem., 2010, 45, 4609-4614. Link
Abstract: The reactions of potassium bis(oxalato)platinate dihydrate with two molar equivalents of the potent adenine-based cyclin-dependent kinase inhibitor 2-(1-ethyl-2-hydroxyethylamino)-N6-(benzyl)-9-isopropyladenine (Roscovitine; Ros) and its benzyl-substituted analogues, i.e. 2-(1-ethyl-2-hydroxyethylamino)-N6-(2-methoxybenzyl)-9-isopropyladenine (2OMeRos), 2-(1-ethyl-2-hydroxyethylamino)-N6-(3-methoxybenzyl)-9-isopropyladenine (3OMeRos) and 2-(1-ethyl-2-hydroxyethylamino)-N6-(4-methoxybenzyl)-9-isopropyladenine (4OMeRos), were performed and the [Pt(ox)(Ros)(2)].(3/4)H(2)O (1), [Pt(ox)(2OMeRos)(2)].H(2)O (2), [Pt(ox)(3OMeRos)(2)].(1/2)H(2)O (3) and [Pt(ox)(4OMeRos)(2)].(3/4)H(2)O (4) platinum(II) oxalato complexes were obtained. The methods of the elemental analysis, IR, Raman and NMR spectroscopy, ESI + mass spectrometry, molar conductivity measurement and TG/DTA thermal analysis were performed to characterize the obtained products. The complexes 1-4 involve tetracoordinated central Pt(II) atom with one bidentate-coordinated oxalate dianion (ox) and two monodentate adenine-based molecules (nRos), thus giving the square-planar geometry around the metal centre with a PtN(2)O(2) donor set. In vitro cytotoxic activity of the complexes against ovarian carcinoma (A2780), cisplatin resistant ovarian carcinoma (A2780cis), malignant melanoma (G-361), lung carcinoma (A549), cervix epitheloid carcinoma (HeLa), breast adenocarcinoma (MCF7) and osteosarcoma (HOS) human cancer cell lines was evaluated. All the tested complexes exceeded the in vitro cytotoxicity of cisplatin and oxaliplatin against HeLa, A2780cis and, except for 2, also against HOS cancer cells. The complex 1 was also tested for its cytotoxicity in primary cultures of human hepatocytes and it was not found to be hepatotoxic up to the concentration of 50.0 microM.
Banas, P.; Walter, NG.; Sponer, J.; Otyepka, M. Protonation States of the Key Active Site Residues and Structural Dynamics of glmS Riboswitch as Revealed by Molecular Dynamics, J. Phys. Chem. B, 2010, 26, 8701-8712. Link
Cover designed by the authors of RCPTM
Abstract: The glmS catalytic riboswitch is part of the 5′-untranslated region of mRNAs encoding glucosamine-6-phosphate (GlcN6P) synthetase (glmS) in numerous Gram-positive bacteria. Binding of the cofactor GlcN6P induces site-specific self-cleavage of the RNA. However, the detailed reaction mechanism as well as the protonation state of the glmS reactive form still remains elusive. To probe the dominant protonation states of key active site residues, we carried out explicit solvent molecular dynamic simulations involving various protonation states of three crucial active site moieties observed in the available crystal structures: (i) guanine G40 (following the Thermoanaerobacter tengcongensis numbering), (ii) the GlcN6P amino/ammonium group, and (iii) the GlcN6P phosphate moiety. We found that a deprotonated G40− seems incompatible with the observed glmS active site architecture. Our data suggest that the canonical form of G40 plays a structural role by stabilizing an in-line attack conformation of the cleavage site A-1(2′-OH) nucleophile, rather than a more direct chemical role. In addition, we observe weakened cofactor binding upon protonation of the GlcN6P phosphate moiety, which explains the experimentally observed increase in Km with decreasing pH. Finally, we discuss a possible role of cofactor binding and its interaction with the G65 and G1 purines in structural stabilization of the A-1(2′-OH) in-line attack conformation. On the basis of the identified dominant protonation state of the reaction precursor, we propose a hypothesis of the self-cleavage mechanism in which A-1(2′-OH) is activated as a nucleophile by the G1(pro-Rp) nonbridging oxygen of the scissile phosphate, whereas the ammonium group of GlcN6P acts as the general acid protonating the G1(O5′) leaving group.
Riley, K. E.; Pitoňák, M.; Jurečka, P.; Hobza, P. Stabilization and Structure Calculations for Noncovalent Interactions in Extended Molecular Systems Based on Wave Function and Density Functional Theories, Chem. Rev. 2010, 110, 5023–5063. Link
Abstract: In the recent years, substantial improvements have been achieved in the field of non-empirical accurate quantum chemical calculations, such as density functional based symmetry adapted perturbation theory and diffusion quantum Monte Carlo calculations. Agreement of their results with the reference coupled cluster treatment at the complete basis set limit has established a consensus about the quality of the reference data and put accuracy assessment on firm ground. Availability of accurate reference data contributed a great deal to development of fast and reliable quantum mechanical methodologies. In the current review we encompass recent developments in the field of accurate reference quantum mechanical calculations, facilitate orientation among the quickly appearing treatments, and emphasize the vital importance of accurate reference calculations for development of model chemistries.
Zbořil, R.; Karlický, F.; Bourlinos, A. B.; Steriotis, T. A.; Stubos, A. K.; Georgakilas, V.; Šafářová, K.; Jančík, D.; Trapalis, C.; Otyepka, M. Graphene Fluoride: A Stable Stoichiometric Graphene Derivative and Its Chemical Conversion to Graphene, Small 2010, 6, 2885-2891. Link
Abstract: Stoichoimetric graphene fluoride monolayers are obtained in a single step by the liquid-phase exfoliation of graphite fluoride with sulfolane. Comparative quantum-mechanical calculations reveal that graphene fluoride is the most thermodynamically stable of five studied hypothetical graphene derivatives; graphane, graphene fluoride, bromide, chloride, and iodide. The graphene fluoride is transformed into graphene via graphene iodide, a spontaneously decomposing intermediate. The calculated bandgaps of graphene halides vary from zero for graphene bromide to 3.1 eV for graphene fluoride. It is possible to design the electronic properties of such two-dimensional crystals.
Dallas, P.; Tucek, J.; Jancik, D.; Kolar, M.; Panacek, A.; Zboril, R. Magnetically Controllable Silver Nanocomposite with Multifunctional Phosphotriazine Matrix and High Antimicrobial Activity, Adv. Funct. Mater. 2010, 20, 2347-2354. Link
Abstract: A recently developed multi-functional phosphotriazine-based polymer is used as a matrix for embedding γ-Fe2O3 nanoparticles as well as a suitable chemical template for surface modification with silver nanoparticles. For the primary magnetic modification, maghemite nanoparticles are surface modified with oleic acid in order to render them organophilic and to prevent the aggregation of the nanoparticles. This aggregation could occur as the polymer synthesis, based on reaction of phosphonitrilic chlorine and 1,4-phenylenediamine, takes place in toluene. The surface active amine units of the polymer structure enable the reduction of silver cations to silver nanoparticles, which are well attached and finely dispersed on its surface. The developed nanocomposite represents one of the few magnetically controllable antibacterial agents based on silver nanoparticles. Magnetic measurements reveal the completely suppressed interactions among maghemite nanoparticles because of their perfect surface coating with an organic surfactant and fine dispersion inside the polymer matrix. This magnetic nanocomposite exhibits a high antibacterial and antifungal activity as proven by tests with nine bacterial strains and four candida (yeast genus) species. For the majority of the tested species, the minimum-inhibition concentrations are below 100 mg L-1, which is comparable to their equivalent minimum-inhibition concentrations in colloidal silver systems.
Sivula, K.; Zboril, R.; Le Formal, F.; Robert, R.; Weidenkaff, A.; Tucek, J.; Frydrych, J.; Gratzel, M. Photoelectrochemical Water Splitting with Mesoporous Hematite Prepared by a Solution-Based Colloidal Approach, J. Am. Chem. Soc. 2010, 132, 7436-7444. Link
Abstract: Sustainable hydrogen production through photoelectrochemical water splitting using hematite (α-Fe2O3) is a promising approach for the chemical storage of solar energy, but is complicated by the material’s nonoptimal optoelectronic properties. Nanostructuring approaches have been shown to increase the performance of hematite, but the ideal nanostructure giving high efficiencies for all absorbed light wavelengths remains elusive. Here, we report for the first time mesoporous hematite photoelectodes prepared by a solution-based colloidal method which yield water-splitting photocurrents of 0.56 mA cm−2under standard conditions (AM 1.5G 100 mW cm−2, 1.23 V vs reversible hydrogen electrode, RHE) and over 1.0 mA cm−2 before the dark current onset (1.55 V vs RHE). The sintering temperature is found to increase the average particle size, and have a drastic effect on the photoactivity. X-ray photoelectron spectroscopy and magnetic measurements using a SQUID magnetometer link this effect to the diffusion and incorporation of dopant atoms from the transparent conducting substrate. In addition, examining the optical properties of the films reveals a considerable change in the absorption coefficient and onset properties, critical aspects for hematite as a solar energy converter, as a function of the sintering temperature. A detailed investigation into hematite’s crystal structure using powder X-ray diffraction with Rietveld refinement to account for these effects correlates an increase in a C3v-type crystal lattice distortion to the improved optical properties.
Nachtigallova, D.; Zeleny, T.; Ruckenbauer, M.; Muller, H.; Barbatti, M.; Hobza, P.; Lischka, H. Does Stacking Restrain the Photodynamics of Individual Nucleobases? J. Am. Chem. Soc. 2010, 132, 8261-8263. Link
Abstract: Nonadiabatic photodynamical simulations of 4-aminopyrimidine (4-APy) used as a model for adenine were performed by embedding it between two stacking methyl-guanine (mGua) molecules to determine the effect of spatial restrictions on the ultrafast photodeactivation mechanism of this nucleobase. A hybrid multiconfigurational ab initio/molecular mechanical approach in combination with surface hopping was used. During the dynamics the formation of a significant fraction of intrastrand hydrogen bonding from 4-APy to mGua above and below is observed. These findings show that this type of hydrogen bond may play an important role for the photodynamics within one DNA strand and that it should be of interest even in irregular segments of double stranded nucleic acids structures. The relaxation mechanism of internal conversion to the ground state is dominated by ring puckering, and an overall elongation of the lifetime of the embedded system by 20% as compared to the isolated 4-APy is computed.
