Monte Carlo study of three-dimensional organization of water molecules around DNA fragments

Interactions with water molecules are important for the stabilization of three-dimensional structures of nucleic acids and for their functioning. The first hydration shells of macromolecules can be considered as structural parts of nucleic acid. We performed a Monte Carlo study of systems containing a nucleic acid base or base pair with water molecules using improved potential functions. These potential functions enable experimental data on both single base–single water interaction energies and enthalpies of base hydration to be reproduced. Hydration shell structures of base pairs are dependent on the pair geometry. Structural elements of hydration shells can contribute to the pair stability and hence to the probability of mispair formation during nucleic acid biosynthesis. The distribution of water molecules around bases and base pairs is essentially nonhomogeneous.From the Proceedings of the 28th Congreso de Químicos Teóricos de Expresión Latina (QUITEL 2002).     

1H NMR Analysis of Heteroassociation of Caffeine with Mitoxanthrone in Aqueous Solution

Heteroassociation of caffeine (CAF) with the antibiotic mitoxanthrone (novatrone, NOV) in aqueous solution was studied by one-dimensional (1D) and two-dimensional (2D) ¹H NMR spectroscopy (500 MHz). The concentration and temperature dependences of the proton chemical shifts of the molecules in aqueous solution have been measured. The equilibrium constants of heteroassociation between CAF and NOV and the limiting proton chemical shifts of the aromatic ligands of the associates have been determined. The most plausible structure of the 1:1 CAF–NOV heterocomplex in aqueous solution was inferred from the calculated values of the induced proton chemical shifts and quantum-mechanical screening curves for CAF and NOV. The thermodynamic parameters of the formation of the CAF–NOV heterocomplex have been calculated. The relatively high heteroassociation constant (K = 256 ± 31 M^–1, T = 318 K), the positive value of entropy for heteroassociation [ S = 15.3 ± 4.0 J/(moleK)], and the structural features of the chromophore of the novatrone molecule indicate that hydrophobic interactions play a significant role in stabilization of the CAF–NOV heterocomplex.     

Analysis of Proton NMR in Hydrogen Bonds in Terms of Lone‐Pair and Bond Orbital Contributions

NMR spectroscopic parameters of the proton involved in hydrogen bonding are studied theoretically. The set of molecules includes systems with internal resonance‐assisted hydrogen bonds, internal hydrogen bonds but no resonance stabilization, the acetic acid dimer (AAD), a DNA base pair, and the hydrogen succinate anion (HSA). Ethanol and guanine represent reference molecules without hydrogen bonding. The calculations are based on zero‐point vibrationally averaged molecular structures in order to include anharmonicity effects in the NMR parameters. An analysis of the calculated NMR shielding and J‐coupling is performed in terms of “chemist’s orbitals”, that is, localized molecular orbitals (LMOs) representing lone‐pairs, atomic cores, and bonds. The LMO analysis associates some of the strong de‐shielding of the protons in resonance‐assisted hydrogen bonds with delocalization involving the π‐backbone. Resonance is also shown to be an important factor causing de‐shielding of the OH protons for AAD and HSA, but not for the DNA base pair. Nitromalonamide (NMA) and HSA have particularly strong hydrogen bonds exhibiting signs of covalency in the associated J‐couplings. The analysis results show how NMR spectroscopic parameters that are characteristic for hydrogen bonded protons are influenced by the geometry and degree of covalency of the hydrogen bond as well as intra‐ and intermolecular resonance.     

DNA sequencing with titanium nitride electrodes

We construct a hydrogen‐bond based metal–molecule–metal junction, which contains two identical “reader” molecules, one single DNA base as a bridged molecule, and two titanium nitride electrodes. Hydrogen bonds are formed between “reader” molecules and DNA base, whereas titanium–sulfur bonds are formed between “reader” molecules and titanium nitride electrodes. We perform electronic structure calculations for both the bare bridged molecule and the full metal–molecule–metal system. The projected density of states shows that when the molecule is connected to the titanium nitride electrode, the energy levels of the bridged molecule are shifted, with an indirect effect on the hydrogen bonds. This is similar to the case for a gold electrode but with a more pronounced effect. We also calculate the current–voltage characteristics for the molecular junctions containing each DNA base. Results show that titanium nitride as an electrode can generate distinct conductance for each DNA base, providing an alternative electrode for DNA sequencing. © 2013 Wiley Periodicals, Inc.     

