Quantum chemical study of the hydrogen‐bonded patterns in A · T base pair of DNA: Origins of tautomeric mispairs,base flipping,and Watson–Crick ⇒ Hoogsteen conversion

The current work aims to thoroughly investigate a variety of facets of the hydrogen‐bond pattern of the Watson–Crick A · T base pair of DNA. It offers a novel mechanism of the origin of the hydrogen‐bonded mispairing in the A · T base pair based on the analysis of the lower‐energy portion of the total potential energy surface of all possible rearrangements of the hydrogen‐bond patterns in this pair, performed at the Hartree–Fock (HF), second‐order Moller–Plesset (MP2)//HF, and B3LYP computational levels in conjunction with 6‐31+G(d) basis set. The specific novelty of this mechanism is that the primary step consists of a single proton transfer along the N₃(T)–H … N₁ (A) hydrogen bond, thus leading to a transition state that is not directly related to the proton transfer. Rather, it governs the interbase shift within the A · T pair switching the hydrogen‐bonded pattern and then separating the normal A · T pair from the mispairing valley on its potential energy surface. The latter comprises three mismatched base pairs, easily converted to each other because of lower barriers (≈1 kcal/mol) of the corresponding proton transfers. It is demonstrated that, in terms of the Gibbs free energy taken at room T = 298.15 K, the most stable mispair in such valley is predicted to be less stable by 9.7 ± 2 kcal/mol than the Watson–Crick pair, thus implying that the spontaneous point mutations of this type occur as infrequently as to be characterized by an equilibrium constant of 10^?6 to 10^?9. This estimate falls into the well‐known experimental range of mutation frequency per base pair. The structure of a so‐called “base flipping” of the A · T base pair, originated from a breaking of its N₃(T)‐H … N₁ (A) hydrogen bond, is also found and reported in the current work for the first time. The transition state A · T ${}_{\text{ts}}^{\text{WC?H}}$ , which governs the conversion of the Watson–Crick pair of adenine · thymine into the Hoogsteen one and is related to a breaking of the N₆(A)–H … O₄(T), is also obtained and its energetical and geometrical features are discussed. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem, 2003     

Struktur und Eigenschaften des Hydridomethyltetrafluorphosphatanions, [CH3PF4H]—

Structure and Properties of the Hydridomethyltetrafluorophosphate Anion, [CH₃PF₄H]^— Methyltrifluorphosphorane reacts with strong fluoride donors like CsF, (CH₃)₄NF and (CH₃)₄PF with formation of the corresponding hydridomethyltetrafluorophosphates. The salts are characterized by NMR, IR and Raman spectroscopy. The experimental results show that only the trans isomer is formed. For both isomers theoretical calculations (B3LYP/6‐31+G* and RHF/6‐31+G*) were carried out. The difference for the Gibbs free energy between the isomers was calculated to be 35.4 kJ/mol (B3LYP/6‐31+G*). The RHF/6‐31+G* calculation yields, for the almost octahedral trans isomer, bond distances of r(PF) = 167 pm, r(PC) = 184.5 pm and r(PH) = 138.1 pm.     

Infrared Spectroscopic Observation of a G–C+ Hoogsteen Base Pair in the DNA:TATA‐Box Binding Protein Complex Under Solution Conditions

Hoogsteen DNA base pairs (bps) are an alternative base pairing to canonical Watson–Crick bps and are thought to play important biochemical roles. Hoogsteen bps have been reported in a handful of X‐ray structures of protein–DNA complexes. However, there are several examples of Hoogsteen bps in crystal structures that form Watson–Crick bps when examined under solution conditions. Furthermore, Hoogsteen bps can sometimes be difficult to resolve in DNA:protein complexes by X‐ray crystallography due to ambiguous electron density and by solution‐state NMR spectroscopy due to size limitations. Here, using infrared spectroscopy, we report the first direct solution‐state observation of a Hoogsteen (G–C⁺) bp in a DNA:protein complex under solution conditions with specific application to DNA‐bound TATA‐box binding protein. These results support a previous assignment of a G–C⁺ Hoogsteen bp in the complex, and indicate that Hoogsteen bps do indeed exist under solution conditions in DNA:protein complexes.     