2009
Herchel, R.; Šindelář, Z.; Trávníček, Z.; Zbořil, R.; Vančo, J. Novel 1D Chain Fe(III)-salen-like Complexes Involving Anionic Heterocyclic N-Donor Ligands. Synthesis, X-ray Structure, Magnetic, 57Fe Mössbauer, and Biological Activity Studies, Dalton Trans. 2009, 9870-9880. Link
Abstract: The iron(III) salen-type complexes [Fe(salen)(L)]n (1–6) involving heterocyclic N-donor ligands HL {HL = 1H-imidazole (Himz), 1H-tetrazol-5-amine (Hatz), 5-methyl-1H-tetrazole (Hmtz), 1H-benzimidazole (Hbimz), 1H-1,2,4-triazole (Htriz) and 1H-benzotriazole (Hbtriz)} have been prepared and characterised by elemental analysis, FT IR, CI mass and 57Fe Mössbauer spectroscopies, and variable temperature magnetic measurements. Single crystal X-ray analysis of [Fe(salen)(btriz)]n (6) revealed a 1D chain-polymeric structure of the complex with the btriz anion as a bridging ligand. Magnetic data for all complexes were fitted using Fisher’s model (for S = 5/2) and also using a heptanuclear closed ring model showing a weak antiferromagnetic interaction (J≈−1 to −2 cm−1), and moreover, molecule-based magnet properties have been observed in the case of [Fe(salen)(atz)]n (2). The exponential correlation between the magnetic properties (the isotropic exchange parameter J) and the basicity of the free ligands (Kb) has been found. The antiferromagnetic ordering as well as a moderate structural dissimilarity in the vicinity of iron atoms has been proved by the 57Fe Mössbauer low-temperature (2 K) in-field (7 T) experiments in the case of (2), in which two sextets with the line intensities (3/4/1/3/4/1) have been observed. The compounds have been tested for their SOD-like activity, DNA cleavage activity, and in vitro cytotoxicity against two human cancer cell lines: chronic myelogenous erythroleukemia (K562) and breast adenocarcinoma (MCF7). The best result regarding the cytotoxicity has been achieved for the complex of [Fe(salen)(atz)]n (2), where IC50 = 6.4 μM against K562.
Pól, J.; Vidová, V.; Kruppa,G.; Kobliha, V.; Novák, P.; Lemr, K.; Kotiaho, T.; Kostiainen, R.; Havlíček, V.; Volný, M. Automated Ambient Desorption−Ionization Platform for Surface Imaging Integrated with a Commercial Fourier Transform Ion Cyclotron Resonance Mass Spectrometer Anal. Chem. 2009, 20, 8479–8487. Link
Abstract:A fully automated atmospheric pressure ionization platform has been built and coupled with a commercial high-resolution Fourier transform ion cyclotron resonance mass spectrometer (FTICR-MS) instrument. The outstanding performance of this instrument allowed screening on the basis of exact masses in imaging mode. The main novel aspect was in the integration of the atmospheric pressure ionization imaging into the current software for matrix-assisted laser desorption ionization (MALDI) imaging, which allows the user of this commercial dual-source mass spectrometer to perform MALDI-MS and different ambient MS imaging from the same user interface and to utilize the same software tools. Desorption electrospray ionization (DESI) and desorption atmospheric pressure photoionization (DAPPI) were chosen to test the ambient surface imaging capabilities of this new ionization platform. Results of DESI imaging experiments performed on brain tissue sections are in agreement with previous MS imaging reports obtained by DESI imaging, but due to the high resolution and mass accuracy of the FTICR instrument it was possible to resolve several ions at the same nominal mass in the DESI-MS spectra of brain tissue. These isobaric interferences at low resolution are due to the overlap of ions from different lipid classes with different biological relevance. It was demonstrated that with the use of high-resolution MS fast imaging screening of lipids can be achieved without any preseparation steps. DAPPI, which is a relatively new and less developed ambient ionization technique compared to DESI, was used in imaging mode for the first time ever. It showed promise in imaging of phytocompounds from plant leaves, and selective ionization of a sterol lipid was achieved by DAPPI from a brain tissue sample.
Bourlinos, A. B.; Georgakilas, V.; Zboril, R.; Steriotis, T. A.; Stubos, A. K. Liquid-Phase Exfoliation of Graphite Towards Solubilized Graphenes, Small 2009, 5, 1841-1845. Link
Abstract:In summary, we have introduced a new series of solvents to extract solubilized graphenes from graphite powder. The first set comprises certain electron-deficient perfluorinated aromatic compounds, whereas the second set refers to the aromatic heterocycle of pyridine. Along with these liquids, some other dispersing media have been also listed. Depending on the solvent, graphite can be dispersed at variable concentrations and yields resulting in clear, stable colloids containing solubilized graphenes. We also demonstrated that the as-produced single layers can be easily converted into gold–graphene hybrids through wet chemistry. The solubility of graphite in such a wide range of solvents is believed to facilitate a broad spectrum of organic reactions with miscible reagents as well as solution processing of several polymer composites.
Kluchova, K.; Zboril, R.; Tucek, J.; Pecova, M.; Zajoncova, L.; Safarik, I.; Mashlan, M.; Markova, I.; Jancik, D.; Sebela, M.; Bartonkova, H.; Bellesi, V.; Novak, P.; Petridis, D. Superparamagnetic Maghemite Nanoparticles from Solid-State Synthesis – Their Functionalization Towards Peroral MRI Contrast Agent and Magnetic Carrier for Trypsin Immobilization, Biomaterials 2009, 30, 2855-2863. Link
Abstract: Nearly monodispersed superparamagnetic maghemite nanoparticles (15–20 nm) were prepared by a one-step thermal decomposition of iron(II) acetate in air at 400 °C. The presented synthetic route is simple, cost effective and allows to prepare the high-quality superparamagnetic particles in a large scale. The as-prepared particles were exploited for the development of magnetic nanocomposites with the possible applicability in medicine and biochemistry. For the purposes of the MRI diagnostics, the maghemite particles were simply dispersed in the bentonite matrix. The resulting nanocomposite represents very effective and cheap oral negative contrast agent for MRI of the gastrointestinal tract and reveals excellent contrast properties, fully comparable with those obtained for commercial contrast material. The results of the clinical research of this maghemite–bentonite contrast agent for imaging of the small bowel are discussed. For biochemical applications, the primary functionalization of the prepared maghemite nanoparticles with chitosan was performed. In this way, a highly efficient magnetic carrier for protein immobilization was obtained as demonstrated by conjugating thermostable raffinose-modified trypsin (RMT) using glutaraldehyde. The covalent conjugation resulted in a further increase in trypsin thermostability (T50 = 61 °C) and elimination of its autolysis. Consequently, the immobilization of RMT allowed fast in-solution digestion of proteins and their identification by MALDI–TOF mass spectrometry.
Pavlova, M.; Klvana, M.; Prokop, Z.; Chaloupkova, R.; Banas, P.; Otyepka, M.; Wade, R. C.; Tsuda, M.; Nagata, Y.; Damborsky, J. Redesigning Dehalogenase Access Tunnels as a Strategy for Degrading an Anthropogenic Substrate, Nature Chem. Biol.2009, 5, 727-733. Link
Abstract: Engineering enzymes to degrade anthropogenic compounds efficiently is challenging. We obtained Rhodococcus rhodochrous haloalkane dehalogenase mutants with up to 32-fold higher activity than wild type toward the toxic, recalcitrant anthropogenic compound 1,2,3-trichloropropane (TCP) using a new strategy. We identified key residues in access tunnels connecting the buried active site with bulk solvent by rational design and randomized them by directed evolution. The most active mutant has large aromatic residues at two out of three randomized positions and two positions modified by site-directed mutagenesis. These changes apparently enhance activity with TCP by decreasing accessibility of the active site for water molecules, thereby promoting activated complex formation. Kinetic analyses confirmed that the mutations improved carbon-halogen bond cleavage and shifted the rate-limiting step to the release of products. Engineering access tunnels by combining computer-assisted protein design with directed evolution may be a valuable strategy for refining catalytic properties of enzymes with buried active sites.
Panacek, A.; Kolar, M.; Vecerova, R.; Prucek, R.; Soukupova, J.; Krystof, V.; Hamal, P.; Zboril, R.; Kvitek, L. Antifungal Activity of Silver Nanoparticles Against Candida spp, Biomaterials 2009, 30, 6333-6340. Link
Abstract: The antifungal activity of the silver nanoparticles (NPs) prepared by the modified Tollens process was evaluated for pathogenic Candida spp. by means of the determination of the minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC), and the time-dependency of yeasts growth inhibition. Simultaneously the cytotoxicity of the silver NPs to human fibroblasts was determined. The silver NPs exhibited inhibitory effect against the tested yeasts at the concentration as low as 0.21 mg/L of Ag. The inhibitory effect of silver NPs was enhanced through their stabilization and the lowest MIC equal to 0.05 mg/L was determined for silver NPs stabilized by sodium dodecyl sulfate against Candida albicans II. The obtained MICs of the silver NPs and especially of the stabilized silver NPs were comparable and in some cases even better than MICs of the conventional antifungal agents determined by E-test. The silver NPs effectively inhibited the growth of the tested yeasts at the concentrations below their cytotoxic limit against the tested human fibroblasts determined at a concentration equal to 30 mg/L of Ag. In contrast, ionic silver inhibited the growth of the tested yeasts at the concentrations comparable to the cytotoxic level (approx. 1 mg/L) of ionic silver against the tested human fibroblasts.
Peřina, Jr., J.; Lukš, A.; Haderka, O.; Scalora, M. Surface Spontaneous Parametric Down-Conversion, Phys. Rev. Lett. 2009, 103, 063902-1-063902-4. Link
Abstract: Surface spontaneous parametric down-conversion is predicted as a consequence of continuity requirements for electric- and magnetic-field amplitudes at a discontinuity of χ(2) nonlinearity. A generalization of the usual two-photon spectral amplitude is suggested to describe this effect. Examples of nonlinear layered structures and periodically poled nonlinear crystals show that surface contributions to spontaneous down-conversion can be important.
2008
Cerny, J.; Kabelac, M.; Hobza, P.; Double-Helical -> Ladder Structural Transition in the B-DNA is Induced by a Loss of Dispersion Energy, J. Am. Chem. Soc. 2008, 130, 16055-16059. Link
Abstract: The role of the dispersion energy and electrostatic energy on the geometry and stability of theB-DNA helix was investigated. Both molecular dynamics simulations with empirical force field and hybridquantum mechanical/molecular mechanics molecular dynamics simulations, where the dispersion orelectrostatics term is suppressed/increased, on the one hand and an ab initio minimization procedure onthe other have shown that the lack of the dispersion term leads to an increase of the vertical separation ofthe bases as well as to a loss of helicity, thus resulting in a ladder-like structure. A decrease of theelectrostatic term produces a separation of the DNA strands. The biological consequences of bothelectrostatic and dispersion forces in DNA are enormous, and without either of them, DNA would becomeunstable and unable to provide the storage and transfer of genetic information.
