Watson–Crick versus imidazopyridopyrimidine base pairs: theoretical study on differences in stability and hydrogen bonding strength

Matsuda and coworkers demonstrated that imidazopyridopyrimidine nucelobases (N ^N , O ^O , N ^O , tO ^O , and O ^N ) can mimic Watson–Crick nucleobase in forming H-bonds in DNA double helix. In the present study, we address the question about the strengths of the H-bonds in imidazopyridopyrimidine base pairs compared to those in Watson–Crick ones by focusing particularly on the nature of these interactions. Optimized structures of imidazopyridopyrimidine, imidazopyridopyrimidine–Watson–Crick, and Watson–Crick base pairs are obtained at the DFTB3LYP/6-311++G (d,p). The nature and strength of the intramolecular H-bonds in these base pairs have been investigated based on natural bond orbital (NBO method) to consider the effect of charge transfer, “atoms-in-molecules” (AIM) topological parameters, and decomposition of the interaction energies using the energy decomposition analysis (EDA). These investigations imply that N ^N –O ^O and N ^O –O ^N can form base pairs with four H-bonds (most stable than those of Watson–Crick base pairs) when they incorporated into DNA double helix. Furthermore, it can be deduced that O ^N and N ^N nucleobases form energetically more favorable pairs with adenine and guanine than the normal Watson–Crick counter parts. These results can be helpful for the stabilization and regulation of a variety of new base-pairing motif of DNA structures.     

The effect of CH<Subscript>3</Subscript>, F and NO<Subscript>2</Subscript> substituents on the individual hydrogen bond energies in the adenine–thymine and guanine–cytosine base pairs

The substituent effects on the geometrical parameters and the individual hydrogen bond (HB) energies of base pairs such as X–adenine–thymine (X–A–T), X–thymine–adenine (X–T–A), X–guanine–cytosine (X–G–C), and X–cytosine–guanine (X–C–G) have been studied by the quantum mechanical calculations at the B3LYP and MP2 levels with the 6–311++G(d,p) basis set. The electron withdrawing (EW) substituents (F and NO₂) increase the total binding energy (ΔE) of X–G–C derivatives and the electron donating (ED) substituent (CH₃) decreases it when they are introduced in the 8 and 9 positions of G. The effects of substituents are reversed when they are located in the 1, 5, and 6 positions of C, with exception of CH₃ in the 1 position and F in the 5 position, which in both cases the ΔE value decreases negligibly small. With minor exceptions (X=8–CH₃, 8–F, and 9–NO₂), both ED and EW substituents increase slightly the ΔE values of X–A–T derivatives. The individual HB energies (∆E _HBs) have been estimated using electron densities that calculated at the hydrogen bond critical points (HBCPs) by the atoms in molecules (AIM) method. Most of changes of individual HBs are in consistent with the ED/EW nature of substituents and the role of atoms entered H-bonding. The remarkable change is observed for NO₂ substituted derivative in each case.     

Dimerization of HNO in aqueous solution: an interplay of solvation effects, fast acid-base equilibria, and intramolecular hydrogen bonding?

The recent unraveling of the rather complex acid-base equilibrium of nitroxyl (HNO) has stimulated a renewed interest in the significance of HNO for biology and pharmacy. HNO plays an important role in enzymatic mechanisms and is discussed as a potential therapeutic agent against heart failure. A cumbersome property for studying HNO reactions, its fast dimerization leading to the rapid formation of N(2)O, is surprisingly far from being well understood. It prevents isolation and limits intermediate concentrations of nitroxyl in solution. In this study, a new mechanism for the HNO dimerization reaction in aqueous solution has been theoretically derived on the basis of DFT calculations. Detailed analysis of the initial reaction step suggests a reversal of the cis-trans isomer preference in solution compared to the corresponding gas phase reaction. In contrast to a gas phase derived model based on intramolecular rearrangement steps, an acid-base equilibrium model is in agreement with previous experimental findings and, moreover, explains the fundamental differences between the well studied gas phase reaction and the solvent reaction in terms of polarity, cis-trans isomerizations, and acidities of the intermediates. In the case of cis-hyponitrous acid, the calculated pK(a) values of the acid-base equilibria were found to be significantly different from the corresponding experimental value of the stable trans isomer. Under physiological conditions, N(2)O formation is dominated by the decomposition of the unstable monoanion cis-N(2)O(2)H(-) rather than that of the commonly stated cis-HONNOH.     

