Effect of the Solvent and Substituent on Tautomeric Preferences of Amine-Adenine Tautomers.

Adenine is one of the basic molecules of life; it is also an important building block in the synthesis of new pharmaceuticals, electrochemical (bio)sensors, or self-assembling molecular materials. Therefore, it is important to know the effects of the solvent and substituent on the electronic structure of adenine tautomers and their stability. The four most stable adenine amino tautomers (9H, 7H, 3H, and 1H), modified by substitution (C2- or C8-) of electron-withdrawing NO2 and electron-donating NH2 groups, are studied theoretically in the gas phase and in solvents of different polarities (1 ≤ ε < 109). Solvents have been modeled using the polarizable continuum model. Comparison of the stability of substituted adenine tautomers in various solvents shows that substitution can change tautomeric preferences with respect to the unsubstituted adenine. Moreover, C8 substitution results in slight energy differences between tautomers in polar solvents (<1 kcal/mol), which suggests that in aqueous solution, C8-X-substituted adenine systems may consist of a considerable amount of two tautomers-9H and 7H for X = NH2 and 3H and 9H for X = NO2. Furthermore, solvation enhances the effect of the nitro group; however, the enhancement strongly depends on the proximity effects. This enhancement for the NO2 group with two repulsive N···ON contacts can be threefold higher than that for the NO2 with one attractive NH···ON contact. The proximity effects are even more significant for the NH2 group, as the solvation may increase or decrease its electron-donating ability, depending on the type of proximity.

Effect of Alkali Metal Cations on Length and Strength of Hydrogen Bonds in DNA Base Pairs.

For many years, non-covalently bonded complexes of nucleobases have attracted considerable interest. However, there is a lack of information about the nature of hydrogen bonding between nucleobases when the bonding is affected by metal coordination to one of the nucleobases, and how the individual hydrogen bonds and aromaticity of nucleobases respond to the presence of the metal cation. Here we report a DFT computational study of nucleobase pairs interacting with alkali metal cations. The metal cations contribute to the stabilization of the base pairs to varying degrees depending on their position. The energy decomposition analysis revealed that the nature of bonding between nucleobases does not change much upon metal coordination. The effect of the cations on individual hydrogen bonds were described by changes in VDD charges on frontier atoms, H-bond length, bond energy from NBO analysis, and the delocalization index from QTAIM calculations. The aromaticity changes were determined by a HOMA index.

Aromaticity Induced by Electric Field: The Case of Polycalicenes.

Local and global π-electron delocalization occurring in planar poly-1,7-[N]calicenes is investigated with use of 10 aromaticity measures based on different physical properties. Systematic change of aromatic character is observed along chains of connected calicene units. Multidimensionality of the aromaticity phenomenon is studied with use of principal component analysis (PCA). The structural characteristics are compared with the properties of the isolated calicene molecule exposed to external electric fields of various intensities. Interrelations between the value of electric field applied and physical properties of the calicene molecule are discussed in the context of calicene unit affected by its surroundings in polycalicene chains. The patterns of global π-electron delocalization are described in graph theory terminology, and interconnections between local and global aromaticity in these systems are established.

Interference of H-bonding and substituent effects in nitro- and hydroxy-substituted salicylaldehydes.

Two intramolecular interactions, i.e., (1) hydrogen bond and (2) substituent effect, were analyzed and compared. For this purpose, the geometry of 4- and 5-X-substituted salicylaldehyde derivatives (X = NO(2), H or OH) was optimized by means of B3LYP/6-311 + G(d,p) and MP2/aug-cc-pVDZ methods. The results obtained allowed us to show that substituents (NO(2) or OH) in the para or meta position with respect to either OH or CHO in H-bonded systems interact more strongly than in the case of di-substituted species: 4- and 3-nitrophenol or 4- and 3-hydroxybenzaldehyde by ~31%. The substituent effect due to the intramolecular charge transfer from the para-counter substituent (NO(2)) to the proton-donating group (OH) is ~35% greater than for the interaction of para-OH with the proton-accepting group (CHO). The total energy of H-bonding for salicylaldehyde, and its derivatives, is composed of two contributions: ~80% from the energy of H-bond formation and ~20% from the energy associated with reorganization of the electron structure of the systems in question.

Hydrogen bonding as a modulator of aromaticity and electronic structure of selected ortho-hydroxybenzaldehyde derivatives.

Properties of hydrogen bonds can induce changes in geometric or electronic structure parameters in the vicinity of the bridge. Here, we focused primarily on the influence of intramolecular H-bonding on the molecular properties in selected ortho-hydroxybenzaldehydes, with additional restricted insight into substituent effects. Static models were obtained in the framework of density functional theory at B3LYP/6-311+G(d,p) level. The electronic structure parameters evolution was analyzed on the basis of Atoms In Molecules (AIM) and Natural Bond Orbitals methods. The aromaticity changes related to the variable proton position and presence of substituents were studied using Harmonic Oscillator Model of Aromaticity (HOMA), Nucleus-Independent Chemical Shift (NICS) and AIM-based parameter of Matta and Hernández-Trujillo. Finally, Car-Parrinello molecular dynamics was applied to study variability of the hydrogen bridge dynamics. The interplay between effects of the substitution and variable position of the bridged proton was discussed. It was found that the hydrogen bond energies are ca. 9-10 kcal/mol, and the bridged proton exhibits some degree of penetration into the acceptor region. The covalent character of the studied hydrogen bond was most observable when the bridged proton reached the middle position between the donor and acceptor regions. The aromaticity indexes showed that the aromaticity of the central phenyl ring is strongly dependent on the bridged proton position. Correlations between these parameters were found and discussed. In the applied time-scale, the analysis of time evolution of geometric parameters showed that the resonance strengthening does not play a crucial role in the studied compounds.

Hydroxyl group as a substituent with varying electronic properties: effect of strength of H-bonding on charge density changes in Ph-OH F⁻ complexes.

Due to gradual and controlled changes of interatomic distances between heavy atoms in OH…F⁻ of C(6)H(5)OH…F⁻ systems it was possible to study the electronic structure evolution. Computation at B3LYP/6-311+G(d,p) level of theory was performed for this purpose. Changes in charges at atoms and characteristics at bond critical points (BCPs) of the H-bond region and also in distant parts of the systems were investigated by means of natural bond orbitals (NBO) and atoms in molecules (AIM) analyses. It is shown that at the border line between partially covalent and non-covalent H-bonding (Espinosa et al. in J Chem Phys 117:5529, 2002; Grabowski et al. in J Phys Chem B 110:6444, 2006) with the H…F interatomic distance ~1.8 Ǻ the hydrogen atom has the most positive charge. In addition, the change in the atomic charge values in the interacting region affects the phenyl ring properties. The decrease of the sum of atomic charges as well as of the aromaticity was noticed when the OH….F distance is shortened.

On the aromatic character of the heterocyclic bases of DNA and RNA.

Studies based on ab initio optimized geometries (at B3LYP/6-311+G** and MP2/6-311+G** levels) and on experimental structures retrieved from the Cambridge Structural Database (CSD) reveal that the nucleobases constituting DNA and RNA differ significantly in their aromatic character, as shown by the geometry-based index of aromaticity HOMA that ranges from 0.466 for thymine to 0.917 for adenine, based on B3LYP/6-311+G** calculations, and 0.495-0.926, respectively, if based on the MP2/6-311+G** level. Aromaticity of the bases decreases markedly with an increase of the number of double-bond C=X (X = N, O) substituents at the rings. H-bonds involving C=O groups in Watson-Crick pairs cause an increase of the aromatic character of the rings.