Vančo, J.; Marek, J.; Trávníček, Z.; Račanská, E.; Muselík, J.; Švajlenová, O. Synthesis, Structural Characterization, Antiradical and Antidiabetic Activities of Copper(II) and Zinc(II) Schiff Base Complexes Derived from Salicylaldehyde and β-Alanine, J. Inorg. Biochem. 2008, 102, 595-605. Link
Abstract: A series of copper(II) and zinc(II) complexes involving a tridentate O,N,O’-donor Schiff base derived from salicylaldehyde and β-alanine {i.e. N-salicylidene-β-alanine(2-), (L)}, having the composition [Cu2(L)2(H2O)]·H2O (1), [Cu(L)(H2O)]n (2), and [Zn(L)(H2O)]n (3), have been prepared and characterized by elemental analyses, UV–visible (UV–VIS), FT-IR and ESI-MS spectra, and thermal analyses. Complexes 1 and 2 have been investigated by single crystal X-ray analysis and also by temperature dependent magnetic susceptibility measurements (294–80 K). All prepared complexes have been evaluated by the antiperoxynitrite activity assay and alloxan-induced diabetes model. The significant antioxidant and antidiabetic activities have been found in the case of both copper(II) complexes 1 and 2. In spite of first two complexes, the zinc(II) complex 3, as well as the potassium salt of the ligand (KHL) showed only insignificant protective effect against the tyrosine nitration in vitro.
Trávníček, Z.; Mikulík, J.; Čajan, M.; Zbořil, R.; Popa, I. Novel iron complexes bearing N6-substituted adenosine derivatives: Synthesis, magnetic, 57Fe Mössbauer, DFT, and in vitro cytotoxicity studies, Bioorg. Med. Chem. 2008, 16, 8719-8728.Link
Abstract: Iron complexes (1–7) involving N6-benzyladenosine derivatives of the predominant composition [Fe(Ln)Cl3] · H2O {where L1 = N6-(2-fluorobenzyl)adenosine (1), L2 = N6-(4-fluorobenzyl)adenosine (2), L3 = N6-(2-trifluoromethylbenzyl)adenosine (3), L4 = N6-(3-trifluoromethylbenzyl)adenosine (4), L5 = N6-(4-trifluoromethylbenzyl)adenosine (5), L6 = N6-(4-trifluoromethoxybenzyl)adenosine (6), and L7 = N6-(4-chlorobenzyl)adenosine (7)} have been synthesized. The compounds have been characterized by elemental analysis, variable-temperature and in-field 57Fe Mössbauer, ES+ MS, FTIR, 1H and 13C NMR spectroscopies, magnetochemical and conductivity measurements, thermal (TGA/DSC/DTA) analyses, and DFT calculations. It has been found that the organic molecule is coordinated to iron via N7 atom of the appropriate adenosine derivative and the products are represented by mixtures of complexes with various iron oxidation (FeIII/FeII) and spin states (S = 5/2, 4/2, 3/2, 2/2) and geometries (tetrahedral or trigonal bipyramidal). It is caused by the fact that partial redox processes proceed during the reactions due to the presence of a ribose moiety, which is oxidized to the corresponding 5′-ribotic acid, and simultaneously, a portion of FeIII cations is reduced to FeII ones. Moreover, a significant effect of crystal water molecules on stereochemistry, and hence, on magnetic and spectral properties of the prepared complexes has been found. The compounds have been tested for their in vitro cytotoxicity against the following human cancer cell lines: malignant melanoma (G-361), osteogenic sarcoma (HOS), chronic myelogenous leukemia (K-562), and breast adenocarcinoma (MCF-7). The most important results have been obtained for complex 2 with IC50 values 8–16 μM against HOS, K-562, and MCF-7 cell lines, and for complex 6 with IC50 value 4 μM against MCF-7 cell line.
Dvořák, Z.; Vrzal, R.; Henklová, P.; Jančová, P.; Anzenbacherová, E.; Maurel, P.; Švecová, L.; Pavek, P.; Ehrmann, J.; Havlík, R.; Bednář, P.; Lemr, K.; Ulrichová, J. JNK Inhibitor SP600125 is a Partial Agonist of Human Aryl Hydrocarbon Receptor and Induces CYP1A1 and CYP1A2 Genes in Primary Human Hepatocytes, Biochem. Pharmacol. 2008, 75, 580-588. Link
Abstract: SP600125, a specific inhibitor of c-Jun-N-Terminal kinase (JNK), was reported as a ligand and antagonist of aryl hydrocarbon receptor (AhR) [Joiakim A, Mathieu PA, Palermo C, Gasiewicz TA, Reiners Jr JJ. The Jun N terminal kinase inhibitor SP600125 is a ligand and antagonist of the aryl hydrocarbon receptor. Drug Metab Dispos 2003;31(11):1279–82]. Here we show that SP600125 is not an antagonist but a partial agonist of human AhR. SP600125 significantly induced CYP1A1 and CYP1A2 mRNAs in primary human hepatocytes and CYP1A1 mRNA in human hepatoma cells HepG2. This effect was abolished by resveratrol, an antagonist of AhR. Consistent with the recent report, SP600125 dose-dependently inhibited CYP1A1 and CYP1A2 genes induction by a prototype AhR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in human hepatocytes. Moreover, SP600125 displayed typical behavior of a partial agonist in HepG2 cells transiently transfected with a reporter plasmid containing two inverted repeats of the dioxin responsive element or with a plasmid containing 5′-flanking region of human CYP1A1 gene. SP600125 transactivated the reporter plasmids with EC50 of 0.005 and 1.89 μM, respectively. On the other hand, TCDD-dependent transactivation of the reporter plasmids was inhibited by SP600125 with IC50 values of 1.54 and 2.63 μM, respectively. We also tested, whether the effects of SP600125 are due to metabolism. Using liquid chromatography/mass spectrometry approach, we observed formation of two minor monohydroxylated metabolites of SP600125 in human hepatocytes, human liver microsomes but not in HepG2 cells. These data imply that biotransformation is not responsible for the effects of SP600125 on AhR signaling. In conclusion, we demonstrate that SP600125 is a partial agonist of human AhR, which induces CYP1A genes.
2007
The Pierre Auger Collaboration, Correlation of the Highest-Energy Cosmic Rays with Nearby Extragalactic Objects, Science 2007, 318, 938-943. Link
Abstract: Using data collected at the Pierre Auger Observatory during the past 3.7 years, we demonstrated a correlation between the arrival directions of cosmic rays with energy above 6 × 1019 electron volts and the positions of active galactic nuclei (AGN) lying within 75 megaparsecs. We rejected the hypothesis of an isotropic distribution of these cosmic rays with at least a 99% confidence level from a prescribed a priori test. The correlation we observed is compatible with the hypothesis that the highest-energy particles originate from nearby extragalactic sources whose flux has not been substantially reduced by interaction with the cosmic background radiation. AGN or objects having a similar spatial distribution are possible sources.
Hermanek, M.; Zboril, R.; Medrik, I.; Pechousek, J.; Gregor, C. Catalytic Efficiency of Iron(III) Oxides in Decomposition of Hydrogen Peroxide: Competition between the Surface Area and Crystallinity of Nanoparticles, J. Am. Chem. Soc. 2007, 129, 10929-10936. Link
Abstract: Various iron(III) oxide catalysts were prepared by controlled decomposition of a narrow layer (ca. 1 mm) of iron(II) oxalate dihydrate, FeC2O4·2H2O, in air at the minimum conversion temperature of 175 °C. This thermally induced solid-state process allows for simple synthesis of amorphous Fe2O3 nanoparticles and their controlled one-step crystallization to hematite (α-Fe2O3). Thus, nanopowders differing in surface area and particle crystallinity can be produced depending on the reaction time. The phase composition of iron(III) oxides was monitored by XRD and 57Fe Mössbauer spectroscopy including in-field measurements, providing information on the relative contents of amorphous and crystalline phases. The gradual changes in particle size and surface area accompanying crystallization were evaluated by HRTEM and BET analysis, respectively. The catalytic efficiency of the synthesized nanoparticles was tested by tracking the decomposition of hydrogen peroxide. The obtained kinetic data gave an unconventional nonmonotone dependence of the rate constant on the surface area of the samples. The amorphous nanopowder with the largest surface area of 401 m2 g-1 revealed the lowest catalytic efficiency, while the highest efficiency was achieved with the sample having a significantly lower surface area, 337 m2 g-1, exhibiting a prevailing content of crystalline α-Fe2O3 phase. The obtained rate constant, 26.4 × 10-3 min-1 (g/L)-1, is currently the highest value published. The observed rare catalytic phenomenon, where the particle crystallinity prevails over the surface area effects, is discussed with respect to other processes of heterogeneous catalysis.
Cvek, B.; Dvořák, Z. Targeting of Nuclear Factor-κB and Proteasome by Dithiocarbamate Complexes with Metals, Curr. Pharm. Des. 2007, 13, 3155-3167. Link
Abstract: Dithiocarbamates and their complexes with transition metals have been used as common pesticides, vulcanizing or analytical agents for decades. These compounds are one of the most reported inhibitors of nuclear factor-κB (NF-κB) signaling cascade. Recently, it has been found that dithiocarbamates are very potent inhibitors of proteasome. NF-κB plays a central role in the immune system and is described as a major actor in many of human cancers mainly because of its protective effects against apoptosis. Molecular mechanisms involved in regulation and function of NF-κB pathway have been elucidated recently. In particular, pivotal zinc containing proteins that alter NF-κB signal transduction were recognized. Additionally, proteasome system was found to be a key player in NF-κB pathway and is an attractive target for anticancer drug development. Collectively, the capability of dithiocarbamates to inhibit NF-κB and proteasome makes these compounds promising anticancer agents. This review focuses on the biological activity of dithiocarbamate coordination compounds with regard to their possible molecular targets in NF-κB signaling and proteasome (JAMM domain proteins). Future research should aim to find the most suitable dithiocarbamate coordination compounds for treatment of cancer and other diseases.
2006
Panacek, A.; Kvitek, L.; Prucek, R.; Kolar, M.; Vecerova, R.; Pizurova, N.; Sharma, V. K.; Nevecna, T.; Zboril, R. Silver Colloid Nanoparticles: Synthesis, Characterization, and Their Antibacterial Activity, J. Phys. Chem. B 2006, 110, 16248-16253. Link
Abstract: A one-step simple synthesis of silver colloid nanoparticles with controllable sizes is presented. In this synthesis, reduction of [Ag(NH3)2]+ complex cation by four saccharides was performed. Four saccharides were used: two monosaccharides (glucose and galactose) and two disaccharides (maltose and lactose). The syntheses performed at various ammonia concentrations (0.005−0.20 mol L-1) and pH conditions (11.5−13.0) produced a wide range of particle sizes (25−450 nm) with narrow size distributions, especially at the lowest ammonia concentrations. The average size, size distribution, morphology, and structure of particles were determined by dynamic light scattering (DLS), transmission electron microscopy (TEM), and UV/Visible absorption spectrophotometry. The influence of the saccharide structure (monosacharides versus disaccharides) on the size of silver particles is briefly discussed. The reduction of [Ag(NH3)2]+ by maltose produced silver particles with a narrow size distribution with an average size of 25 nm, which showed high antimicrobial and bactericidal activity against Gram-positive and Gram-negative bacteria, including highly multiresistant strains such as methicillin-resistant Staphylococcus aureus. Antibacterial activity of silver nanoparticles was found to be dependent on the size of silver particles. A very low concentration of silver (as low as 1.69 μg/mL Ag) gave antibacterial performance.
