Judit E. Šponer

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.

Nature and magnitude of aromatic base stacking in DNA and RNA: Quantum chemistry, molecular mechanics, and experiment

Base stacking is a major interaction shaping up and stabilizing nucleic acids. During the last decades, base stacking has been extensively studied by experimental and theoretical methods. Advanced quantum-chemical calculations clarified that base stacking is a common interaction, which in the first approximation can be described as combination of the three most basic contributions to molecular interactions, namely, electrostatic interaction, London dispersion attraction and short-range repulsion. There is not any specific π-π energy term associated with the delocalized π electrons of the aromatic rings that cannot be described by the mentioned contributions. The base stacking can be rather reasonably approximated by simple molecular simulation methods based on well-calibrated common force fields although the force fields do not include nonadditivity of stacking, anisotropy of dispersion interactions, and some other effects. However, description of stacking association in condensed phase and understanding of the stacking role in biomolecules remain a difficult problem, as the net base stacking forces always act in a complex and context-specific environment. Moreover, the stacking forces are balanced with many other energy contributions. Differences in definition of stacking in experimental and theoretical studies are explained.

High-energy chemistry of formamide: A unified mechanism of nucleobase formation

Significance This paper addresses one of the central problems of the origin of life research, i.e., the scenario suggesting extraterrestrial impact as the source of biogenic molecules. Likewise, the results might be relevant in the search of biogenic molecules in the universe. The work is therefore highly actual and interdisciplinary. It could be interesting for a very broad readership, from physical and organic chemists to synthetic biologists and specialists in astrobiology. The coincidence of the Late Heavy Bombardment (LHB) period and the emergence of terrestrial life about 4 billion years ago suggest that extraterrestrial impacts could contribute to the synthesis of the building blocks of the first life-giving molecules. We simulated the high-energy synthesis of nucleobases from formamide during the impact of an extraterrestrial body. A high-power laser has been used to induce the dielectric breakdown of the plasma produced by the impact. The results demonstrate that the initial dissociation of the formamide molecule could produce a large amount of highly reactive CN and NH radicals, which could further react with formamide to produce adenine, guanine, cytosine, and uracil. Based on GC-MS, high-resolution FTIR spectroscopic results, as well as theoretical calculations, we present a comprehensive mechanistic model, which accounts for all steps taking place in the studied impact chemistry. Our findings thus demonstrate that extraterrestrial impacts, which were one order of magnitude more abundant during the LHB period than before and after, could not only destroy the existing ancient life forms, but could also contribute to the creation of biogenic molecules.

The DNA and RNA sugar–phosphate backbone emerges as the key player. An overview of quantum-chemical, structural biology and simulation studies

Knowledge of geometrical and physico-chemical properties of the sugar-phosphate backbone substantially contributes to the comprehension of the structural dynamics, function and evolution of nucleic acids. We provide a side by side overview of structural biology/bioinformatics, quantum chemical and molecular mechanical/simulation studies of the nucleic acids backbone. We highlight main features, advantages and limitations of these techniques, with a special emphasis given to their synergy. The present status of the research is then illustrated by selected examples which include classification of DNA and RNA backbone families, benchmark structure-energy quantum chemical calculations, parameterization of the dihedral space of simulation force fields, incorporation of arsenate into DNA, sugar-phosphate backbone self-cleavage in small RNA enzymes, and intricate geometries of the backbone in recurrent RNA building blocks. Although not apparent from the current literature showing limited overlaps between the QM, simulation and bioinformatics studies of the nucleic acids backbone, there in fact should be a major cooperative interaction between these three approaches in studies of the sugar-phosphate backbone.

Coordination and properties of cobalt in the molecular sieves CoAPO-5 and -11

Abstract Diffuse reflectance electronic spectra have been utilized to investigate the local geometry of cobalt centers substituted in the three-dimensional framework of CoAPO-5 and -11 molecular sieves. Structural changes induced by calcination in an oxidative atmosphere, evacuation and hydrogen treatment, as well as by adsorption of amines and water are discussed in terms of the steric conditions of cobalt incorporation in the aluminophosphate matrix. We suggest a template–framework interaction between the framework cobalt centers and neutral amine-type templates as an alternative stabilizing effect in the as-synthesized samples. Spectral changes observed after calcination in oxygen are interpreted as distortion-induced charge transfer effects without oxidation of the divalent cobalt ions. Formation of oxygen vacancies in the close vicinity of the cobalt sites is proposed to explain the adsorption properties of the framework cobalt centers.

Quantum Chemical Studies of Nucleic Acids: Can We Construct a Bridge to the RNA Structural Biology and Bioinformatics Communities?

In this feature article, we provide a side-by-side introduction for two research fields: quantum chemical calculations of molecular interaction in nucleic acids and RNA structural bioinformatics. Our main aim is to demonstrate that these research areas, while largely separated in contemporary literature, have substantial potential to complement each other that could significantly contribute to our understanding of the exciting world of nucleic acids. We identify research questions amenable to the combined application of modern ab initio methods and bioinformatics analysis of experimental structures while also assessing the limitations of these approaches. The ultimate aim is to attain valuable physicochemical insights regarding the nature of the fundamental molecular interactions and how they shape RNA structures, dynamics, function, and evolution.