A Highly Stabilizing Silver(I)‐Mediated Base Pair in Parallel‐Stranded DNA

The first parallel‐stranded DNA duplex with Hoogsteen base pairing that readily incorporates an Ag⁺ ion into an internal mispair to form a metal‐mediated base pair has been created. Towards this end, the highly stabilizing 6 FP ‐Ag⁺‐ 6 FP base pair comprising the artificial nucleobase 6‐furylpurine ( 6 FP ) was devised. A combination of temperature‐dependent UV spectroscopy, CD spectroscopy, and DFT calculations was used to confirm the formation of this base pair. The nucleobase 6 FP is capable of forming metal‐mediated base pairs both by the Watson–Crick edge (i.e. in regular antiparallel‐stranded DNA) and by the Hoogsteen edge (i.e. in parallel‐stranded DNA), depending on the oligonucleotide sequence and the experimental conditions. The 6 FP ‐Ag⁺‐ 6 FP base pair within parallel‐stranded DNA is the most strongly stabilizing Ag⁺‐mediated base pair reported to date for any type of nucleic acid, with an increase in melting temperature of almost 15 °C upon the binding of one Ag⁺ ion.     

Theoretical investigation on multinuclear NMR chemical shifts of some tris(trifluoromethyl)boron complexes

Tris(trifluoromethyl)boron complexes have unusual properties and may find applications in many fields of chemistry, biology, and physics. To gain insight into their NMR properties, the isotropic ¹¹B, ¹³C, and ¹⁹F NMR chemical shifts of a series of tris(trifluoromethyl)boron complexes were systematically studied using the gauge‐included atomic orbitals (GIAO) method at the levels of B3LYP/6‐31 + G(d,p)//B3LYP/6‐31G* and B3LYP/6‐311 + G(d,p)//B3LYP/6‐311 + G(d,p). Solvent effects were taken into account by polarizable continuum models (PCM). The calculated results were compared with the experimental values. The reason that the structurally inequivalent fluorine atoms in a specific species give a same chemical shift in experimental measurements is attributed to the fast rotation of CF₃ group around the B? C(F₃) bond because of the low energy barrier. The calculated ¹¹B, ¹³C(F₃), and ¹⁹F chemical shifts are in good agreement with the experimental measurements, while the deviations of calculated ¹³C(X, X = O, N) chemical shifts are slightly large. For the latter, the average absolute deviations of the results from B3LYP/6‐311 + G(d,p)//B3LYP/6‐311 + G(d,p) are smaller than those from B3LYP/6‐31 + G(d,p)//B3LYP/6‐31G*, and the inclusion of PCM reduces the deviation values. The calculated ¹⁹F and ¹¹B chemical shieldings of (CF₃)₃BCO are greatly dependent on the optimized structures, while the influence of structural parameters on the calculated ¹³C chemical shieldings is minor. Copyright © 2009 John Wiley & Sons, Ltd.     

2-丁基-四氢噻吩亚砜13C-NMR的理论研究

在RHF/6-31G和B3LYP/6-31G水平上对顺式(Cis-)与反式(Trans-)2-丁基-四氢噻吩亚砜(BTHTO)进行几何优化,应用规范不变原子轨道法(GIAO)在6-31G、6-31+G、6-31++G和6-31+G(2d,p)水平上计算了Cis-和Trans-BTHTO的13C-NMR,对13C-NMR谱进行了归属。结果表明,BTHTO噻吩五元环的稳定构象呈半椅式,Cis-和Trans-BTHTO中与硫原子直接碳原子13C-NMR的显著差异主要是由于空间构型不同引起分子的静电势场对相应碳原子的屏蔽作用不同所致。     

Comparative studies between hydrated hydrogen bonded and stacked DNA base pair

Influence of hydration on the Watson–Crick guanine–cytosine hydrogen bonded (h-bonded) base pair (GC) and stacked pair (G/C) was investigated in their first hydration shell. An electrostatic based approach has been used to identify the potential binding sites for water molecules around GC and G/C pairs. Several geometries of the complexes, GC…(H₂O)_n and G/C…(H₂O)_n (n=1–6) were investigated using HF/6-31G** and HF/6-31G++** methods. Further minimization calculations were performed at both B3P86/6-31G** and MP2/6-31G** levels to assess the role of electron correlation contribution in the hydration process. It can be concluded from the present findings that the stacked base-pair hydrate better than the corresponding h-bonded base pair, and DNA base pairs can accommodate up to 4–5 water molecules whereas stacked pair do accommodate 5–6 water molecules.     