Petrek, M.; Otyepka, M.; Banas, P.; Kosinova, P.; Koca, J.; Damborsky, J. CAVER: A new tool to explore routes from protein clefts, pockets and cavities, BMC Bioinformatics, 2006, 7 , 316. Link
Abstract: The main aim of this study was to develop and implement an algorithm for the rapid, accurate and automated identification of paths leading from buried protein clefts, pockets and cavities in dynamic and static protein structures to the outside solvent. Results: The algorithm to perform a skeleton search was based on a reciprocal distance function grid that was developed and implemented for the CAVER program. The program identifies and visualizes routes from the interior of the protein to the bulk solvent. CAVER was primarily developed for proteins, but the algorithm is sufficiently robust to allow the analysis of any molecular system, including nucleic acids or inorganic material. Calculations can be performed using discrete structures from crystallographic analysis and NMR experiments as well as with trajectories from molecular dynamics simulations. The fully functional program is available as a stand-alone version and as plug-in for the molecular modeling program PyMol. Additionally, selected functions are accessible in an online version. Conclusion: The algorithm developed automatically finds the path from a starting point located within the interior of a protein. The algorithm is sufficiently rapid and robust to enable routine analysis of molecular dynamics trajectories containing thousands of snapshots. The algorithm is based on reciprocal metrics and provides an easy method to find a centerline, i.e. the spine, of complicated objects such as a protein tunnel. It can also be applied to many other molecules. CAVER is freely available from the web site Caver.Despite a large success of CAVER software, it has been outperformed by MOLE, which is more robust and quicker.
Trávníček, Z.; Kryštof, V.; Šipl, M. Zinc(II) complexes with potent cyclin-dependent kinase inhibitors derived from 6-benzylaminopurine: Synthesis, characterization, X-ray structures and biological activity. J. Inorg. Biochem., 2006, 2, 214-225. Link
Abstract: The synthesis, characterization and biological activity of the first zinc(II) complexes with potent inhibitors of cyclin-dependent kinases (CDKs) derived from 6-benzylaminopurine are described. Based on the results following from elemental analyses, infrared, NMR and ES+MS (electrospray mass spectra in the positive ion mode) spectroscopies, conductivity data, thermal analysis and X-ray structures, the tetrahedral Zn(II) complexes of the compositions [Zn(Olo)Cl(2)](n) (1), [Zn(iprOlo)Cl(2)](n) (2), [Zn(BohH(+))Cl(3)] x H(2)O (3) and [Zn(iprOloH(+))Cl(3)] x H(2)O (4) have been prepared, where Olo=2-(2-hydroxyethylamino)-6-benzylamino-9-methylpurine (Olomoucine), iprOlo=2-(2-hydroxyethylamino)-6-benzylamino-9-isopropylpurine (i-propyl-Olomoucine), Boh=2-(3-hydroxypropylamino)-6-benzylamino-9-isopropylpurine (Bohemine). The 1D-polymeric chain structure for [Zn(Olo)Cl(2)](n) (1) as well as the monomeric one for [Zn(BohH(+))Cl(3)] x H(2)O (3) and [Zn(iprOloH(+))Cl(3)] x H(2)O (4) have been revealed unambiguously by single crystal X-ray analyses. The 1D-polymeric chain of 1 consists of Zn(Olo)Cl(2) monomeric units in which the Zn(II) ion is coordinated by two chlorine atoms and one oxygen atom of the 2-hydroxyethylamino group of Olomoucine. The next monomeric unit is bonded to Zn(II) through the N7 atom of a purine ring. Thus, each of Zn(II) ions is tetrahedrally coordinated and a ZnCl(2)NO chromophore occurs in the complex 1. The complexes 3 and 4 are mononuclear species with a distorted tetrahedral arrangement of donor atoms around the Zn(II) ion with a ZnCl(3)N chromophore. The corresponding CDK inhibitor, i.e., both Boh and iprOlo, is coordinated to Zn(II) via the N7 atom of the purine ring in 3 and 4. The cytotoxicity of the zinc(II) complexes against human melanoma, sarcoma, leukaemia and carcinoma cell lines has been determined as well as the inhibition of the CDK2/cyclin E kinase. A relationship between the structure and biological activity of the complexes is also discussed.
2011
Herchel, R.; Travnicek, Z. and Zboril, R. Tuning of the Critical Temperature in Iron(II) Spin-Crossover Materials Based on Bridging Polycyanidometallates: Pentacyanidonitrosylferrate(II) and Hexacyanidoplatinate(IV), Inorg. Chem. 2011, 50 , 12390–12392. Link
Abstract: The reactions of iron(II) sulfate, 4-amino-3,5-di-2-pyridyl-4H-1,2,4-triazole (abpt), and pentacyanidonitrosylferrate(II) or hexacyanidoplatinate(IV) resulted in the formation of one-dimensional iron(II) spin-crossover compounds [Fe(abpt)(2)(μ-Fe(CN)(5)(NO))](n) (1) and [Fe(abpt)(2)(μ-Pt(CN)(6))](n) (2) with the spin-transition critical temperature near or above room temperature accompanied by thermochromism. Furthermore, it has been proven that the critical temperature T(c) is influenced by the type of dianionic polycyanidometallate within the series of discussed systems, and it changes in the sequence of [Fe(CN)(5)(NO)](2-) < [Pt(CN)(6))](2-) < [Ni(CN)(4))](2-) ≈ [Pd(CN)(4))](2-) ≈ [Pt(CN)(4))](2-).
Cover designed by the authors of RCPTM
Abstract: There is great interest in iron oxides, especially in nanosized form, for both fundamental and practical reasons. Because of its polymorphism, iron(III) oxide (ferric oxide, Fe2O3) is one of the most interesting and potentially useful phases of the iron oxides. Each of the four different known crystalline Fe2O3 polymorphs (alpha-, beta-, gamma-, and epsilon-Fe2O3) has unique biochemical, magnetic, catalytic, and other properties that make it suitable for specific technical and biomedical applications. High temperature treatment is a key step in most syntheses of iron(III) oxides but often triggers polymorphous transformations that result in the formation of undesired mixtures of Fe2O3 polymorphs. It is therefore important to control the parameters that induce polymorphous transformations when seeking to prepare a given Fe2O3 polymorph as a single phase; identifying and understanding these parameters is a major challenge in the study of the polymorphism of solid compounds. This review discusses the dependence of the mechanism and kinetics of the polymorphous transformations of Fe2O3 on the intrinsic properties of the material (polymorph structure, particle size, particle morphology, surface coating, particle aggregation, incorporation of particles within a matrix) and external parameters of synthetic and/or natural conditions such as temperature, atmosphere, and pressure. The high-temperature and high-pressure induced transformations of Fe2O3 are reviewed in detail. In addition, the question of whether different Fe2O3 polymorphs are formed sequentially or simultaneously during thermal processes is discussed extensively, with reference to the experimental results that have been invoked to support these two different mechanisms. The use of selected analytical tools in studying the polymorphous transformations of Fe2O3 is also discussed, with particular emphasis on in situ approaches. Finally, key objectives for future research in this area are highlighted: (i) the development of more sophisticated kinetic control of the γ-Fe2O3 → ε-Fe2O3 phase transformation; (ii) investigation of particle morphology changes during the polymorphous transformations of Fe2O3; and (iii) the study of high-pressure induced phase transformations of Fe2O3 polymorphs other than α-Fe2O3.
Prucek, R.; Tucek, J.; Kilianova, M.; Panacek, A.; Kvitek, L.; Filip, J.; Kolar, M.; Tomankova, K. and Zboril R., The targeted antibacterial and antifungal properties of magnetic nanocomposite of iron oxide and silver nanoparticles, Biomaterials 2011, 32, 4704–4713. Link
Abstract: Two types of magnetic binary nanocomposites, Ag@Fe3O4 and γ-Fe2O3@Ag, were synthesized and characterized and their antibacterial activities were tested. As a magnetic component, Fe3O4 (magnetite) nanoparticles with an average size of about 70 nm and monodisperse γ-Fe2O3 (maghemite) nanoparticles with an average size of 5 nm were used. Nanocomposites were prepared via in situ chemical reduction of silver ions by maltose in the presence of particular magnetic phase and molecules of polyacrylate serving as a spacer among iron oxide and silver nanoparticles. In the case of the Ag@Fe3O4 nanocomposite, silver nanoparticles, caught at the surfaces of Fe3O4 nanocrystals, were around 5 nm in a size. On the contrary, in the case of the γ-Fe2O3@Ag nanocomposite, ultrafine γ-Fe2O3 nanoparticles surrounded silver nanoparticles ranging in a size between 20 and 40 nm. In addition, the molecules of polyacrylate in this nanocomposite type suppress considerably interparticle magnetic interactions as proved by magnetization measurements. Both synthesized nanocomposites exhibited very significant antibacterial and antifungal activities against ten tested bacterial strains (minimum inhibition concentrations (MIC) from 15.6 mg/L to 125 mg/L) and four candida species (MIC from 1.9 mg/L to 31.3 mg/L). Moreover, acute nanocomposite cytotoxicity against mice embryonal fibroblasts was observed at concentrations of higher than 430 mg/L (Ag@Fe3O4) and 292 mg/L (γ-Fe2O3@Ag). With respect to the non-cytotoxic nature of the polyacrylate linker, both kinds of silver nanocomposites are well applicable for a targeted magnetic delivery of silver nanoparticles in medicinal and disinfection applications.
