Jaroslav V. Burda

Density functional study of structural and electronic properties of bimetallic silver–gold clusters: Comparison with pure gold and silver clusters

Bimetallic silver–gold clusters offer an excellent opportunity to study changes in metallic versus “ionic” properties involving charge transfer as a function of the size and the composition, particularly when compared to pure silver and gold clusters. We have determined structures, ionization potentials, and vertical detachment energies for neutral and charged bimetallic AgmAun [3⩽(m+n)⩽5] clusters. Calculated VDE values compare well with available experimental data. In the stable structures of these clusters Au atoms assume positions which favor the charge transfer from Ag atoms. Heteronuclear bonding is usually preferred to homonuclear bonding in clusters with equal numbers of hetero atoms. In fact, stable structures of neutral Ag2Au2, Ag3Au3, and Ag4Au4 clusters are characterized by the maximum number of hetero bonds and peripheral positions of Au atoms. Bimetallic tetramer as well as hexamer are planar and have common structural properties with corresponding one-component systems, while Ag4Au4 and Ag8...

Anthracyclines and ellipticines as DNA-damaging anticancer drugs: Recent advances

Over the past forty years, anthracyclines and ellipticines have attracted attention as promising cytostatics. In this review, we focus on their mechanisms of cytoxicity, DNA-damaging effects and adverse side-effects. We also summarize ways to enhance the therapeutic effects of these drugs together with a decrease in their adverse effects. Current drug design strategies are focused on drug bioavailability and their tissue targeting, whereas drug delivery to specific intracellular compartments is rarely addressed. Therefore, therapies utilizing the antineoplastic activities of anthracyclines and ellipticines combined with novel strategies such as nanotechnologies for safer drug delivery, as well as strategies based on gene therapy, could significantly contribute to medical practice.

Hydration of cis- and trans-platin: A pseudopotential treatment in the frame of a G3-type theory for platinum complexes

Hydration of selected platinum complexes [PtCl42−, Pt(NH3)42+, and cis- and trans-platin–PtCl2(NH3)2] have been studied. Up to two solvent molecules have been considered to replace the ligands. In order to be able to draw conclusions about pH changes in the course of the hydration process, both H2O and OH− species were considered in the solvating process. The modified Gaussian 3 theory was adapted for the pseudopotential treatment of platinum complexes. Since a heavy element was present in the complexes, an additional stabilization due to the spin–orbit coupling and core-polarization potentials have been evaluated above the scheme of a G3 treatment. This spin–orbit coupling stabilization amounts to 2–5 kcal/mol but does not qualitatively change the hydration preferences. In accord with the experiment, neutral Pt(NH3)2(OH)2 was found to be the most stable complex for hydration of both cis- and trans-platin.

Hydration process as an activation of trans- and cisplatin complexes in anticancer treatment. DFT and ab initio computational study of thermodynamic and kinetic parameters.

The thermodynamic and kinetic aspects of hydration reactions of cis‐/transplatin were explored. The polarizable continuum model was used for estimation of solvent effects. Using the B3LYP/6‐31+G(d) method, the structures were optimized and vibrational frequencies estimated. Interaction energies and activation barriers were determined at the CCSD(T)/6‐31++G(d,p) level within the COSMO approach. An associative mechanism was assumed with a trigonal‐bipyramidal structure of the transition state. Within the applied model, all the hydration reactions are slightly endothermic. The Gibbs energies of cisplatin hydration amount to 7.0 and 14.2 kcal/mol for the chloride and ammonium replacement, respectively. Analogous values for the transplatin reactions are 6.8 and 11.9 kcal/mol. The determined rate constants are by several (three to four) orders of magnitude larger for the dechlorination process than for deammination. The cisplatin dechlorination rate constant was established as 1.3 · 10−4 s−1 in excellent accord with the experiment.