Quantum-chemical investigation of the complex of Mg-porphin with tetracyanoquinodimethane

The potential hypersurface for the interaction of the molecules of Mg-porphin (P) and tetracyanoquinodimethane (TCQ) was investigated by the CNDO/2 method. The calculated energy minimum amounts to –8.95 eV and corresponds to a distance of 2.1 Å between the planes of the molecules with some displacement in relation to the central mutual arrangement. The results are regarded as tentative in view of the fact that the CNDO/2 method exaggerates the interaction. The electronic spectra of the P·TCQ complex are calculated by the CNDO/S-CI method for a series of arrangements of P and TCQ. Satisfactory agreement with experiment is obtained with a distance of about 3 Å between the planes of the molecules. It was shown that there are two transitions with charge transfer in the near IR region of the spectrum and also several transitions of the same type in the visible and near UV regions.Translated from Teoreticheskaya i Éksperimental'naya Khimiya, Vol. 26, No. 4, pp. 431–437, July–August, 1990.     

Solution structure of a DNA duplex containing a guanine-difluorotoluene pair: a wobble pair without hydrogen bonding?

The incorporation of synthetic nucleoside analogues into DNA duplexes provides a unique opportunity to probe both structure and function of nucleic acids. We used 1H and 19F NMR and molecular dynamics calculations to determine the solution structures of two similar DNA decamer duplexes, one containing a central G-T mismatched or "wobble" base pair, and one in which the thymine in this base pair is replaced by difluorotoluene (a thymine isostere) creating a G-F pair. Here, we show that the non-hydrogen-bonding G-F pair stacks relatively well into the helix and that the distortions caused by each non-Watson-Crick G-T or G-F base pair are quite localized to a three base pair site around the mismatch. A detailed structural analysis reveals that the absence of hydrogen bonding introduces more dynamic motion into the G-F pair relative to G-T and permits the G-F pair to exhibit stacking and conformational features characteristic of both a Watson-Crick base pair (on the guanine containing strand) and a wobble base pair (on the strand containing the difluorotoluene). We used these results to posit a rationale for recognition and repair of mismatch sites in DNA.     

Rationalization of the optical rotatory power of chiral molecules into atomic terms: a study of N<Subscript>2</Subscript>H<Subscript>4</Subscript>

We applied a strategy to assign the individual contributions that atoms make to the optical rotation angle and, more generally, to the molecular chirality. The method resolves the optical rotatory power tensor into atomic contributions employing the formalism of the acceleration gauge for the electric dipole and the torque formalism for the magnetic dipolar moment. The gross atomic isotropic contributions have been evaluated for nitrogen and hydrogen in hydrazine, employing Gaussian basis sets of very good quality, in order to achieve the Hartree–Fock limit.From the Proceedings of the 28th Congreso de Químicos Teóricos de Expresión Latina (QUITEL 2002)     