Panáček, A.; Prucek, R.; Šafářová, D.; Dittrich, M.; Richtrová, J.; Beníčková, K.; Zbořil, R. and Kvítek, L. Acute and Chronic Toxicity Effects of Silver Nanoparticles (NPs) on Drosophila melanogaster, Environ. Sci. Technol., Article ASAP, 2011. Link
Abstract: The use of nanoscaled materials is rapidly increasing, however, their possible ecotoxicological effects are still not precisely known. This work constitutes the first complex study focused on in vivo evaluation of the acute and chronic toxic effects and toxic limits of silver nanoparticles (NPs) on the eukaryotic organism Drosophila melanogaster. For the purpose of this study, silver NPs were prepared in the form of solid dispersion using microencapsulation method, where mannitol was used as an encapsulation agent. This newly prepared solid dispersion with a high concentration of silver NPs was exploited to prepare the standard Drosophila culture medium at a silver concentration range from 10 mg·L–1 to 100 mg·L–1 of Ag in the case of the acute toxicity testing and at a concentration equal to 5 mg·L–1 in the case of the chronic toxicity testing. The acute toxic effect of silver NPs onDrosophila melanogaster was observed for the silver concentration equal to 20 mg·L–1. At this silver concentration, 50% of the tested flies were unable to leave the pupae, and they did not finish their developmental cycle. Chronic toxicity of silver NPs was assessed by a long-term exposure of overall eight filial generations of Drosophila melanogaster to silver NPs. The long-term exposure to silver NPs influenced the fertility of Drosophila during the first three filial generations, nevertheless the fecundity of flies in subsequent generations consequently increased up to the level of the flies from the control sample due to the adaptability of flies to the silver NPs exposure.
Prucek, R.; Panáček, A.; Fargašová, A.; Ranc, V.; Mašek, V.; Kvítek, L. and Zbořil, R. Re-crystallization of silver nanoparticles in a highly concentrated NaCl environment—a new substrate for surface enhanced IR-visible Raman spectroscopy, CrystEngComm, 2011, 13, 2242-2248. Link
Abstract: The common approach of silver nanoparticles activation for surface enhanced Raman spectroscopy often exploits an addition of chloride ions, generally at low concentrations of about 0.1–10 mM in the final dispersion. For the first time, we report the applicability of a highly concentrated NaCl solution (final concentration of 400 mM) for the SERS activation of silver nanoparticles ([similar]30 nm). Microscopic, optical and particle size distribution measurements reveal the rapid and reproducible re-crystallization of the primary silver nanoparticles to one-order larger crystallites ([similar]400 nm) already after 15 min after NaCl addition. The crystal growth mechanism is discussed with respect to the proved essential role of oxygen in the reaction system. The specific action of chloride ions is demonstrated through a comparison with NaBr and NaI solutions of the identical concentrations, which do not induce the analogous crystallization process. The recrystallized silver particles are efficient in an enhancement of the Raman signal not only for visible (488 nm) but also for near infrared laser excitation (1064 nm) as illustrated with the representative spectra of adenine.
Lemr, K.; Černoch, A.; Soubusta, J.; Kieling, K.; Eisert, J.; Dušek, M. Experimental Implementation of the Optimal Linear-Optical Controlled Phase Gate, Phys. Rev. Lett., 2011, 106, 013602. Link
Abstract: We report on the first experimental realization of optimal linear-optical controlled phase gates for arbitrary phases. The realized scheme is entirely flexible in that the phase shift can be tuned to any given value. All such controlled phase gates are optimal in the sense that they operate at the maximum possible success probabilities that are achievable within the framework of postselected linear-optical implementations with vacuum ancillas. The quantum gate is implemented by using bulk optical elements and polarization encoding of qubit states. We have experimentally explored the remarkable observation that the optimum success probability is not monotone in the phase.
2010
Ditzler, M.; Otyepka, M.; Sponer, J.; Walter, N. Molecular Dynamics and Quantum Mechanics of RNA: Conformational and Chemical Change We Can Believe In. Acc. Chem. Res., 2010, 1, 40-47. Link
Abstract: Structure and dynamics are both critical to RNA’s vital functions in biology. Numerous techniques can elucidate the structural dynamics of RNA, but computational approaches based on experimental data arguably hold the promise of providing the most detail. In this Account, we highlight areas wherein molecular dynamics (MD) and quantum mechanical (QM) techniques are applied to RNA, particularly in relation to complementary experimental studies. We have expanded on atomic-resolution crystal structures of RNAs in functionally relevant states by applying explicit solvent MD simulations to explore their dynamics and conformational changes on the submicrosecond time scale. MD relies on simplified atomistic, pairwise additive interaction potentials (force fields). Because of limited sampling, due to the finite accessible simulation time scale and the approximated force field, high-quality starting structures are required.
Tuček, J.; Zbořil, R.; Namai, A.; Ohkoshi, S. ε-Fe2O3: An Advanced Nanomaterial Exhibiting Giant Coercive Field, Millimeter-Wave Ferromagnetic Resonance, and Magnetoelectric Coupling, Chem. Mater. 2010, 22, 6483–6505. Link
Cover designed by the authors of RCPTM
Abstract: Nanosized iron oxides still attract significant attention within the scientific community, because of their application-promising properties. Among them, ε-Fe2O3 constitutes a remarkable phase, taking pride in a giant coercive field at room temperature, significant ferromagnetic resonance, and coupled magnetoelectric features that are not observed in any other simple metal oxide phase. In this work, we review basic structural and magnetic characteristics of this extraordinary nanomaterial with an emphasis on questionable and unresolved issues raised during its intense research in the past years. We show how a combination of various experimental techniques brings essential and valuable information, with regard to understanding the physicochemical properties of the ε-polymorph of Fe2O3, which remained unexplored for a long period of time. In addition, we recapitulate a series of synthetic routes that lead to the formation of ε-Fe2O3, highlighting their advantages and drawbacks. We also demonstrate how magnetic properties of ε-Fe2O3 can be tuned through the exploitation of various morphologies of ε-Fe2O3 nanosystems, the alignment of ε-Fe2O3 nanoobjects in a supporting matrix, and various degrees of cation substitution. Based on the current knowledge of the scientific community working in the field of ε-Fe2O3, we finally arrive at two main future challenges: (i) the search for optimal synthetic conditions to prepare single-phase ε-Fe2O3 with a high yield, desired size, morphology, and stability; and (ii) the search for a correct description of the magnetic behavior of ε-Fe2O3 at temperatures below the characteristic magnetic ordering temperature.
Trávníček, Z.; Štarha, P.; Popa I.; Vrzal, R.; Dvořák, Z. Roscovitine-Based CDK Inhibitors Acting as N-Donor Ligands in the Platinum(II) Oxalato Complexes: Preparation, Characterization and In Vitro Cytotoxicity, Eur. J. Med. Chem., 2010, 45, 4609-4614. Link
Abstract: The reactions of potassium bis(oxalato)platinate dihydrate with two molar equivalents of the potent adenine-based cyclin-dependent kinase inhibitor 2-(1-ethyl-2-hydroxyethylamino)-N6-(benzyl)-9-isopropyladenine (Roscovitine; Ros) and its benzyl-substituted analogues, i.e. 2-(1-ethyl-2-hydroxyethylamino)-N6-(2-methoxybenzyl)-9-isopropyladenine (2OMeRos), 2-(1-ethyl-2-hydroxyethylamino)-N6-(3-methoxybenzyl)-9-isopropyladenine (3OMeRos) and 2-(1-ethyl-2-hydroxyethylamino)-N6-(4-methoxybenzyl)-9-isopropyladenine (4OMeRos), were performed and the [Pt(ox)(Ros)(2)].(3/4)H(2)O (1), [Pt(ox)(2OMeRos)(2)].H(2)O (2), [Pt(ox)(3OMeRos)(2)].(1/2)H(2)O (3) and [Pt(ox)(4OMeRos)(2)].(3/4)H(2)O (4) platinum(II) oxalato complexes were obtained. The methods of the elemental analysis, IR, Raman and NMR spectroscopy, ESI + mass spectrometry, molar conductivity measurement and TG/DTA thermal analysis were performed to characterize the obtained products. The complexes 1-4 involve tetracoordinated central Pt(II) atom with one bidentate-coordinated oxalate dianion (ox) and two monodentate adenine-based molecules (nRos), thus giving the square-planar geometry around the metal centre with a PtN(2)O(2) donor set. In vitro cytotoxic activity of the complexes against ovarian carcinoma (A2780), cisplatin resistant ovarian carcinoma (A2780cis), malignant melanoma (G-361), lung carcinoma (A549), cervix epitheloid carcinoma (HeLa), breast adenocarcinoma (MCF7) and osteosarcoma (HOS) human cancer cell lines was evaluated. All the tested complexes exceeded the in vitro cytotoxicity of cisplatin and oxaliplatin against HeLa, A2780cis and, except for 2, also against HOS cancer cells. The complex 1 was also tested for its cytotoxicity in primary cultures of human hepatocytes and it was not found to be hepatotoxic up to the concentration of 50.0 microM.
Banas, P.; Walter, NG.; Sponer, J.; Otyepka, M. Protonation States of the Key Active Site Residues and Structural Dynamics of glmS Riboswitch as Revealed by Molecular Dynamics, J. Phys. Chem. B, 2010, 26, 8701-8712. Link
Cover designed by the authors of RCPTM
Abstract: The glmS catalytic riboswitch is part of the 5′-untranslated region of mRNAs encoding glucosamine-6-phosphate (GlcN6P) synthetase (glmS) in numerous Gram-positive bacteria. Binding of the cofactor GlcN6P induces site-specific self-cleavage of the RNA. However, the detailed reaction mechanism as well as the protonation state of the glmS reactive form still remains elusive. To probe the dominant protonation states of key active site residues, we carried out explicit solvent molecular dynamic simulations involving various protonation states of three crucial active site moieties observed in the available crystal structures: (i) guanine G40 (following the Thermoanaerobacter tengcongensis numbering), (ii) the GlcN6P amino/ammonium group, and (iii) the GlcN6P phosphate moiety. We found that a deprotonated G40− seems incompatible with the observed glmS active site architecture. Our data suggest that the canonical form of G40 plays a structural role by stabilizing an in-line attack conformation of the cleavage site A-1(2′-OH) nucleophile, rather than a more direct chemical role. In addition, we observe weakened cofactor binding upon protonation of the GlcN6P phosphate moiety, which explains the experimentally observed increase in Km with decreasing pH. Finally, we discuss a possible role of cofactor binding and its interaction with the G65 and G1 purines in structural stabilization of the A-1(2′-OH) in-line attack conformation. On the basis of the identified dominant protonation state of the reaction precursor, we propose a hypothesis of the self-cleavage mechanism in which A-1(2′-OH) is activated as a nucleophile by the G1(pro-Rp) nonbridging oxygen of the scissile phosphate, whereas the ammonium group of GlcN6P acts as the general acid protonating the G1(O5′) leaving group.
Riley, K. E.; Pitoňák, M.; Jurečka, P.; Hobza, P. Stabilization and Structure Calculations for Noncovalent Interactions in Extended Molecular Systems Based on Wave Function and Density Functional Theories, Chem. Rev. 2010, 110, 5023–5063. Link
Abstract: In the recent years, substantial improvements have been achieved in the field of non-empirical accurate quantum chemical calculations, such as density functional based symmetry adapted perturbation theory and diffusion quantum Monte Carlo calculations. Agreement of their results with the reference coupled cluster treatment at the complete basis set limit has established a consensus about the quality of the reference data and put accuracy assessment on firm ground. Availability of accurate reference data contributed a great deal to development of fast and reliable quantum mechanical methodologies. In the current review we encompass recent developments in the field of accurate reference quantum mechanical calculations, facilitate orientation among the quickly appearing treatments, and emphasize the vital importance of accurate reference calculations for development of model chemistries.
