How strong can the bend be on a DNA helix from cisplatin? DFT and MP2 quantum chemical calculations of cisplatin-bridged DNA purine bases

The B3LYP/6-31G(d) level of theory was used for the optimization of [Pt(NH(3))(4)](2+), [Pt(NH(3))(3)(H(2)O)](2+), cis-[Pt(NH(3))(2)(H(2)O)(2)](2+), and related platinum complexes. In addition, water or ammonium ligands were replaced by DNA purine bases so that finally cis-diammineplatinum with two bases (Pt-bridged complexes) is obtained. Single point calculations using the MP2/6-31+G(d) method were performed on the obtained reference geometries and were utilized for estimating bond dissociation energies (BDEs) and stabilization energies, and for electron density analyses. After reoptimization, IR spectra were determined from HF second derivatives. It was found that replacement of both water and ammonium by the DNA base is an exothermic process (20-50 kcal/mol depending on the ligands present in the complex). Asymmetric structures with one interbase H-bond were obtained for cis-diammine[bond](N(7),N(7)'-diadenine)[bond]platinum and mixed cis-diammine[bond](N(7)-adenine)[bond](N(7)-guanine)[bond]platinum complexes. In the case of the diguanine Pt-bridge, a symmetrical complex with two ammonium...O(6) H-bonds was found. The higher stabilization energy of the di-guanine complex is linked to a larger component of the Coulombic interaction. However, the BDE of Pt[bond]N(7)(G) is smaller in this complex than the BDE of Pt[bond]N(7)(G) from the mixed Pt[bond]AG complex. Also, steric repulsion of the ligands is about 10 kcal/mol smaller for the asymmetrical Pt[bond]AA and Pt[bond]AG bridges. The influence of the trans effect on DBE can be clearly seen. Adenine exhibits the largest trans effect, followed by guanine, ammonium, and water. The strength of the H-bond can be determined from the IR spectra. The strongest H-bond is the interbase H-bridge between adenine and guanine in the mixed Pt[bond]AG complex; otherwise, the H-bonds of adenine complexes are weaker than in guanine complexes. BDE can be traced in the guanine-containing complexes. The nature of the covalent bonding is analyzed in terms of partial charges and MO. A general explanation of the lower affinity of transition metals to oxygen than nitrogen can be partially seen in the less favorable geometrical orientation of lone electron pairs of oxygen.     

Hydrogen-bonding interactions in peptide nucleic acid and deoxyribonucleic acid: a comparative study

Peptide nucleic acid (PNA) is a synthetic analogue of deoxyribonucleic acid (DNA) capable of tightly binding to itself and DNA with high specificity. Using hybrid density functional methods, hydrogen-bond (H-bond) strengths have been evaluated for isolated Watson-Crick base pairs, PNA base pairs, and charged as well as neutral DNA base pairs. Heterogeneous base pairs of PNA with charged and neutral DNA have also been investigated. The competing effects of short-range H-bonding and long-range Coulombic repulsions in charged DNA base pairs have been analyzed. Polarizable continuum models have been employed to evaluate solvation effects on the binding energies.     

Enantioselective recognition of 1,2-amino alcohols by reversible formation of imines with resonance-assisted hydrogen bonds

A chiral aldehyde with three H-bond donating groups (2) has been synthesized. This aldehyde binds a variety of chiral 1,2-amino alcohols in benzene with the same sense of stereoselectivity. Computational and experimental data indicate that one imine bond, one resonance-assisted H-bond to the imine nitrogen, and two H-bonds to the alcoholic oxygen all play an important role in the stereoselective recognition. [structure: see text]     

Characterizing the strength of individual hydrogen bonds in DNA base pairs

The energies of individual hydrogen bonds (H-bonds) in A-T and G-C Watson-Crick base pairs were calculated according to the natural bond orbital (NBO) analysis of intermolecular interactions. The extent to which individual H-bonds are helpful in holding the two base pairs together was previously investigated quantitatively by a few different approaches, and the results of the present and previous estimations were compared. The method was validated by the determination of the H-bond strength changes in A-T and G-C pairs upon the substitution of the monomer (base) by two cationic substituents; the systems for which the changes were previously anticipated based on the modifications of the H-bonds' distances.     