Chemical Reactivity of Oxo‐ and Aza‐γ‐lactam Rings

Different mechanisms for the alkaline hydrolysis of oxo and aza‐γ‐lactam rings have been studied by ab initio calculations at the MP2/6‐31+G*//MP2/6‐31+G* and B3LYP/6‐31+G*//B3LYP/6‐31+G* levels. The tetrahedral intermediate can undergo two different reactions, the cleavage of the C₂−N₂ bond (the classical mechanism) and the cleavage of the C₂−X₆ bond (X=O, N). Both compounds present similar energy barriers for the classical fragmentation, and show considerably lower barriers for the alternative mechanism. Because of this reactivity, the compounds studied are expected to be β‐lactamase inhibitors.     

1. 5-环辛二烯-3, 7-二炔(C~8H~4)结构和光谱性质的理论研究

采用量子化学从头算方法研究了1,5-环辛二烯-3,7-二炔(C~8H~4)的结构和光谱性质,根据等键反应分析和自然键轨道方法研究了它的稳定性、成键情况和共轭性。结果表明1,5-环辛二烯-3,7-二炔(C~8H~4)分子为平面刚性结构,可能稳定存在。分子中C≡C键与C=C键存在一定程度的共轭,可能具有芳香性。     

Molecular structure, IR spectra of 2-mercaptobenzothiazole and 2-mercaptobenzoxazole by density functional theory and ab initio Hartree–Fock calculations

Quantum chemistry calculations have been performed using Gaussian03 program to compute optimized geometry, harmonic vibrational frequency along with intensities in IR and Raman spectra and atomic charges at RHF/6-31+G*, B3LYP/6-31+G* and B3LYP/6-31++G* levels for 2-mercaptobenzothiazole (MBT, C₇H₅NS₂) and 2-mercaptobenzoxazole (MBO, C₇H₅NOS) in the ground state. The scaled harmonic vibrational frequencies have been compared with experimental FT-IR and FT-Raman spectra. The results show that the scaled theoretical vibrational frequencies is very good agreement with the experimental values. A detailed interpretation of the infrared and Raman spectra of 2-mercaptobenzothiazole and 2-mercaptobenzoxazole was reported. Comparison of calculated spectra with the experimental spectra provides important information about the ability of the computational method to describe the vibrational modes.     

Reaching for two new stable ambiphilic quinoline‐derived N‐heterocyclic carbenes at DFT level

A detailed investigation on the thermodynamic and kinetic stability of four carbenic tautomers of quinoline 1 , including quinoline‐2‐ylidene 2 , quinoline‐3‐ylidene 3 , quinoline‐4‐ylidene 4 , and 3,4‐dihydroquinoline‐4‐ylidene 5 , reveals that singlet planar six‐membered ring N‐heterocyclic carbenes (NHCs) 2 and 4 have less stability than Arduengo type NHC but seems to have enough conceivably for reaching at B3LYP/aug‐cc‐pVTZ//B3LYP/6–31+G* and B3LYP/6–311++G**//B3LYP/6–31+G* levels. All these six‐membered NHCs are extremely ambiphilic with the more nucleophilic and electrophilic characters compared to the Arduengo type one. The aromaticity of singlet 2 and 4 is a significant contributor to their stability which is confirmed through their Nucleus‐independent chemical shift(1)_zz values. Finally, among 2–5 , the normal NHC 2 is thermodynamically preferred but the remote NHC 4 is kinetically proffered over the other isomeric carbenes. The effects of different N‐ or C‐substituted NHCs of 2 are studied using appropriate isodesmic reactions. The trimethylsilyl substituent exhibits slightly larger carbene stabilization in quinoline‐derived NHCs than the pyridine analogue. © 2014 Wiley Periodicals, Inc.     