Activation barriers and rate constants for hydration of platinum and palladium square-planar complexes: An ab initio study

In the present work, an ab initio study on hydration (a metal-ligand replacement by water molecule or OH- group) of cis- and transplatin and their palladium analogs was performed within a neutral pseudomolecule approach (e.g., metal-complex+water as reactant complex). Subsequent replacement of the second ligand was considered. Optimizations were performed at the MP2/6-31+G(d) level with single-point energy evaluation using the CCSD(T)/6-31++G(d,p) approach. For the obtained structures of reactants, transition states (TSs), and products, both thermodynamic (reaction energies and Gibbs energies) and kinetic (rate constants) characteristics were estimated. It was found that all the hydration processes are mildly endothermic reactions-in the first step they require 8.7 and 10.2 kcal/mol for ammonium and chloride replacement in cisplatin and 13.8 and 17.8 kcal/mol in the transplatin case, respectively. Corresponding energies for cispalladium amount to 5.2 and 9.8 kcal/mol, and 11.0 and 17.7 kcal/mol for transpalladium. Based on vibrational analyses at MP2/6-31+G(d) level, transition state theory rate constants were computed for all the hydration reactions. A qualitative agreement between the predicted and known experimental data was achieved. It was also found that the close similarities in reaction thermodynamics of both Pd(II) and Pt(II) complexes (average difference for all the hydration reactions are approximately 1.8 kcal/mol) do not correspond to the TS characteristics. The TS energies for examined Pd(II) complexes are about 9.7 kcal/mol lower in comparison with the Pt analogs. This leads to 10(6) times faster reaction course in the Pd cases. This is by 1 or 2 orders of magnitude more than the results based on experimental measurements.

Cisplatin interaction with cysteine and methionine in aqueous solution: computational DFT/PCM study.

In this paper we explore cisplatin interactions with sulfur-containing amino acids in a polarizable continuum model. Two cisplatin hydrated complexes were considered as reactants (chloro complex, cis-[Pt(NH3)2Cl(H2O)]+; hydroxo complex, cis-[Pt(NH3)2(OH)(H2O)]+). We considered the following reaction mechanism: first step, substitution of the aqua ligand by amino acid; second step, dissociative chelate formation. For the optimized complex (at the B3LYP/6-31+G(d)/COSMO level), the energy profile was determined using the B3LYP/6-311++G(2df,2pd) level and two different PCM models-COSMO and UAKS/DPCM methods which were adapted for use on transition metal complexes. The results show thermodynamic preference for bonding by cysteine sulfur followed by the amino group nitrogen, methionine thioether sulfur, and carboxyl-group oxygen. Methionine slightly prefers the Pt-N(Met) coordination in the chloro complex, but in the hydroxo complex it prefers the Pt-S(Met) coordination. A similar trend follows from the bonding energies: BE(Pt-S(Cys)) = 80.8 kcal/mol and BE(Pt-N(Met)) = 76 kcal/mol. According to the experimental observations, the most stable structures found are kappa2(S,N) chelates. In the case of methionine, the same thermodynamic stability is predicted also for the kappa2(N,O) chelate. This differs from the gas-phase results, where kappa2(S,N) and even kappa2(S,O) were found to be more stable than kappa2(N,O) complex.

NMR spectroscopic detection of chirality and enantiopurity in referenced systems without formation of diastereomers.

Enantiomeric excess of chiral compounds is a key parameter that determines their activity or therapeutic action. The current paradigm for rapid measurement of enantiomeric excess using NMR is based on the formation of diastereomeric complexes between the chiral analyte and a chiral resolving agent, leading to (at least) two species with no symmetry relationship. Here we report an effective method of enantiomeric excess determination using a symmetrical achiral molecule as the resolving agent, which is based on the complexation with analyte (in the fast exchange regime) without the formation of diastereomers. The use of N,N′-disubstituted oxoporphyrinogen as the resolving agent makes this novel method extremely versatile, and appropriate for various chiral analytes including carboxylic acids, esters, alcohols and protected amino acids using the same achiral molecule. The model of sensing mechanism exhibits a fundamental linear response between enantiomeric excess and the observed magnitude of induced chemical shift non-equivalence in the 1H NMR spectra.