Marked variations of dissociation energy and H-bond character of the guanine-cytosine base pair induced by one-electron oxidation and Li+ cation coupling

The variation of dissociation energy and H-bond character of the G-C cation and the Li-GC cation have been investigated by employing density functional theory (B3LYP) with the 6-31+G* basis set. The one-electron oxidation and the coupling of Li(+) to the guanine-cytosine base pair can strengthen the interaction between guanine and cytosine. The interaction of the cation Li(+) with guanine is attractive and is attributed to the polarization of the H-bonds between G-C that enhances G-C interaction. The cooperativity of the three H-bonds in the GC and Li-GC cations is different from that in the neutral GC base pair. The proton-transfer process between N(1) of the guanine and N(3) of the cytosine can occur in the GC cation and the Li-GC cation. The geometries of the transition state are out of plane, especially for the transition state of the Li-GC cation. The analysis of the activation energy for the proton-transfer process shows that the GC(+) before and after proton transfer can exist simultaneously in the gas phase, but for the Li-GC(+) system, the Li-GC(+) without proton transfer is the dominating species in the gas phase.     

Hydrogen bonding in Schiff bases--NMR, structural and experimental charge density studies

A series of sixteen Schiff bases (derivatives of salicylaldehydes and aryl amines) was studied to reveal the influence of substituents and the length of the linker on the properties of the H-bonding formed. In theory, two groups of compounds, derivatives of 2-(2-hydroxybenzylidenoamine)phenol) and 2-hydroxy-N-(2-hydroxybenzylideno)benzylamine, can form different types of H-bonds using one or two hydroxyl groups present in the molecules. Two other groups of compounds, derivatives of 4-(2-hydroxybenzylidenoamine)phenol and N-(2-hydroxybenzyideno)benzylamine, can form only one type of H-bond. It was confirmed by (15)N and (13)C NMR experiments, that in all cases only traditional, H-bonded six-membered chelate rings were formed. The positions of the hydrogen atom in the rings depend on the substituent and phase. Generally, the OH H-bond form dominates in solution, with exception of the nitro derivatives, where the NH tautomer is present. In the solid state the tautomeric equilibrium is strongly shifted to the NH form. Only for the 5-Br derivative of one compound was the reverse relationship found. According to the results of experimental charge density investigations, two intramolecular H-bonds in the 5-methoxy derivative of 2-hydroxy-N-(2'-hydroxybenzylideno)benzylamine) differ significantly in terms of charge density properties. The intra- and intermolecular H-bonds formed by the deprotonated oxygen atom from 2-OH group are strong, with significant charge density concentration at the bond critical point and a straight, well-defined bond path, whereas the second intramolecular H-bond formed by the oxygen atom from the 2'-OH group is quite weak, with ca. five times smaller charge density concentration than in the previous case and a bent bond path. In terms of energy densities, the latter H-bond appears to be a non-bonding interaction, with total energy density being slightly positive. In terms of source contributions to the density at the H-bond critical point from the atoms involved, the intermolecular, linear H-bond is very strong and charge-assisted in the source function classification, the N(1)-H(1N)···O(1) H-bond is medium-strength, while the third H-bond is extremely weak.     

Molecular basis of the recognition process: hydrogen-bonding patterns in the guanine primary recognition site of ribonuclease T1