Ultraviolet Absorption Induces Hydrogen‐Atom Transfer in G⋅C Watson–Crick DNA Base Pairs in Solution

Ultrafast deactivation pathways bestow photostability on nucleobases and hence preserve the structural integrity of DNA following absorption of ultraviolet (UV) radiation. One controversial recovery mechanism proposed to account for this photostability involves electron‐driven proton transfer (EDPT) in Watson–Crick base pairs. The first direct observation is reported of the EDPT process after UV excitation of individual guanine–cytosine (G?C) Watson–Crick base pairs by ultrafast time‐resolved UV/visible and mid‐infrared spectroscopy. The formation of an intermediate biradical species (G[?H]?C[+H]) with a lifetime of 2.9 ps was tracked. The majority of these biradicals return to the original G?C Watson–Crick pairs, but up to 10 % of the initially excited molecules instead form a stable photoproduct G*?C* that has undergone double hydrogen‐atom transfer. The observation of these sequential EDPT mechanisms across intermolecular hydrogen bonds confirms an important and long debated pathway for the deactivation of photoexcited base pairs, with possible implications for the UV photochemistry of DNA.     

Theoretical Study on Gas—phase Pyrolytic Reactions of N—Ethyl,Isopropyl and N—t—Butyl Substituted 2—Aminopyrazine

Density functional theory (DFT) and ab initio methods were used to study gas‐phase pyrolytic reaction mechanisms of iV‐ethyl, N‐isopropyl and N‐t‐butyl substituted 2‐aminopyrazine at B3LYP/6–31G* and MP2/6–31G*, respectively. Single‐point energies of all optimized molecular geometries were calculated at B3LYP/6–311 + G(2d,p) level. Results show that the pyrolytic reactions were carried out through a unimolecular first‐order mechanism which were caused by the migration of atom H(17) via a six‐member ring transition state. The activation energies which were verified by vibrational analysis and correlated with zero‐point energies along the reaction channel at B3LYP/6–311 + G(2d,p) level were 252.02 kJ. mo^?1 (N‐ethyl substituted), 235.92 kJ‐mol^?1 (N‐t‐isopropyl substituted) and 234.27 kJ‐mol^?1 (N‐t‐butyl substituted), respectively. The results were in good agreement with available experimental data.     

Theoretical studies on the conformations of selenamides

Ab initio HF/6-31+G*, MP2/6-31+G*, B3LYP/6-31+G* level calculations have been performed on HSe-NH₂ to estimate the Se-N rotational barriers and N-inversion barriers. Two conformers have been found withsyn andanti arrangement of the NH₂ hydrogens with respect to Se-H bond. The N inversion barriers in selenamide are 1.65, 2.47, 1.93 kcal/mol and the Se-N rotational barriers are 6.58, 6.56 and 6.12 kcal/mol respectively at HF/6-31+G*, MP2/6-31+G* and B3LYP/6-31+G* levels respectively. The n_N →Σ *_Se-H negative hyperconjugation is found to be responsible for the higher rotational barriers.     

Covalently Cross-Linked Watson–Crick Base Pair Models

Structural characteristics of Watson–Crick hydrogen-bonded base pairs are displayed by methylene-bridged base pairs of type A . The shown superposition of the X-ray structure obtained for the base pair A (Rib¹=Et; Rib²=Me) over that of a C–G base pair illustrates that A occupies an area similar to that occupied by a traditional Watson–Crick hydrogen-bonded base pair. Temperature-dependent ¹H NMR studies indicate that the energy barrier for rotation along its CH₂ bridge is about 10 kcal mol⁻¹, and that it exists predominantly in one conformer at −70°C.     

Novel H-bonded base dimers as repeat units for information-bearing self-associative duplexes: a B3LYP/6-31G* search

Density functional theory at the B3LYP/6-31G* level with counterpoise correction has been employed to study six sets of nitrogenous bases for the capacity of each to form H-bonded dimers restricted to a chosen pairing configuration. These results are augmented by MP2/6-311++G(d,p) single point calculations on the B3LYP/6-31G* optimized geometries. Each set has two bases, including substituted azoles, imidazoles, pyrimidines, and fused ring systems. This study aims to determine the suitability of each set to furnish H-bonded base pairs which may serve as repeat units for self-associative H-bonded macromolecular duplexes with the capacity to store and replicate information at the molecular level. Out of the various possibilities tested here, a set of two substituted pyrimidines best satisfies the prescribed criteria and may be put forward as a good candidate to yield isomorphic repeat units for designing such synthetic information-bearing macromolecular duplexes. The optimized configurations of these chosen base pairs as calculated at the B3LYP/6-31G* level compare well with those calculated at the B3LYP/6-31++G(d,p) and MP2/6-31G(d,p) levels, and indicate that isomorphism of the two base pairs is independent of method used. Assuming a one-to-one correspondence for encoding information in the macromolecule, such a set of two bases can allow the macromolecule to encode up to 8 types of encrypted species.     