A nucleic acid base derivative tethered to a ruthenium carbene complex: hydrogen bonded dimers in both the solid state and solution?

A ruthenium carbene bearing a uracil (Ur) substituent has been prepared and has a dimeric structure in the solid state-the dimer being held together by hydrogen bonds between two uracil groups on neighbouring molecules: evidence for the persistence of this interaction in solution has been obtained.     

Mechanism of the acid-promoted intramolecular schmidt reaction: theoretical assessment of the importance of lone pair-cation, cation-π, and steric effects in controlling regioselectivity

The mechanism of the acid-catalyzed intramolecular Schmidt reaction of 2-azidopropylcyclohexanones was studied using density functional theory (primarily M06-2X). The reaction was found to proceed through rapid formation of azidohydrin intermediates followed by rate-determining concerted N(2)-loss/shift of the alkyl group antiperiplanar to the N(2) leaving group. For cases where steric, lone pair-cation, and cation-π effects have been invoked previously as regiocontrol elements, the origins and magnitudes of these effects have been examined theoretically.     

Hydrogen Atom Tunneling in a Fluorene–Acridine System: Effect of the Reactant Reorganization

A number of two-dimensional potential-energy surfaces are calculated for the hydrogen atom transfer in a fluorene–acridine system at different distances between the reactants. An optimum reactant configuration, at which the potential barrier for chemical reactions is minimum, is found. The corresponding reactant reorganization energy is computed and its importance to the rate constant determination is shown. Effect of various promoting vibrations (translational, librational, intramolecular) on the rate constant and its temperature dependence is analyzed. Theory is compared to the literature and experimental data and good agreement is obtained.     

Role of the base and endogenous anions in “ligand-free” catalytic systems for the Suzuki–Miyaura reaction

UV spectroscopic studies combined with kinetic measurements for the Suzuki–Miyaura reaction catalyzed by “ligand-free” catalytic systems have demonstrated that the base is involved in the formation of the palladium complexes ensuring the occurrence of the transmetalation stage. It follows from UV monitoring data for the catalytic reaction involving aryl iodides that a considerable part of palladium during the process is in the form of Pd²⁺ acid complexes with endogenous anions and does not participate in the main catalytic cycle.     

Solvent effects on the molecular stability,intramolecular hydrogen bond,and π-electron delocalization in the simple RAHB systems with different donors and acceptors: a quantum chemical study

Structural Chemistry - In the present study, solvent effects on the molecular stability, intramolecular hydrogen bond (IMHB), and π-electron delocalization (π-ED) in some of the simple...     

Effects of bulky substituent groups on the Si–Si triple bonding in RSiSiR and the short Ga–Ga distance in Na2[RGaGaR]: A theoretical study

The steric and electronic effects of bulky aryl and silyl groups on the Si–Si triple bonding in RSiSiR and the short Ga–Ga distance in Na₂[RGaGaR] are investigated by density functional calculations. As typical bulky groups, Tbt = C₆H₂-2,4,6-{CH(SiMe₃)₂}₃, Ar′ = C₆H₃-2,6-(C₆H₃-2,6-iPr₂)₂, Ar¹ = C₆H₃-2,6-(C₆H₂-2,4,6-iPr₃)₂, SiMe(SitBu₃)₂, and SiiPrDis₂ (Dis = CH(SiMe₃)₂) are investigated and characterized. The importance of large basis sets is emphasized for density functional calculations.     