Investigation of the intrinsic H-bonding pattern of the guanine complex with a sizable segment (from Asn43 to Glu46) of the primary recognition site (PRS) in RNase T1 at the B3LYP/6-311G(d,p) level of theory enables the electronic density characteristics of the H-bonding patterns of the guanine-PRS complexes to be identified. The perfect H-bonding pattern in the guanine recognition site is achieved through the guanine complex interactions with the large segment of the PRS. Two significant short H-bonds, O epsilon 1...HN1 and O epsilon 2...HN2, have been identified. The similar short H-bond distances found in the anionic GC- base pair and in this study suggest that the short hydrogen-bond distances may be characteristic of the multiple H-bonded anionic nucleobases. The H-bonding energy distribution, the geometric analysis of the H-bonding pattern, and the electron structure characteristics of the H-bonds in the guanine PRS of RNase T1 all suggest that the O epsilon 1...HN1 and O epsilon 2...HN2 side-chain H-bonds dominate the binding at the guanine recognition site of RNase T1. Also, the geometry evidence, the electron structure characteristics, and the properties of the bond critical points of the H-bonds reveal that the side-chain H-bonding and the main-chain H-bonding are mutually intensifying. Thus the positive cooperativity between Asn43 to Tyr45 and Glu46 is proposed.     

At nonzero temperatures, stacked structures of methylated nucleic acid base pairs and microhydrated nonmethylated nucleic acid base pairs are favored over planar hydrogen-bonded structures: a molecular dynamics simulations study

The dynamic structure of all ten possible nucleic acid (NA) base pairs and methylated NA base pairs hydrated by a small number of water molecules (from 1 to 16) was determined by using molecular dynamics simulations in the NVE microcanonical and NVT canonical ensembles with the Cornell force field (W. D. Cornell, P. Cieplak, C. I. Bayly, I. R. Gould, K. M. Merz, D. M. Ferguson, D. C. Spellmeyer, T. Fox, J. E. Caldwell, P. Kollman, J. Am. Chem. Soc. 1995, 117, 5179). The presence of one water molecule does not affect the structure of any hydrogen-bonded (H-bonded) nonmethylated base pair. An equal population of H-bonded and stacked structures of adenine...adenine, adenine...guanine and adenine... thymine pairs is reached if as few as two water molecules are present, while obtaining equal populations of these structures in the case of adenine...cytosine, cytosine...thymine, guanine... guanine and guanine...thymine required the presence of four water molecules, and in the case of guanine...cytosine, six. A comparable population of planar, H-bonded and stacked structures for cytosine...cytosine and thymine... thymine base pairs was only obtained if at least eight water molecules hydrated a pair. Methylation of bases changed the situation dramatically and stacked structures were favoured over H-bonded ones even in the absence of water molecules in most cases. Only in the case of methyl cytosine...methyl cytosine, methyl guanine...methyl guanine and methyl guanine...methyl cytosine pairs were two, two or six water molecules, respectively, needed in order to obtain a comparable population of planar, H-bonded and stacked structures. We believe that these results give clear evidence that the preferred stacked structure of NA base pairs in the microhydrated environment, and also apparently in a regular solvent, is due to the hydrophilic interaction of a small number of water molecules. In the case of methylated bases, it is also due to the fact that the hydrogen atoms most suitable for the formation of H-bonds have been replaced by a methyl group. A preferred stacked structure is, thus, not due to a hydrophobic interaction between a large bulk of water molecules and the base pair, as believed.     

与蛋白质调控DNA空穴迁移相关的具有负离解能特征的亚稳态氢键

利用密度泛函理论方法研究了作为空穴迁移载体的蛋白质复合的DNA三聚体(Protonated arginine…guanine…cytosine, ArgH⁺-GC)的氢键性质. 结果表明, 空穴迁移通过该载体单元时此类氢键表现为亚稳态, 且具有明显的负离解能. 正常情况下ArgH⁺基团在大小沟均能与GC碱对形成氢键, 且具有正的离解能. 然而, 当空穴转移至此将削弱氢键至亚稳态, 使之具有一定的离解势垒和负的离解能. 这种势垒抑制的负离解能现象意味着由于空穴俘获导致此三聚体结构单元在它的ArgH⁺…N7/O6键区储存了一定的能量(约108.78 kJ/mol). 该氢键离解通道受控于此键区两个相关组分之间的静电排斥和氢键吸引之间的平衡以及这两个相反作用随氢键距离不同的衰减速率. 基于电子密度分布的拓扑性质以及键临界点的Laplacian数值分析澄清了此类特殊的能量现象主要源自通过高能氢键(ArgH⁺…N7/O6)连接的授受体间的静电排斥. 进一步空穴俘获诱导的G→C质子转移可扩展负离解能区至ArgH⁺…N7/O6和Watson-Crick(WC) 氢键区. 另外, ArgH⁺ 结合到GC的大小沟增加其电离势, 因此削弱其空穴传导能力, 削弱程度取决于ArgH⁺与GC的距离. 推而广之, 在protonated lysine-GC和protonated histidine-GC体系也可观察到类似的现象. 显然, 此类性质可调的亚稳态氢键可调控DNA空穴迁移机理. 此工作为理解蛋白质调控的DNA空穴迁移机理提供了重要的能量学信息.     