Zbořil, R.; Karlický, F.; Bourlinos, A. B.; Steriotis, T. A.; Stubos, A. K.; Georgakilas, V.; Šafářová, K.; Jančík, D.; Trapalis, C.; Otyepka, M. Graphene Fluoride: A Stable Stoichiometric Graphene Derivative and Its Chemical Conversion to Graphene, Small 2010, 6, 2885-2891. Link
Abstract: Stoichoimetric graphene fluoride monolayers are obtained in a single step by the liquid-phase exfoliation of graphite fluoride with sulfolane. Comparative quantum-mechanical calculations reveal that graphene fluoride is the most thermodynamically stable of five studied hypothetical graphene derivatives; graphane, graphene fluoride, bromide, chloride, and iodide. The graphene fluoride is transformed into graphene via graphene iodide, a spontaneously decomposing intermediate. The calculated bandgaps of graphene halides vary from zero for graphene bromide to 3.1 eV for graphene fluoride. It is possible to design the electronic properties of such two-dimensional crystals.
Dallas, P.; Tucek, J.; Jancik, D.; Kolar, M.; Panacek, A.; Zboril, R. Magnetically Controllable Silver Nanocomposite with Multifunctional Phosphotriazine Matrix and High Antimicrobial Activity, Adv. Funct. Mater. 2010, 20, 2347-2354. Link
Abstract: A recently developed multi-functional phosphotriazine-based polymer is used as a matrix for embedding γ-Fe2O3 nanoparticles as well as a suitable chemical template for surface modification with silver nanoparticles. For the primary magnetic modification, maghemite nanoparticles are surface modified with oleic acid in order to render them organophilic and to prevent the aggregation of the nanoparticles. This aggregation could occur as the polymer synthesis, based on reaction of phosphonitrilic chlorine and 1,4-phenylenediamine, takes place in toluene. The surface active amine units of the polymer structure enable the reduction of silver cations to silver nanoparticles, which are well attached and finely dispersed on its surface. The developed nanocomposite represents one of the few magnetically controllable antibacterial agents based on silver nanoparticles. Magnetic measurements reveal the completely suppressed interactions among maghemite nanoparticles because of their perfect surface coating with an organic surfactant and fine dispersion inside the polymer matrix. This magnetic nanocomposite exhibits a high antibacterial and antifungal activity as proven by tests with nine bacterial strains and four candida (yeast genus) species. For the majority of the tested species, the minimum-inhibition concentrations are below 100 mg L-1, which is comparable to their equivalent minimum-inhibition concentrations in colloidal silver systems.
Sivula, K.; Zboril, R.; Le Formal, F.; Robert, R.; Weidenkaff, A.; Tucek, J.; Frydrych, J.; Gratzel, M. Photoelectrochemical Water Splitting with Mesoporous Hematite Prepared by a Solution-Based Colloidal Approach, J. Am. Chem. Soc. 2010, 132, 7436-7444. Link
Abstract: Sustainable hydrogen production through photoelectrochemical water splitting using hematite (α-Fe2O3) is a promising approach for the chemical storage of solar energy, but is complicated by the material’s nonoptimal optoelectronic properties. Nanostructuring approaches have been shown to increase the performance of hematite, but the ideal nanostructure giving high efficiencies for all absorbed light wavelengths remains elusive. Here, we report for the first time mesoporous hematite photoelectodes prepared by a solution-based colloidal method which yield water-splitting photocurrents of 0.56 mA cm−2under standard conditions (AM 1.5G 100 mW cm−2, 1.23 V vs reversible hydrogen electrode, RHE) and over 1.0 mA cm−2 before the dark current onset (1.55 V vs RHE). The sintering temperature is found to increase the average particle size, and have a drastic effect on the photoactivity. X-ray photoelectron spectroscopy and magnetic measurements using a SQUID magnetometer link this effect to the diffusion and incorporation of dopant atoms from the transparent conducting substrate. In addition, examining the optical properties of the films reveals a considerable change in the absorption coefficient and onset properties, critical aspects for hematite as a solar energy converter, as a function of the sintering temperature. A detailed investigation into hematite’s crystal structure using powder X-ray diffraction with Rietveld refinement to account for these effects correlates an increase in a C3v-type crystal lattice distortion to the improved optical properties.
Nachtigallova, D.; Zeleny, T.; Ruckenbauer, M.; Muller, H.; Barbatti, M.; Hobza, P.; Lischka, H. Does Stacking Restrain the Photodynamics of Individual Nucleobases? J. Am. Chem. Soc. 2010, 132, 8261-8263. Link
Abstract: Nonadiabatic photodynamical simulations of 4-aminopyrimidine (4-APy) used as a model for adenine were performed by embedding it between two stacking methyl-guanine (mGua) molecules to determine the effect of spatial restrictions on the ultrafast photodeactivation mechanism of this nucleobase. A hybrid multiconfigurational ab initio/molecular mechanical approach in combination with surface hopping was used. During the dynamics the formation of a significant fraction of intrastrand hydrogen bonding from 4-APy to mGua above and below is observed. These findings show that this type of hydrogen bond may play an important role for the photodynamics within one DNA strand and that it should be of interest even in irregular segments of double stranded nucleic acids structures. The relaxation mechanism of internal conversion to the ground state is dominated by ring puckering, and an overall elongation of the lifetime of the embedded system by 20% as compared to the isolated 4-APy is computed.
2009
Herchel, R.; Šindelář, Z.; Trávníček, Z.; Zbořil, R.; Vančo, J. Novel 1D Chain Fe(III)-salen-like Complexes Involving Anionic Heterocyclic N-Donor Ligands. Synthesis, X-ray Structure, Magnetic, 57Fe Mössbauer, and Biological Activity Studies, Dalton Trans. 2009, 9870-9880. Link
Abstract: The iron(III) salen-type complexes [Fe(salen)(L)]n (1–6) involving heterocyclic N-donor ligands HL {HL = 1H-imidazole (Himz), 1H-tetrazol-5-amine (Hatz), 5-methyl-1H-tetrazole (Hmtz), 1H-benzimidazole (Hbimz), 1H-1,2,4-triazole (Htriz) and 1H-benzotriazole (Hbtriz)} have been prepared and characterised by elemental analysis, FT IR, CI mass and 57Fe Mössbauer spectroscopies, and variable temperature magnetic measurements. Single crystal X-ray analysis of [Fe(salen)(btriz)]n (6) revealed a 1D chain-polymeric structure of the complex with the btriz anion as a bridging ligand. Magnetic data for all complexes were fitted using Fisher’s model (for S = 5/2) and also using a heptanuclear closed ring model showing a weak antiferromagnetic interaction (J≈−1 to −2 cm−1), and moreover, molecule-based magnet properties have been observed in the case of [Fe(salen)(atz)]n (2). The exponential correlation between the magnetic properties (the isotropic exchange parameter J) and the basicity of the free ligands (Kb) has been found. The antiferromagnetic ordering as well as a moderate structural dissimilarity in the vicinity of iron atoms has been proved by the 57Fe Mössbauer low-temperature (2 K) in-field (7 T) experiments in the case of (2), in which two sextets with the line intensities (3/4/1/3/4/1) have been observed. The compounds have been tested for their SOD-like activity, DNA cleavage activity, and in vitro cytotoxicity against two human cancer cell lines: chronic myelogenous erythroleukemia (K562) and breast adenocarcinoma (MCF7). The best result regarding the cytotoxicity has been achieved for the complex of [Fe(salen)(atz)]n (2), where IC50 = 6.4 μM against K562.
Pól, J.; Vidová, V.; Kruppa,G.; Kobliha, V.; Novák, P.; Lemr, K.; Kotiaho, T.; Kostiainen, R.; Havlíček, V.; Volný, M. Automated Ambient Desorption−Ionization Platform for Surface Imaging Integrated with a Commercial Fourier Transform Ion Cyclotron Resonance Mass Spectrometer Anal. Chem. 2009, 20, 8479–8487. Link
Abstract:A fully automated atmospheric pressure ionization platform has been built and coupled with a commercial high-resolution Fourier transform ion cyclotron resonance mass spectrometer (FTICR-MS) instrument. The outstanding performance of this instrument allowed screening on the basis of exact masses in imaging mode. The main novel aspect was in the integration of the atmospheric pressure ionization imaging into the current software for matrix-assisted laser desorption ionization (MALDI) imaging, which allows the user of this commercial dual-source mass spectrometer to perform MALDI-MS and different ambient MS imaging from the same user interface and to utilize the same software tools. Desorption electrospray ionization (DESI) and desorption atmospheric pressure photoionization (DAPPI) were chosen to test the ambient surface imaging capabilities of this new ionization platform. Results of DESI imaging experiments performed on brain tissue sections are in agreement with previous MS imaging reports obtained by DESI imaging, but due to the high resolution and mass accuracy of the FTICR instrument it was possible to resolve several ions at the same nominal mass in the DESI-MS spectra of brain tissue. These isobaric interferences at low resolution are due to the overlap of ions from different lipid classes with different biological relevance. It was demonstrated that with the use of high-resolution MS fast imaging screening of lipids can be achieved without any preseparation steps. DAPPI, which is a relatively new and less developed ambient ionization technique compared to DESI, was used in imaging mode for the first time ever. It showed promise in imaging of phytocompounds from plant leaves, and selective ionization of a sterol lipid was achieved by DAPPI from a brain tissue sample.
Bourlinos, A. B.; Georgakilas, V.; Zboril, R.; Steriotis, T. A.; Stubos, A. K. Liquid-Phase Exfoliation of Graphite Towards Solubilized Graphenes, Small 2009, 5, 1841-1845. Link
Abstract:In summary, we have introduced a new series of solvents to extract solubilized graphenes from graphite powder. The first set comprises certain electron-deficient perfluorinated aromatic compounds, whereas the second set refers to the aromatic heterocycle of pyridine. Along with these liquids, some other dispersing media have been also listed. Depending on the solvent, graphite can be dispersed at variable concentrations and yields resulting in clear, stable colloids containing solubilized graphenes. We also demonstrated that the as-produced single layers can be easily converted into gold–graphene hybrids through wet chemistry. The solubility of graphite in such a wide range of solvents is believed to facilitate a broad spectrum of organic reactions with miscible reagents as well as solution processing of several polymer composites.