Deuterium isotope effects in A:T and A:U base pairs: a computational NMR study

Recent measurements of trans-hydrogen bond deuterium isotope effects (DIEs) on 13C chemical shifts in nucleic acids (Vakonakis, I.; LiWang, A. C. J. Biomol. NMR 2004, 29, 65; J. Am. Chem. Soc. 2004, 126, 5688) have led to intriguing results: (i) the DIEs of A:T pairs in DNA are about 5 ppb smaller than those of A:U in RNA and (ii) A:T DIEs vary by as much as 13 ppb among the oligonucleotides. The first observation suggests that inter-base H-bonds in RNA may be stronger than those in DNA, while the second indicates that the conformation of the base pair modulates the transmission of the isotope effect across the hydrogen bond. In an effort at providing a rationale--so far unknown--for the observed DIEs in nucleic acids, density functional theory and hybrid Car-Parrinello/molecular mechanical calculations of DIEs on nucleosides and nucleotides in the gas phase and in aqueous solution have been performed. The calculations suggest that (i) the DIE in an isolated A:T base pair differs from that in an A:U base pair because of the changes in the magnetic properties caused by the replacement of a methyl group on passing from U to T, (ii) the DIEs depend crucially on the conformation of the base pairs, and (iii) the DIEs are strongly affected by magnetic and electrostatic interactions with the surrounding environment.     

Diacetylene's weak bonding to acetylene clusters

An interaction potential previously developed for the acetylene–polyyne dimer was used to explore the interaction potential surfaces for clusters containing a diacetylene molecule and two or more acetylene molecules. Ab initio calculations were performed on the smallest clusters in order to assess the energetic and structural features predicted by the model potential. The preferred arrangements of the monomers in the clusters maximize the favorable quadrupole–quadrupole interactions between the monomers.     

Hydration and stability of nucleic acid bases and base pairs

Empirical, quantum chemical calculations and molecular dynamics simulations of the role of a solvent on tautomerism of nucleic acid bases and structure and properties of nucleic acid base pairs are summarized. Attention was paid to microhydrated (by one and two water molecules) complexes, for which structures found by scanning of empirical potential surfaces were recalculated at a correlated ab initio level. Additionally, isolated as well as mono- and dihydrated H-bonded, T-shaped and stacked structures of all possible nucleic acid base pairs were studied at the same theoretical levels. We demonstrate the strong influence of a solvent on the tautomeric equilibrium between the tautomers of bases and on the spatial arrangement of the bases in a base pair. The results provide clear evidence that the prevalence of either the stacked or hydrogen-bonded structures of the base pairs in the solvent is not determined only by its bulk properties, but rather by specific hydrophilic interactions of the base pair with a small number of solvent molecules.     

A quantum chemical study of red-shift and blue-shift hydrogen bonds in bimolecular and trimolecular methylhydrazine-hydrate complexes

This study presents a theoretical discussion of the geometry and molecular parameters of the methylhydrazine-hydrate complex. Using B3LYP/6-311++G(d,p) calculations, two geometries for the methylhydrazine-hydrate complex were analyzed by considering the interaction between water in: (i) a lone nitrogen pair assisted by a methyl (I); and (ii) the nitrogen of the NH₂ group (II). These geometries were examined by examining the formation of (N···H) hydrogen bonds, which were characterized using ChelpG charge transfer amounts, as well as by means of topological parameters derived from Quantum Theory of Atoms in Molecules (QTAIM) calculations. In a qualitative evaluation, both complexes (a) and (b) were compared with the corresponding trimolecular system (c) formed by methylhydrazine and two water molecules. A conclusion was then obtained by means of vibrational analysis, in which, in addition to δυ(H–O) red-shifts in water molecules, the stretch frequency of the H–C bond of methyl group shifted upwards, indicating the formation of a blue-shifting hydrogen bond in the methylhydrazine-bihydrate complex.     

Folding of a stable DNA motif involves a highly cooperative network of interactions

Hairpins are structural elements that play important roles in the folding and function of RNA and DNA. The extent of cooperativity in folding is an important aspect of the RNA folding problem. We reasoned that an investigation into the origin of cooperativity might be best carried out on a stable nucleic acid system with a limited number of interactions, such as a stable DNA hairpin loop. The stable d(cGNAg) hairpin loop motif (closing base pair in lower case; loop in upper case; N = A, C, G, or T) is stabilized through only three interactions: two loop-loop hydrogen bonds in a sheared GA base pair and a loop-closing base pair interaction. Herein, we investigate this network of interactions and test whether the loop-loop and loop-closing base pair interactions communicate. Thermodynamic measurements of nucleotide analogue substituted oligonucleotides were used to probe the additivity of the interactions. On the basis of double mutant cycles, all interactions were found to be nonadditive and interdependent, suggesting that loop-loop and loop-closing base pair interactions form in a highly cooperative manner. When double mutant cycles were repeated in the absence of the other interaction, nonadditivity was significantly reduced suggesting that coupling is indirect and requires all three interactions in order to be optimal. A cooperative network of interactions helps explain the structural and energetic bases of stability in certain DNA hairpins and paves the way for similar studies in more complex nucleic acid systems.     