Intramolecular hydrogen bond energy and cooperative interactions in α-, β-, and γ-cyclodextrin conformers

Accurate estimation of individual intramolecular hydrogen bond (H-bond) energies is an intricate task for multiply H-bonded systems. In such cases, the hydrogen bond strengths could be highly influenced by the cooperative interactions, for example, those between hydroxyl groups in sugars. In this work, we use the recently proposed molecular tailoring approach-based quantification (Deshmukh, Gadre, and Bartolotti, J Phys Chem A 2006, 110, 12519) to the extended systems of cyclodextrins (CDs). Further, the structure and stability of different conformers of α-, β-, and γ-CDs are explained based on the energetics and cooperative contribution to the strength of these H-bonds. The estimated O-H···O H-bond energies in the various CD conformers are found to vary widely from 1.1 to 8.3 kcal mol(-1). The calculated energy contributions to cooperativity toward the H-bond strengths fall in the range of 0.25-2.75 kcal mol(-1).     

Study of H-bond characteristics in sub- and supercritical methanol

Classical molecular dynamics simulations of various methanol phase lines near the saturation curve and the critical point have been performed to study the changes in H-bonded clusters structure at transition of methanol to supercritical state. Analysis of H-bonds statistics with combined distance-energy H-bond criterion showed that the correlations between topological characteristics of H-bonds and the mole fraction of H-bonded molecules have unique functional representation despite the phase path applied. In the present study, an attempt has been also made to evaluate the degree of hydrogen bonding by combining the DFT computations on classical MD configurations with the natural bond orbital analysis of the waves functions obtained.     

Do H-bond features of silica surfaces affect the H2O and NH3 adsorption? Insights from periodic B3LYP calculations

The adsorption of a single H(2)O and NH(3) molecule on different fully hydroxylated α-quartz, cristobalite, and tridymite surfaces has been studied at the B3LYP level of theory, within a periodic approach using basis sets of polarized triple-ζ quality and accounting for basis set superposition error (BSSE). Fully hydroxylated crystalline silica exhibits SiOH as terminal groups whose distribution and H-bond features depend on both the considered silica polymorph and the crystallographic plane, which gives rise to isolated, H-bond interacting SiOH pairs or infinitely connected H-bond chains. A key point of the present study is to understand how the H-bond features of a dry crystalline silica surface influence its adsorption properties. Results reveal that the silica-adsorbate (H(2)O and NH(3)) interaction energy anticorrelates with the density of SiOH groups at the surface. This counterintuitive observation arises from the fact that pre-existing H-bonds of the dry surface need to be broken to establish new H-bonds between the surface and the adsorbate, which manifests in a sizable energy cost due to surface deformation. A simple method is also proposed to estimate the strength of the pre-existing H-bonds at the dry surfaces, which is shown to anticorrelate with the adsorbate interaction energy, in agreement with the above trends.     