Kluchova, K.; Zboril, R.; Tucek, J.; Pecova, M.; Zajoncova, L.; Safarik, I.; Mashlan, M.; Markova, I.; Jancik, D.; Sebela, M.; Bartonkova, H.; Bellesi, V.; Novak, P.; Petridis, D. Superparamagnetic Maghemite Nanoparticles from Solid-State Synthesis – Their Functionalization Towards Peroral MRI Contrast Agent and Magnetic Carrier for Trypsin Immobilization, Biomaterials 2009, 30, 2855-2863. Link
Abstract: Nearly monodispersed superparamagnetic maghemite nanoparticles (15–20 nm) were prepared by a one-step thermal decomposition of iron(II) acetate in air at 400 °C. The presented synthetic route is simple, cost effective and allows to prepare the high-quality superparamagnetic particles in a large scale. The as-prepared particles were exploited for the development of magnetic nanocomposites with the possible applicability in medicine and biochemistry. For the purposes of the MRI diagnostics, the maghemite particles were simply dispersed in the bentonite matrix. The resulting nanocomposite represents very effective and cheap oral negative contrast agent for MRI of the gastrointestinal tract and reveals excellent contrast properties, fully comparable with those obtained for commercial contrast material. The results of the clinical research of this maghemite–bentonite contrast agent for imaging of the small bowel are discussed. For biochemical applications, the primary functionalization of the prepared maghemite nanoparticles with chitosan was performed. In this way, a highly efficient magnetic carrier for protein immobilization was obtained as demonstrated by conjugating thermostable raffinose-modified trypsin (RMT) using glutaraldehyde. The covalent conjugation resulted in a further increase in trypsin thermostability (T50 = 61 °C) and elimination of its autolysis. Consequently, the immobilization of RMT allowed fast in-solution digestion of proteins and their identification by MALDI–TOF mass spectrometry.
Pavlova, M.; Klvana, M.; Prokop, Z.; Chaloupkova, R.; Banas, P.; Otyepka, M.; Wade, R. C.; Tsuda, M.; Nagata, Y.; Damborsky, J. Redesigning Dehalogenase Access Tunnels as a Strategy for Degrading an Anthropogenic Substrate, Nature Chem. Biol.2009, 5, 727-733. Link
Abstract: Engineering enzymes to degrade anthropogenic compounds efficiently is challenging. We obtained Rhodococcus rhodochrous haloalkane dehalogenase mutants with up to 32-fold higher activity than wild type toward the toxic, recalcitrant anthropogenic compound 1,2,3-trichloropropane (TCP) using a new strategy. We identified key residues in access tunnels connecting the buried active site with bulk solvent by rational design and randomized them by directed evolution. The most active mutant has large aromatic residues at two out of three randomized positions and two positions modified by site-directed mutagenesis. These changes apparently enhance activity with TCP by decreasing accessibility of the active site for water molecules, thereby promoting activated complex formation. Kinetic analyses confirmed that the mutations improved carbon-halogen bond cleavage and shifted the rate-limiting step to the release of products. Engineering access tunnels by combining computer-assisted protein design with directed evolution may be a valuable strategy for refining catalytic properties of enzymes with buried active sites.
Panacek, A.; Kolar, M.; Vecerova, R.; Prucek, R.; Soukupova, J.; Krystof, V.; Hamal, P.; Zboril, R.; Kvitek, L. Antifungal Activity of Silver Nanoparticles Against Candida spp, Biomaterials 2009, 30, 6333-6340. Link
Abstract: The antifungal activity of the silver nanoparticles (NPs) prepared by the modified Tollens process was evaluated for pathogenic Candida spp. by means of the determination of the minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC), and the time-dependency of yeasts growth inhibition. Simultaneously the cytotoxicity of the silver NPs to human fibroblasts was determined. The silver NPs exhibited inhibitory effect against the tested yeasts at the concentration as low as 0.21 mg/L of Ag. The inhibitory effect of silver NPs was enhanced through their stabilization and the lowest MIC equal to 0.05 mg/L was determined for silver NPs stabilized by sodium dodecyl sulfate against Candida albicans II. The obtained MICs of the silver NPs and especially of the stabilized silver NPs were comparable and in some cases even better than MICs of the conventional antifungal agents determined by E-test. The silver NPs effectively inhibited the growth of the tested yeasts at the concentrations below their cytotoxic limit against the tested human fibroblasts determined at a concentration equal to 30 mg/L of Ag. In contrast, ionic silver inhibited the growth of the tested yeasts at the concentrations comparable to the cytotoxic level (approx. 1 mg/L) of ionic silver against the tested human fibroblasts.
Peřina, Jr., J.; Lukš, A.; Haderka, O.; Scalora, M. Surface Spontaneous Parametric Down-Conversion, Phys. Rev. Lett. 2009, 103, 063902-1-063902-4. Link
Abstract: Surface spontaneous parametric down-conversion is predicted as a consequence of continuity requirements for electric- and magnetic-field amplitudes at a discontinuity of χ(2) nonlinearity. A generalization of the usual two-photon spectral amplitude is suggested to describe this effect. Examples of nonlinear layered structures and periodically poled nonlinear crystals show that surface contributions to spontaneous down-conversion can be important.
2008
Cerny, J.; Kabelac, M.; Hobza, P.; Double-Helical -> Ladder Structural Transition in the B-DNA is Induced by a Loss of Dispersion Energy, J. Am. Chem. Soc. 2008, 130, 16055-16059. Link
Abstract: The role of the dispersion energy and electrostatic energy on the geometry and stability of theB-DNA helix was investigated. Both molecular dynamics simulations with empirical force field and hybridquantum mechanical/molecular mechanics molecular dynamics simulations, where the dispersion orelectrostatics term is suppressed/increased, on the one hand and an ab initio minimization procedure onthe other have shown that the lack of the dispersion term leads to an increase of the vertical separation ofthe bases as well as to a loss of helicity, thus resulting in a ladder-like structure. A decrease of theelectrostatic term produces a separation of the DNA strands. The biological consequences of bothelectrostatic and dispersion forces in DNA are enormous, and without either of them, DNA would becomeunstable and unable to provide the storage and transfer of genetic information.
Vančo, J.; Marek, J.; Trávníček, Z.; Račanská, E.; Muselík, J.; Švajlenová, O. Synthesis, Structural Characterization, Antiradical and Antidiabetic Activities of Copper(II) and Zinc(II) Schiff Base Complexes Derived from Salicylaldehyde and β-Alanine, J. Inorg. Biochem. 2008, 102, 595-605. Link
Abstract: A series of copper(II) and zinc(II) complexes involving a tridentate O,N,O’-donor Schiff base derived from salicylaldehyde and β-alanine {i.e. N-salicylidene-β-alanine(2-), (L)}, having the composition [Cu2(L)2(H2O)]·H2O (1), [Cu(L)(H2O)]n (2), and [Zn(L)(H2O)]n (3), have been prepared and characterized by elemental analyses, UV–visible (UV–VIS), FT-IR and ESI-MS spectra, and thermal analyses. Complexes 1 and 2 have been investigated by single crystal X-ray analysis and also by temperature dependent magnetic susceptibility measurements (294–80 K). All prepared complexes have been evaluated by the antiperoxynitrite activity assay and alloxan-induced diabetes model. The significant antioxidant and antidiabetic activities have been found in the case of both copper(II) complexes 1 and 2. In spite of first two complexes, the zinc(II) complex 3, as well as the potassium salt of the ligand (KHL) showed only insignificant protective effect against the tyrosine nitration in vitro.
Trávníček, Z.; Mikulík, J.; Čajan, M.; Zbořil, R.; Popa, I. Novel iron complexes bearing N6-substituted adenosine derivatives: Synthesis, magnetic, 57Fe Mössbauer, DFT, and in vitro cytotoxicity studies, Bioorg. Med. Chem. 2008, 16, 8719-8728.Link
Abstract: Iron complexes (1–7) involving N6-benzyladenosine derivatives of the predominant composition [Fe(Ln)Cl3] · H2O {where L1 = N6-(2-fluorobenzyl)adenosine (1), L2 = N6-(4-fluorobenzyl)adenosine (2), L3 = N6-(2-trifluoromethylbenzyl)adenosine (3), L4 = N6-(3-trifluoromethylbenzyl)adenosine (4), L5 = N6-(4-trifluoromethylbenzyl)adenosine (5), L6 = N6-(4-trifluoromethoxybenzyl)adenosine (6), and L7 = N6-(4-chlorobenzyl)adenosine (7)} have been synthesized. The compounds have been characterized by elemental analysis, variable-temperature and in-field 57Fe Mössbauer, ES+ MS, FTIR, 1H and 13C NMR spectroscopies, magnetochemical and conductivity measurements, thermal (TGA/DSC/DTA) analyses, and DFT calculations. It has been found that the organic molecule is coordinated to iron via N7 atom of the appropriate adenosine derivative and the products are represented by mixtures of complexes with various iron oxidation (FeIII/FeII) and spin states (S = 5/2, 4/2, 3/2, 2/2) and geometries (tetrahedral or trigonal bipyramidal). It is caused by the fact that partial redox processes proceed during the reactions due to the presence of a ribose moiety, which is oxidized to the corresponding 5′-ribotic acid, and simultaneously, a portion of FeIII cations is reduced to FeII ones. Moreover, a significant effect of crystal water molecules on stereochemistry, and hence, on magnetic and spectral properties of the prepared complexes has been found. The compounds have been tested for their in vitro cytotoxicity against the following human cancer cell lines: malignant melanoma (G-361), osteogenic sarcoma (HOS), chronic myelogenous leukemia (K-562), and breast adenocarcinoma (MCF-7). The most important results have been obtained for complex 2 with IC50 values 8–16 μM against HOS, K-562, and MCF-7 cell lines, and for complex 6 with IC50 value 4 μM against MCF-7 cell line.
Dvořák, Z.; Vrzal, R.; Henklová, P.; Jančová, P.; Anzenbacherová, E.; Maurel, P.; Švecová, L.; Pavek, P.; Ehrmann, J.; Havlík, R.; Bednář, P.; Lemr, K.; Ulrichová, J. JNK Inhibitor SP600125 is a Partial Agonist of Human Aryl Hydrocarbon Receptor and Induces CYP1A1 and CYP1A2 Genes in Primary Human Hepatocytes, Biochem. Pharmacol. 2008, 75, 580-588. Link
Abstract: SP600125, a specific inhibitor of c-Jun-N-Terminal kinase (JNK), was reported as a ligand and antagonist of aryl hydrocarbon receptor (AhR) [Joiakim A, Mathieu PA, Palermo C, Gasiewicz TA, Reiners Jr JJ. The Jun N terminal kinase inhibitor SP600125 is a ligand and antagonist of the aryl hydrocarbon receptor. Drug Metab Dispos 2003;31(11):1279–82]. Here we show that SP600125 is not an antagonist but a partial agonist of human AhR. SP600125 significantly induced CYP1A1 and CYP1A2 mRNAs in primary human hepatocytes and CYP1A1 mRNA in human hepatoma cells HepG2. This effect was abolished by resveratrol, an antagonist of AhR. Consistent with the recent report, SP600125 dose-dependently inhibited CYP1A1 and CYP1A2 genes induction by a prototype AhR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in human hepatocytes. Moreover, SP600125 displayed typical behavior of a partial agonist in HepG2 cells transiently transfected with a reporter plasmid containing two inverted repeats of the dioxin responsive element or with a plasmid containing 5′-flanking region of human CYP1A1 gene. SP600125 transactivated the reporter plasmids with EC50 of 0.005 and 1.89 μM, respectively. On the other hand, TCDD-dependent transactivation of the reporter plasmids was inhibited by SP600125 with IC50 values of 1.54 and 2.63 μM, respectively. We also tested, whether the effects of SP600125 are due to metabolism. Using liquid chromatography/mass spectrometry approach, we observed formation of two minor monohydroxylated metabolites of SP600125 in human hepatocytes, human liver microsomes but not in HepG2 cells. These data imply that biotransformation is not responsible for the effects of SP600125 on AhR signaling. In conclusion, we demonstrate that SP600125 is a partial agonist of human AhR, which induces CYP1A genes.