Is the DPT tautomerization of the long A·G Watson–Crick DNA base mispair a source of the adenine and guanine mutagenic tautomers? A QM and QTAIM response to the biologically important question

Herein, we first address the question posed in the title by establishing the tautomerization trajectory via the double proton transfer of the adenine·guanine (A·G) DNA base mispair formed by the canonical tautomers of the A and G bases into the A*·G* DNA base mispair, involving mutagenic tautomers, with the use of the quantum‐mechanical calculations and quantum theory of atoms in molecules (QTAIM). It was detected that the A·G ? A*·G* tautomerization proceeds through the asynchronous concerted mechanism. It was revealed that the A·G base mispair is stabilized by the N6H···O6 (5.68) and N1H···N1 (6.51) hydrogen bonds (H‐bonds) and the N2H···HC2 dihydrogen bond (DH‐bond) (0.68 kcal·mol^?1), whereas the A*·G* base mispair—by the O6H···N6 (10.88), N1H···N1 (7.01) and C2H···N2 H‐bonds (0.42 kcal·mol^?1). The N2H···HC2 DH‐bond smoothly and without bifurcation transforms into the C2H···N2 H‐bond at the IRC = ?10.07 Bohr in the course of the A·G ? A*·G* tautomerization. Using the sweeps of the energies of the intermolecular H‐bonds, it was observed that the N6H···O6 H‐bond is anticooperative to the two others—N1H···N1 and N2H···HC2 in the A·G base mispair, while the latters are significantly cooperative, mutually strengthening each other. In opposite, all three O6H···N6, N1H···N1, and C2H···N2 H‐bonds are cooperative in the A*·G* base mispair. All in all, we established the dynamical instability of the А*·G* base mispair with a short lifetime (4.83·10^?14 s), enabling it not to be deemed feasible source of the A* and G* mutagenic tautomers of the DNA bases. The small lifetime of the А*·G* base mispair is predetermined by the negative value of the Gibbs free energy for the A*·G* → A·G transition. Moreover, all of the six low‐frequency intermolecular vibrations cannot develop during this lifetime that additionally confirms the aforementioned results. Thus, the A*·G* base mispair cannot be considered as a source of the mutagenic tautomers of the DNA bases, as the A·G base mispair dissociates during DNA replication exceptionally into the A and G monomers in the canonical tautomeric form. © 2013 Wiley Periodicals, Inc.     

Infrared study of the hydrogen bonding site in a poly-functional schiff base: N(sp2) or N(sp)?

The hydrogen bond complexes between phenol derivatives and the Schiff base [(diphenylmethylene)amino]-acetonitrile have been studied by infrared spectroscopy in carbon tetrachloride solution. The thermodynamic data and the infrared spectra investigated in the ν_OH, ν_CN and ν_CN region indicate that complex formation occurs at the nitrogen atom of the nitrile function. The hydrogen bonding site is in this case governed by the accessibility of the lone pair which is markedly higher for the N(sp) than the N(sp²) electrons.     

Variationally determined electronic states for the theoretical analysis of intramolecular interaction: I. Resonance energy and rotational barrier of the C–N bond in formamide and its analogs

We present a new method that produces a variationally determined zeroth-order wave function for the analysis of intramolecular interactions between the fragments of a molecule. In our method, called the space-restricted wave function (SRW) method, this wave function is defined with nonorthogonal orbitals, which are obtained using the appropriately restricted variational spaces. The wave function thus obtained represents the electronic state with the target interactions deactivated, and it is constructed without unnecessarily breaking bonds, in contrast to some of the existing methods. Furthermore, we can perform energy decomposition analysis of intramolecular interactions using the zeroth-order functions that the SRW method yields. The validity of the SRW method is demonstrated in the analysis of the resonance energy and the rotational barrier of the C–N bond in formamide and its analogs. This method gives energy components that are different from those given by existing methods. With these components, we elucidate the origin of the rotational barrier from another point of view. Our SRW method gives meaningful results for the investigation of electron behavior and the nature of the molecular system.     