Protonic Quantum Correlations in the H-Bond Dynamics of Nucleic Acids. Part 1. Conformational comparison of G-C with Benner's κ-π

A new base pair (called κ-π) of Watson-Crick type, with an H-bond pattern different from that in A-T and G-C base pairs, has been recently synthesized by Benner and coworkers and shown to be stable and incorporable into duplex DNA and RNA by polymerases. This new base pair, which contains three H-bonds, is compared with G-C, in the framework of modern dynamical theory of quantum nonlocality and quantum correlations (also called Einstein-Podolsky-Rosen correlations). Connection with the traditional treatment of proton transfer in DNA base pairs, which uses the adiabatic approximation (thus considering the protons as classical particles), is explicitly made. As a result, the dynamics of the H-bond pattern of G-C is shown to exhibit a specific quantum-mechanical phase stability (or: rigidity, stiffness), which is clearly missing in the case of κ-π. This finding is discussed and illustrated, also in connection with recent quantum chemical calculations of proton transfers in DNA base pairs. Additionally, certain speculations concerning a probable ‘evolutionary advantage’ of G-C with respect to κ-π are shortly considered.     

Direct evaluation of individual hydrogen bond energy in situ in intra- and intermolecular multiple hydrogen bonds system

The results of evaluating the individual hydrogen bond (H-bond) strength are expected to be helpful for the rational design of new strategies for molecular recognition or supramolecular assemblies. Unfortunately, there is few obvious and unambiguous means of evaluating the energy of a single H-bond within a multiple H-bonds system. We present a local analytic model, ABEEMσπ H-bond energy (HBE) model based on ab initio calculations (MP2) as benchmark, to directly and rapidly evaluate the individual HBE in situ in inter- and intramolecular multiple H-bonds system. This model describes the HBE as the sum of electrostatic and van der Waals (vdW) interactions which all depend upon the geometry and environment, and the ambient environment of H-bond in the model is accounted fairly. Thus, it can fairly consider the cooperative effect and secondary effect. The application range of ABEEMσπ HBE model is rather wide. This work has discussed the individual H-bond in DNA base pair and protein peptide dimers. The results indicate that the interactions among donor H atom, acceptor atom as well as those atoms connected to them with 1,2 or 1,3 relationships are all important for evaluating the HBE, although the interaction between the donor H atom and the acceptor atom is large. Furthermore, our model quantitatively indicates the polarization ability of N, O, and S in a new style, and gives the percentage of the polarization effect in HBE, which can not be given by fixed partial charge force field.     

Structure, stability, and dynamics of canonical and noncanonical base pairs: quantum chemical studies

The importance of non-Watson-Crick base pairs in the three-dimensional structure of RNA is now well established. The structure and stability of these noncanonical base pairs are, however, poorly understood. We have attempted to understand structural features of 33 frequently occurring base pairs using density functional theory. These are of three types, namely (i) those stabilized by two or more polar hydrogen bonds between the bases, (ii) those having one polar and another C-H...O/N type interactions, and (iii) those having one H-bond between the bases and another involving one of the sugars linked to the bases. We found that the base pairs having two polar H-bonds are very stable as compared to those having one C-H...O/N interaction. Our quantitatively analysis of structures of these optimized base pairs indicates that they possess a different amount of nonplanarity with large propeller or buckle values as also observed in the crystal structures. We further found that geometry optimization does not modify the hydrogen-bonding pattern, as values of shear and open angle of the base pairs remain conserved. The structures of initial crystal geometry and final optimized geometry of some base pairs having only one polar H-bond and a C-H...O/N interaction, however, are significantly different, indicating the weak nature of the nonpolar interaction. The base pair flexibility, as measured from normal-mode analysis, in terms of the intrinsic standard deviations of the base pair structural parameters are in conformity with those calculated from RNA crystal structures. We also noticed that deformation of a base pair along the stretch direction is impossible for all of the base pairs, and movements of the base pairs along shear and open are also quite restricted. The base pair opening mode through alteration of propeller or buckle is considerably less restricted for most of the base pairs.     

Computational investigation of the role of hydration in nucleic acid structure and function

The results of the Monte Carlo Metropolis simulation of water structure and of the hydration of nucleic acid fragments, complementary base pairs and mispairs, base pair stacks, and duplex fragments have been summarized. Systematic investigations suggest some general conclusions: (1) the hydration shell structure of the major and minor grooves of the duplex depends significantly on DNA conformation (or stack configuration) and nucleotide sequence, while global hydration characteristics (average energy, the number of water–water and water–base H-bonds) are only slightly dependent on these factors, (2) hydration economy takes place in the B–A transition due to an increase of the number of water molecules forming hydrogen bonds with two or more atoms of bases (water bridging), and (3) the hydration of the duplex could contribute to nucleic acid functioning via water-bridged mispair formation and stabilization of specific conformations.     