Use of molecular analogs for the bases in DNA: Stability of molecular pairs in gas phase and aqueous media and possible role of hydrogen bonding

In a recent experimental study, it was reported that replacement of thymine in the adenine–thymine base pair of DNA by its molecular analogs which cannot form proper hydrogen bonds with adenine (A) does not cause disruption of DNA structure and synthesis. AM1 and ab initio molecular orbital calculations and electric field mapping were carried out in order to examine the possibility of pairing of A with each one of two analogs of thymine in the gas phase. Self-consistent reaction field calculations were also carried out on the individual molecules and their pairs using the polarized continuum model in order to examine their stability in aqueous media. Our results are broadly in agreement with the conclusions drawn in the above-mentioned experimental work. © 1998 John Wiley & Sons, Inc. Int J Quant Chem 68: 351–355, 1998     

Conformational analysis of double-helical polynucleotides

The intramolecular interaction energy of the regular double-helical polynucleotide as a function of variables that determine the mutual position of base pairs and sugar pucker was calculated using atom–atom potentials. The calculations showed the existence of two valley-like regions with minimal values on the energetic surface. One of them corresponds to the A family of nucleic acids, the other to the B family. The points that correspond to the models constructed by means of x-ray data are placed in a conformational space near the lines that describe the position of the bottom of the valleys.     

Structure of adducts of the intermolecular interaction of dimethylpyrazole and diphenylformamidine with hydrogen halides in the solution

The structure of adducts forming in the solution due to the interaction of bifunctional azo compounds (dimethylpyrazole (DMP) and diphenylformamidine (DPFA)) with hydrogen halides (HF, HCl, and HBr) is found from the data of the IR absorption spectra and quantum chemical calculations. It is shown that in the interaction with HCl or HBr proton donors, proton transfer via the hydrogen bond to the basic N atom of the azo compound occurs with the formation of an NH⁺…Hal⁻ ionic pair. Strong evidences of proton transfer and the anion-cation pair formation are not found for the DMP-_F structure, and complexes with the molecular N…HF hydrogen bond are the dominant structures. Geometric parameters of the formed structures are calculated. The formation of trimers, containing two molecules of the azo compound and one HHal molecule, with an increase in the nitrogenous base concentration is experimentally proved, and the trimer structure is determined.     

The Effect of Deoxyfluorination on Intermolecular Interactions in the Crystal Structures of 1,6-Anhydro-2,3-epimino-hexopyranoses

The effect of substitution on intermolecular interactions was investigated in a series of 1,6-anhydro-2,3-epimino-hexopyranoses. The study focused on the qualitative evaluation of intermolecular interactions using DFT calculations and the comparison of molecular arrangements in the crystal lattice. Altogether, ten crystal structures were compared, including two structures of C4-deoxygenated, four C4-deoxyfluorinated and four parent epimino pyranoses. It was found that the substitution of the original hydroxy group by hydrogen or fluorine leads to a weakening of the intermolecular interaction by approximately 4 kcal/mol. The strength of the intermolecular interactions was found to be in the following descending order: hydrogen bonding of hydroxy groups, hydrogen bonding of the amino group, interactions with fluorine and weak electrostatic interactions. The intermolecular interactions that involved fluorine atom were rather weak; however, they were often supported by other weak interactions. The fluorine atom was not able to substitute the role of the hydroxy group in molecular packing and the fluorine atoms interacted only weakly with the hydrogen atoms located at electropositive regions of the carbohydrate molecules. However, the fluorine interaction was not restricted to a single molecule but was spread over at least three other molecules. This feature is a base for similar molecule arrangements in the structures of related compounds, as we found for the C4-F_ax and C4-F_eq epimines presented here.     