2007
The Pierre Auger Collaboration, Correlation of the Highest-Energy Cosmic Rays with Nearby Extragalactic Objects, Science 2007, 318, 938-943. Link
Abstract: Using data collected at the Pierre Auger Observatory during the past 3.7 years, we demonstrated a correlation between the arrival directions of cosmic rays with energy above 6 × 1019 electron volts and the positions of active galactic nuclei (AGN) lying within 75 megaparsecs. We rejected the hypothesis of an isotropic distribution of these cosmic rays with at least a 99% confidence level from a prescribed a priori test. The correlation we observed is compatible with the hypothesis that the highest-energy particles originate from nearby extragalactic sources whose flux has not been substantially reduced by interaction with the cosmic background radiation. AGN or objects having a similar spatial distribution are possible sources.
Hermanek, M.; Zboril, R.; Medrik, I.; Pechousek, J.; Gregor, C. Catalytic Efficiency of Iron(III) Oxides in Decomposition of Hydrogen Peroxide: Competition between the Surface Area and Crystallinity of Nanoparticles, J. Am. Chem. Soc. 2007, 129, 10929-10936. Link
Abstract: Various iron(III) oxide catalysts were prepared by controlled decomposition of a narrow layer (ca. 1 mm) of iron(II) oxalate dihydrate, FeC2O4·2H2O, in air at the minimum conversion temperature of 175 °C. This thermally induced solid-state process allows for simple synthesis of amorphous Fe2O3 nanoparticles and their controlled one-step crystallization to hematite (α-Fe2O3). Thus, nanopowders differing in surface area and particle crystallinity can be produced depending on the reaction time. The phase composition of iron(III) oxides was monitored by XRD and 57Fe Mössbauer spectroscopy including in-field measurements, providing information on the relative contents of amorphous and crystalline phases. The gradual changes in particle size and surface area accompanying crystallization were evaluated by HRTEM and BET analysis, respectively. The catalytic efficiency of the synthesized nanoparticles was tested by tracking the decomposition of hydrogen peroxide. The obtained kinetic data gave an unconventional nonmonotone dependence of the rate constant on the surface area of the samples. The amorphous nanopowder with the largest surface area of 401 m2 g-1 revealed the lowest catalytic efficiency, while the highest efficiency was achieved with the sample having a significantly lower surface area, 337 m2 g-1, exhibiting a prevailing content of crystalline α-Fe2O3 phase. The obtained rate constant, 26.4 × 10-3 min-1 (g/L)-1, is currently the highest value published. The observed rare catalytic phenomenon, where the particle crystallinity prevails over the surface area effects, is discussed with respect to other processes of heterogeneous catalysis.
Cvek, B.; Dvořák, Z. Targeting of Nuclear Factor-κB and Proteasome by Dithiocarbamate Complexes with Metals, Curr. Pharm. Des. 2007, 13, 3155-3167. Link
Abstract: Dithiocarbamates and their complexes with transition metals have been used as common pesticides, vulcanizing or analytical agents for decades. These compounds are one of the most reported inhibitors of nuclear factor-κB (NF-κB) signaling cascade. Recently, it has been found that dithiocarbamates are very potent inhibitors of proteasome. NF-κB plays a central role in the immune system and is described as a major actor in many of human cancers mainly because of its protective effects against apoptosis. Molecular mechanisms involved in regulation and function of NF-κB pathway have been elucidated recently. In particular, pivotal zinc containing proteins that alter NF-κB signal transduction were recognized. Additionally, proteasome system was found to be a key player in NF-κB pathway and is an attractive target for anticancer drug development. Collectively, the capability of dithiocarbamates to inhibit NF-κB and proteasome makes these compounds promising anticancer agents. This review focuses on the biological activity of dithiocarbamate coordination compounds with regard to their possible molecular targets in NF-κB signaling and proteasome (JAMM domain proteins). Future research should aim to find the most suitable dithiocarbamate coordination compounds for treatment of cancer and other diseases.
2006
Panacek, A.; Kvitek, L.; Prucek, R.; Kolar, M.; Vecerova, R.; Pizurova, N.; Sharma, V. K.; Nevecna, T.; Zboril, R. Silver Colloid Nanoparticles: Synthesis, Characterization, and Their Antibacterial Activity, J. Phys. Chem. B 2006, 110, 16248-16253. Link
Abstract: A one-step simple synthesis of silver colloid nanoparticles with controllable sizes is presented. In this synthesis, reduction of [Ag(NH3)2]+ complex cation by four saccharides was performed. Four saccharides were used: two monosaccharides (glucose and galactose) and two disaccharides (maltose and lactose). The syntheses performed at various ammonia concentrations (0.005−0.20 mol L-1) and pH conditions (11.5−13.0) produced a wide range of particle sizes (25−450 nm) with narrow size distributions, especially at the lowest ammonia concentrations. The average size, size distribution, morphology, and structure of particles were determined by dynamic light scattering (DLS), transmission electron microscopy (TEM), and UV/Visible absorption spectrophotometry. The influence of the saccharide structure (monosacharides versus disaccharides) on the size of silver particles is briefly discussed. The reduction of [Ag(NH3)2]+ by maltose produced silver particles with a narrow size distribution with an average size of 25 nm, which showed high antimicrobial and bactericidal activity against Gram-positive and Gram-negative bacteria, including highly multiresistant strains such as methicillin-resistant Staphylococcus aureus. Antibacterial activity of silver nanoparticles was found to be dependent on the size of silver particles. A very low concentration of silver (as low as 1.69 μg/mL Ag) gave antibacterial performance.
Petrek, M.; Otyepka, M.; Banas, P.; Kosinova, P.; Koca, J.; Damborsky, J. CAVER: A new tool to explore routes from protein clefts, pockets and cavities, BMC Bioinformatics, 2006, 7 , 316. Link
Abstract: The main aim of this study was to develop and implement an algorithm for the rapid, accurate and automated identification of paths leading from buried protein clefts, pockets and cavities in dynamic and static protein structures to the outside solvent. Results: The algorithm to perform a skeleton search was based on a reciprocal distance function grid that was developed and implemented for the CAVER program. The program identifies and visualizes routes from the interior of the protein to the bulk solvent. CAVER was primarily developed for proteins, but the algorithm is sufficiently robust to allow the analysis of any molecular system, including nucleic acids or inorganic material. Calculations can be performed using discrete structures from crystallographic analysis and NMR experiments as well as with trajectories from molecular dynamics simulations. The fully functional program is available as a stand-alone version and as plug-in for the molecular modeling program PyMol. Additionally, selected functions are accessible in an online version. Conclusion: The algorithm developed automatically finds the path from a starting point located within the interior of a protein. The algorithm is sufficiently rapid and robust to enable routine analysis of molecular dynamics trajectories containing thousands of snapshots. The algorithm is based on reciprocal metrics and provides an easy method to find a centerline, i.e. the spine, of complicated objects such as a protein tunnel. It can also be applied to many other molecules. CAVER is freely available from the web site Caver.Despite a large success of CAVER software, it has been outperformed by MOLE, which is more robust and quicker.
Trávníček, Z.; Kryštof, V.; Šipl, M. Zinc(II) complexes with potent cyclin-dependent kinase inhibitors derived from 6-benzylaminopurine: Synthesis, characterization, X-ray structures and biological activity. J. Inorg. Biochem., 2006, 2, 214-225. Link
Abstract: The synthesis, characterization and biological activity of the first zinc(II) complexes with potent inhibitors of cyclin-dependent kinases (CDKs) derived from 6-benzylaminopurine are described. Based on the results following from elemental analyses, infrared, NMR and ES+MS (electrospray mass spectra in the positive ion mode) spectroscopies, conductivity data, thermal analysis and X-ray structures, the tetrahedral Zn(II) complexes of the compositions [Zn(Olo)Cl(2)](n) (1), [Zn(iprOlo)Cl(2)](n) (2), [Zn(BohH(+))Cl(3)] x H(2)O (3) and [Zn(iprOloH(+))Cl(3)] x H(2)O (4) have been prepared, where Olo=2-(2-hydroxyethylamino)-6-benzylamino-9-methylpurine (Olomoucine), iprOlo=2-(2-hydroxyethylamino)-6-benzylamino-9-isopropylpurine (i-propyl-Olomoucine), Boh=2-(3-hydroxypropylamino)-6-benzylamino-9-isopropylpurine (Bohemine). The 1D-polymeric chain structure for [Zn(Olo)Cl(2)](n) (1) as well as the monomeric one for [Zn(BohH(+))Cl(3)] x H(2)O (3) and [Zn(iprOloH(+))Cl(3)] x H(2)O (4) have been revealed unambiguously by single crystal X-ray analyses. The 1D-polymeric chain of 1 consists of Zn(Olo)Cl(2) monomeric units in which the Zn(II) ion is coordinated by two chlorine atoms and one oxygen atom of the 2-hydroxyethylamino group of Olomoucine. The next monomeric unit is bonded to Zn(II) through the N7 atom of a purine ring. Thus, each of Zn(II) ions is tetrahedrally coordinated and a ZnCl(2)NO chromophore occurs in the complex 1. The complexes 3 and 4 are mononuclear species with a distorted tetrahedral arrangement of donor atoms around the Zn(II) ion with a ZnCl(3)N chromophore. The corresponding CDK inhibitor, i.e., both Boh and iprOlo, is coordinated to Zn(II) via the N7 atom of the purine ring in 3 and 4. The cytotoxicity of the zinc(II) complexes against human melanoma, sarcoma, leukaemia and carcinoma cell lines has been determined as well as the inhibition of the CDK2/cyclin E kinase. A relationship between the structure and biological activity of the complexes is also discussed.