Characteristics of antiaromatic ring pi multi-hydrogen bonds in (H2O)n-C4H4 (n = 1, 2) complexes

By counterpoise-corrected optimization method, the six antiaromatic ring pi multi-hydrogen bond structures with diversiform shapes for (H2O)n-C4H4 (n = 1,2) have been obtained at the MP2/aug-cc-pVDZ level. At the CCSD(T)/aug-cc-pVDZ level, the interaction energy obtained mainly depends on the numbers of H2O and fold numbers of the pi multi-hydrogen bond. The interaction energy order is -2.342 (1a with pi mono-hydrogen) < -2.777 (1b with pi bi-hydrogen) < -4.683 (2a with pi bi-hydrogen) < -4.734 (2b with pi tri-hydrogen) < -4.782 (2c with pi tri-hydrogen) < -5.009 kcal/mol (2d with pi tetra-hydrogen bond). Strangely, why is the interaction energy of the pi bi-hydrogen bond in 1b close to that of the pi mono-hydrogen bond in 1a (their difference is only 15.7%)? The reason is that a pi-type H-bond (as an accompanying interaction) between two lone pairs of the O-atom and a near pair of H-atoms of C4H4 exists shoulder by shoulder in structures 1a, 2a, 2b, and 2c and contributes to the interaction energy. Another accompanying interaction, a repulsive interaction between the pi H-bond (using the H-atom(s) of H2O) and the near pair of H-atoms of C4H4, is also found. For the structures and interaction energies, the pi-type H-bond produces four effects: bending the strong pi H-bond, attracting the pair of H-atoms of C4H4 so that they deviate from the C4 ring plane, showing the interaction energy contribution, and bringing the larger electron correlation contribution. The repulsive interaction also produces four effects: pushing the pair of H-atoms of C4H4 so that they deviate from its ring plane, elongating the distance of the pi H-bond, promoting the formation of pi-type H-bond, and slightly influencing the interaction energy. In the present paper, one C=C bond with two H2O (over and below the ring plane) forms a pi H-bond link in two ways: a strong-weak pi H-bond link and a strong-strong pi H-bond link. The stability contribution of the former is more favorable than the latter. One H2O forms a pi H-bond with C4H4 in two ways. One strong pi H-bond part (over or below the ring plane) always is accompanied by another H-bond part. The accompanying part is either a weak pi H-bond or pi-type H-bond.     

Nature of one-dimensional short hydrogen bonding: bond distances, bond energies, and solvent effects

On the basis of recently synthesized calix[4]hydroquinone (CHQ) nanotubes which were self-assembled with infinitely long one-dimensional (1-D) short hydrogen bonds (SHB), we have investigated the nature of 1-D SHB using first-principles calculations for all the systems including the solvent water. The H-bonds relay (i.e., contiguous H-bonds) effect in CHQs shortens the H...O bond distances significantly (by more than 0.2 A) and increases the bond dissociation energy to a large extent (by more than approximately 4 kcal/mol) due to the highly enhanced polarization effect along the H-bond relay chain. The H-bonds relay effect shows a large increase in the chemical shift associated with the SHB. The average binding energies for the infinite 1-D H-bond arrays of dioles and dions increase by approximately 4 and approximately 9 kcal/mol per H-bond, respectively. The solvent effect (due to nonbridging water molecules) has been studied by explicitly adding water molecules in the CHQ tube crystals. This effect is found to be small with slight weakening of the SHB strength; the H...O bond distance increases only by 0.02 A, and the average binding energy decreases by approximately 1 kcal/mol per H-bond. All these results based on the first-principles calculations are the first detailed analysis of energy gain by SHB and energy loss by solvent effect, based on a partitioning scheme of the interaction energy components. These reliable results elucidate not only the self-assembly phenomena based on the H-bond relay but also the solvent effect on the SHB strength.