Self-consistent-field – Hartree–Fock method with finite nuclear mass corrections

We have upgraded a Self-consistent-field – Hartree–Fock routine to include a finite nuclear mass correction for molecules developed in our laboratory. The new routine can handle isotopomers without calculating any nuclear kinetic energy matrix element. Tests on H₂, LiH, HF, F₂, and H₂O isotopomers indicate the equivalence of our correction to the standard diagonal adiabatic correction. A further original application to C₂H₆ illustrates the usefulness of the method for polyatomic molecules. The resulting molecular orbitals carry the nuclear mass signature, exemplified with Koopmans ionization potentials.From the Proceedings of the 28th Congreso de Químicos Teóricos de Expresión Latina (QUITEL 2002)     

Spatial arrangement of alpha-cyclodextrins in a rotaxane. Insights from free-energy calculations

The rotaxane formed by alpha-cyclodextrins (alpha-CDs) threaded onto a poly(ethylene glycol) (PEG) chain was investigated in the gas phase and in an aqueous solution by means of molecular dynamics simulations. The free-energy difference between the three possible spatial arrangements of consecutive alpha-CD--viz.. head-to-head (HH), head-to-tail (HT), and tail-to-tail, was determined using free-energy perturbation calculations. These simulations reveal that the interaction of alpha-CD with the PEG chain is very similar in the two surroundings, whereas the mutual interaction of the macrocycles is stronger in the gas phase than in the aqueous solution. Moreover, difference in the overall interaction appears to stem primarily from changes in the electrostatic contribution. Analysis of intermolecular hydrogen bonds indicates that hydrogen bonds created between alpha-CD and water molecules weaken the hydrogen-bonding interaction of adjacent alpha-CDs. Comparison of the free-energy differences characteristic of the three possible spatial arrangements of contiguous alpha-CDs reveals that the HH motif of the rotaxane is the most stable in the gas phase due to the hydrogen-bond formation between the secondary hydroxyl groups of the two alpha-CDs, and the slight preference for the HT motif in aqueous solution, which can be related to the directionality of the dipole moment borne by the macrocycles in these two motifs.     

Role of Complex Formation in Mass Transport during Nickel Electrodeposition from Low-Concentration Formate–Chloride Electrolytes

Nickel electrodeposition from 0.2 M formate–chloride solutions is studied. Depending on electrolyte pH₀, the highest current density of the electrodeposition of compact nickel deposits varies from 3 (pH₀3.5) to 40 A dm^–2(pH₀2.0). With the current efficiency for nickel taken into account, this corresponds to nickel deposition rates of 3 to 25 A dm^–2. One of the reasons for the high permissible current densities is good buffer properties of the electrolyte. Computer calculations show that the considerable acceleration of the nickel electrodeposition is due to mass transport accelerated by the formation of complex [NiL]⁺cations. The complex formation also affects the intensity of interaction between nickel and hydrogen ions transported to the cathode. The current by nickel increases due to the participation of formic acid molecules in the hydrogen evolution.     

Some Structural and Thermodynamic Aspects of Solvation of Single Ions. 2. Salt Effects in Aqueous Solutions of 1–1 Electrolytes

The ionic coefficients of the pair interionic interaction in aqueous solutions of 1–1 electrolytes at 298 K were determined from the real activity coefficients of single-charged single ions using the McMillan–Mayer formalism. Analysis of the results of calculations revealed that salt effects are stronger in the case of cations. The weakening of cation hydration (increased negative hydration) and the strengthening of anion hydration (increased positive hydration) enhance the mutual salting of cations and anions. It is shown that the structural effects of hydration produce a strong effect on the interionic interaction in solutions.