Tetra-hydrides of the third-row transition elements: spin–orbit coupling effects on geometrical deformation in WH4 and OsH4

The dissociation energies of MH₄ (M =  La, Hf–Hg) were computed using full optimized reaction space (FORS) multi-configuration self-consistent field (MCSCF) and second-order multi-reference Møller–Plesset perturbation methods with the SBKJC basis sets augmented by a set of polarization functions (SBKJC(f,p)). It was shown that of the molecules examined, only four tetra-hydrides HfH₄, TaH₄, WH₄, and OsH₄ with T_d symmetry are lower in energy than the corresponding dissociation limits. For WH₄ and OsH₄, the potential energy surfaces from the D_4h to the T_d structure were explored from both theoretical calculations and symmetry arguments based on the pseudo-Jahn- Teller effect. As for WH₄, it is found that the ground state could be ³E_g, ³A_2g, or ³B_2g at the D_4h structure. The present calculations suggest that the ground state is ³E_g, and that this state is stabilized by the e_u deformation into a C_2v structure (³B₁) and then sequentially to the most stable T_d structure (³A₂). If the molecular system is promoted to the lowest ³B_2g state, the D_4h structure can directly deform into the most stable T_d structure along the b_2u vibrational mode. For OsH₄, the ground state (⁵B_1g) at the D_4h structure deforms into a D_2d structure and the resulting ⁵B₂ state strongly interacts with the lowest ³E and ¹A₁ states due to the spin-orbit couplings (SOCs). As a result, it was shown that the relativistic potential energy of the lowest spin-mixed state (ground state) monotonically decreases along the D_2d deformation path from the D_4h to the T_d structure.     

Structure and bonding in the isoelectronic series CnHnP5-n+: is phosphorus a carbon copy?

The relative stabilities of different isomers of the isoelectronic series C(n)H(n)P(5-n)(+) have been investigated using G3X theory. The results indicate that all species containing one or more phosphorus atom adopt a three-dimensional nido geometry, in marked contrast to the planar structure favoured by the all-carbon analogue. Within isomeric nido clusters, a strong correlation between total energy and the nucleus-independent chemical shift (NICS) indicates that three-dimensional aromaticity plays a significant role in determining the stability of the cluster. In the context of these nido clusters, the extent to which phosphorus is a carbon copy proves to be highly dependent on the global electronic environment. The first isolobal substitution of CH by P causes a complete switch from localised to delocalised bonding, accompanied by a transition from a two- to a three-dimensional structure, with the phosphorus atom showing a strong preference for the unique apical site. In contrast, further increasing the phosphorus content causes no further change in structure or bonding, suggesting that, at the basal sites, phosphorus is a rather better carbon copy. The low-energy pathways for interconversion of apical and basal atoms previously identified in C(2)H(2)P(3)(+) prove to be a general feature of all members of the series.     

Interaction of Functionalized Naphthalenophanes with Abasic Sites in DNA: DNA Cleavage,DNA Cleavage Inhibition,and Formation of Ligand–DNA Adducts

Ligands interacting with abasic (AP) sites in DNA may generate roadblocks in base-excision DNA repair (BER) due to indirect inhibition of DNA repair enzymes (e.g., APE1) and/or formation of toxic byproducts, resulting from ligand-induced strand cleavage or covalent cross-links. Herein, a series of 12 putative AP-site ligands, sharing the common naphthalenophane scaffold, but endowed with a variety of substituents, have been prepared and systematically studied. The results demonstrate that most naphthalenophanes bind to AP sites in DNA and inhibit the APE1-induced hydrolysis of the latter in vitro. Remarkably, their APE1 inhibitory activity, as characterized by IC₅₀ and K_I values, can be directly related to their affinity and selectivity to AP sites, as assessed by means of fluorescence melting experiments. On the other hand, the molecular design of naphthalenophanes has a crucial influence on their intrinsic AP-site cleavage activity (i.e., ligand-catalyzed β- and β,δ-elimination reactions at the AP site), as illustrated by the compounds either having an exceptionally high AP-site cleavage activity (e.g., 2,7-BisNP-S , 125-fold more efficacious than spermine) or being totally devoid of this activity (four compounds). Finally, the unprecedented formation of a stable covalent DNA adduct upon reaction of one ligand ( 2,7-BisNP-NH ) with its own product of the AP-site cleavage is revealed.