The structure of metallo-DNA with consecutive thymine–HgII–thymine base pairs explains positive entropy for the metallo base pair formation

We have determined the three-dimensional (3D) structure of DNA duplex that includes tandem HgII-mediated T–T base pairs (thymine–HgII–thymine, T–HgII–T) with NMR spectroscopy in solution. This is the first 3D structure of metallo-DNA (covalently metallated DNA) composed exclusively of ‘NATURAL’ bases. The T–HgII–T base pairs whose chemical structure was determined with the 15N NMR spectroscopy were well accommodated in a B-form double helix, mimicking normal Watson–Crick base pairs. The Hg atoms aligned along DNA helical axis were shielded from the bulk water. The complete dehydration of Hg atoms inside DNA explained the positive reaction entropy (ΔS) for the T–HgII–T base pair formation. The positive ΔS value arises owing to the HgII dehydration, which was approved with the 3D structure. The 3D structure explained extraordinary affinity of thymine towards HgII and revealed arrangement of T–HgII–T base pairs in metallo-DNA.

Metal ions in non-complementary DNA base pairs: an ab initio study of Cu(I), Ag(I), and Au(I) complexes with the cytosine-adenine base pair

Abstract Ab initio calculations have been carried out to characterize the structure and energetics of a silver(I) complex with the cytosine-adenine DNA base pair and an aqua ligand in the coordination sphere of Ag. In addition, we have also studied analogous complexes with Cu(I) and Au(I), and structures in which adenine has been replaced by purine in order to investigate the structural role of the adenine amino group. The calculations revealed that all metal-modified structures are dominated by the metal-base interactions, while the water-metal ion interaction and many-body interligand repulsion are less important contributions. Nevertheless, the structural role of the water molecule in the complex is quite apparent and in agreement with an earlier crystallographic study. The metal-modified base pairs exhibit large conformational flexibility toward out-of-plane motions (propeller twist and buckle), comparable or, in some cases, even larger than that observed in the base pairs without metal ions. All structures have been optimized within the Hartree-Fock approximation, while interaction energies were evaluated with the inclusion of electron correlation.

The trans effect in square‐planar platinum(II) complexes—A density functional study

The mechanism of substitution water exchange reactions in square planar trans‐Pt[(NH3)2T(H2O)]n+ complexes is studied (TH2O, NH3, OH−, F−, Cl−, Br−, H2S, CH3S−, SCN−, CN−, PH3, CO, CH3−, H−, C2H4). The trans effect is explained in terms of σ‐donation and π‐back‐donation whose relative strengths are quantified by the changes of electron occupations of 5d platinum atomic orbitals. The σ‐donation strength is linearly correlated with the PtH2O (leaving ligand) bond length (trans influence). The kinetic trans effect strength correlates proportionally with the σ‐donation ability of the trans‐ligand except the ligands with strong π‐back‐donation ability that stabilizes transition state structure. The σ‐donation ability of the ligand is dependent on the σ‐donation strength of the ligand in the trans position. Therefore the trans effect caused by σ‐donation can be understood as a competition between the trans‐ligands for the opportunity to donate electron density to the central Pt(II) atom. The influence of the trans effect on the reaction mechanism is also shown. For ligands with a very strong σ‐donation (e.g. CH3− and H−), the substitution proceeds by a dissociative interchange (Id) mechanism. Ligands with strong π‐back donation ability (e.g. C2H4) stabilize the pentacoordinated intermediate and the substitution proceeds by a two step associative mechanism. For ligands with weak σ‐donation and π‐back‐donation abilities, the highest activation barriers have to be overcome and substitutions can be described by an associative interchange (Ia) mechanism. The results are supported by the energy decomposition and the natural orbital analysis.