HYDROGEN-BONDED TRIMERS OF DNA BASES AND THEIR INTERACTION WITH METAL CATIONS : AB INITIO QUANTUM-CHEMICAL AND EMPIRICAL POTENTIAL STUDY

Neutral (G.GC, A.AT, G.AT, T.AT, and C(imino).GC) and protonated (CH+.GC and AH+.GC) hydrogen-bonded trimers of nucleic acid bases were characterized by ab initio methods with the inclusion of electron correlation. In addition, the influence of metal cations on the third-strand binding in Purine-Purine-Pyrimidine (Pu.PuPy) reverse-Hoogsteen triplets has been studied. The ab initio calculations were compared with those from recently introduced force fields (AMBER4.1, CHARMM23, and CFF95). The three-body term in neutral trimers is mostly negligible, and the use of empirical potentials is justified. The only exception is the neutral G.GC Hoogsteen trimer with a three-body term of -4 kcal/mol. Protonated trimers are stabilized by molecular ion-molecular dipole attraction and the interaction within the complex is nonadditive, with the three-body term on the order of -3 kcal/mol. There is a significant induction interaction between the third-strand protonated base and guanine. The calculations indicate an enhancement of the third-strand binding in the G.GC reverse-Hoogsteen trimer due to-metal cation coordination to the N7/O6 position of the third-strand guanine. Interactions between metal cations and complexes of DNA bases are in general highly non-additive; the three-body term is above-10 kcal/mol in a complex of a divalent cation (Ca2+) with the GG reverse-Hoogsteen pair. The pairwise additive empirical potentials qualitatively underestimate the binding energy between cation and base.

The interactions of square platinum(II) complexes with guanine and adenine: a quantum-chemical ab initio study of metalated tautomeric forms

Abstract The influence of binding of square planar platinum complexes on tautomeric equilibria of the DNA bases guanine and adenine was investigated using the density functional B3LYP method. Neutral trans-dichloro(amine)-, +1 charged chloro(diamine)-, and +2 charged triamine-platinum(II) species were chosen for coordination to bases. Only the N7 interaction site of the bases was considered. The calculations demonstrate that the neutral platinum adduct does not change the tautomeric equilibria of the bases. Furthermore, N7 binding of the neutral Pt adduct moderately reduces the probability of protonation of the N1 position of adenine. Larger effects can be observed for +1 and mainly +2 adducts, but these can be rationalized by electrostatic effects. Since the electrostatic effects are expected to be efficiently compensated for by a charged backbone of DNA and counterions in a polar solvent, no dramatic increase in mispair formation is predicted for Pt(II) adducts, which is in agreement with experiment. The interaction energies between Pt adducts and the nucleobases were also evaluated. These interaction energies range from ca. 210 kJ/mol for neutral adducts, interacting with both bases and their tautomers, up to 500 kJ/mol for the +2 charged adducts, interacting with the keto-guanine tautomer and the anti-imino-adenine tautomer. The surprisingly large interaction energy for the latter structure is due to the strong H-bond between the NH3 ligand group of the metal adduct and the N6 nitrogen atom of the base.

The Influence of the Thymine C5 Methyl Group on Spontaneous Base Pair Breathing in DNA

Sequences of four or more AT base pairs without a 5′-TA-3′ step, so-called A-tracts, influence the global properties of DNA by causing curvature of the helix axis if phased with the helical repeat and also influence nucleosome packaging. Hence it is interesting to understand this phenomenon on the molecular level, and numerous studies have been devoted to investigations of dynamical and structural features of A-tract DNA. It was early observed that anomalously slow base pair-opening kinetics were a striking physical property unique to DNA A-tracts (Leroy, J. L., Charretier, E., Kochoyan, M., and Gueron, M. (1988) Biochemistry 27, 8894–8898). Furthermore, a strong correlation between DNA curvature and anomalously slow base pair-opening dynamics was found. In the present work it is shown, using imino proton exchange measurements by NMR spectroscopy that the main contribution to the dampening of the base pair-opening fluctuations in A-tracts comes from the C5 methylation of the thymine base. Because the methyl group has been shown to have a very limited effect on the DNA curvature as well as the structure of the DNA helix, the thymine C5 methyl group stabilizes the helix directly. Empirical potential energy calculations show that methylation of the tract improves the stacking energy of a base pair with its neighbors in the tract by 3–4 kcal/mol.

How to understand quantum chemical computations on DNA and RNA systems? A practical guide for non-specialists

In this review primarily written for non-experts we explain basic methodological aspects and interpretation of modern quantum chemical (QM) computations applied to nucleic acids. We introduce current reference QM computations on small model systems consisting of dozens of atoms. Then we comment on recent advance of fast and accurate dispersion-corrected density functional theory methods, which will allow computations of small but complete nucleic acids building blocks in the near future. The qualitative difference between QM and molecular mechanics (MM, force field) computations is discussed. We also explain relation of QM and molecular simulation computations to experiments.