Interaction of singlet oxygen and superoxide radical anion with guanine and formation of its mutagenic modification 8‐oxoguanine

Formation of 8‐oxoguanine (8OG) from guanine in biological systems is known to cause lethal mutation and cancer. It has been suggested earlier, on the basis of experimental studies, that the oxygen molecule in its lowest singlet excited state (¹O₂) plays an important role in the formation of 8OG. In order to understand the possible mechanisms in this context, B3LYP/6‐31+G* and MP2/6‐31+G* calculations were carried out on the structures and stabilities of different molecules and complexes involved in the formation of 8OG. All the molecules, complexes, and transition states studied in the present report were solvated in aqueous media. Guanine has been found to make a strong complex with ¹O₂ with the latter species located above the imidazole ring plane, and the complex of guanine with ³O₂ is much weaker than that with ¹O₂. Transition state calculations were carried out to study formation of 7,8‐dihydro,8‐hydroxyguanine (8OHG) and 2‐oxo‐imidazole. It has been shown that 8OG can be formed in two different ways: (i) due to interaction of the radical cation of guanine with O where 8OHG complexed with ¹O₂ would occur as an intermediate, and (ii) due to interaction of guanine with ¹O₂ leading to the formation of guanine hydroperoxide that would react with a water molecule in the presence of two ¹O₂ molecules serving as a source of energy to overcome the barrier. It is shown that because the interaction strengths of ³O₂ and ¹O₂ with other molecules, e.g., guanine, are very different, a crossing of their potential energy surfaces takes place in both gas phase and aqueous media, as a result of which the lifetime of ¹O₂ is strongly decreased. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2005     

Contiguous metal-mediated base pairs comprising two Ag(I) ions

The incorporation of transition‐metal ions into nucleic acids by using metal‐mediated base pairs has proved to be a promising strategy for the site‐specific functionalization of these biomolecules. We report herein the formation of Ag⁺‐mediated Hoogsteen‐type base pairs comprising 1,3‐dideaza‐2′‐deoxyadenosine and thymidine. By defunctionalizing the Watson–Crick edge of adenine, the formation of regular base pairs is prohibited. The additional substitution of the N3 nitrogen atom of adenine by a methine moiety increases the basicity of the exocyclic amino group. Hence, 1,3‐dideazaadenine and thymine are able to incorporate two Ag⁺ ions into their Hoogsteen‐type base pair (as compared with one Ag⁺ ion in base pairs with 1‐deazaadenine and thymine). We show by using a combination of experimental techniques (UV and circular dichroism (CD) spectroscopies, dynamic light scattering, and mass spectrometry) that this type of base pair is compatible with different sequence contexts and can be used contiguously in DNA double helices. The most stable duplexes were observed when using a sequence containing alternating purine and pyrimidine nucleosides. Dispersion‐corrected density functional theory calculations have been performed to provide insight into the structure, formation and stabilization of the twofold metalated base pair. They revealed that the metal ions within a base pair are separated by an Ag???Ag distance of about 2.88 Å. The Ag–Ag interaction contributes some 16 kcal mol^?1 to the overall stability of the doubly metal‐mediated base pair, with the dominant contribution to the Ag–Ag bonding resulting from a donor–acceptor interaction between silver 4d‐type and 4s orbitals. These Hoogsteen‐type base pairs enable a higher functionalization of nucleic acids with metal ions than previously reported metal‐mediated base pairs, thereby increasing the potential of DNA‐based nanotechnology.     

Theoretical Study of the Alkaline Hydrolysis of Tricyclic Carbapenem

Alkaline hydrolysis is a good test to evaluate the properties of β‐lactam compounds and derivatives. In this work, a RHF/6‐31+G*//RHF/6‐31+G* theoretical study of the mechanism controlling the alkaline hydrolysis of sanfetrinem was conducted. The geometric properties of this compound are consistent with an intrinsic reactivity similar to that of other β‐lactams including penicillins and cephalosporins. Also, similarly to cephalosporins, the MeO group provides an alternative route for the hydrolysis mechanism.