Nucleic acid reactivity: Challenges for next‐generation semiempirical quantum models

Semiempirical quantum models are routinely used to study mechanisms of RNA catalysis and phosphoryl transfer reactions using combined quantum mechanical (QM)/molecular mechanical methods. Herein, we provide a broad assessment of the performance of existing semiempirical quantum models to describe nucleic acid structure and reactivity to quantify their limitations and guide the development of next‐generation quantum models with improved accuracy. Neglect of diatomic differential overlap and self‐consistent density‐functional tight‐binding semiempirical models are evaluated against high‐level QM benchmark calculations for seven biologically important datasets. The datasets include: proton affinities, polarizabilities, nucleobase dimer interactions, dimethyl phosphate anion, nucleoside sugar and glycosidic torsion conformations, and RNA phosphoryl transfer model reactions. As an additional baseline, comparisons are made with several commonly used density‐functional models, including M062X and B3LYP (in some cases with dispersion corrections). The results show that, among the semiempirical models examined, the AM1/d‐PhoT model is the most robust at predicting proton affinities. AM1/d‐PhoT and DFTB3‐3ob/OPhyd reproduce the MP2 potential energy surfaces of 6 associative RNA phosphoryl transfer model reactions reasonably well. Further, a recently developed linear‐scaling “modified divide‐and‐conquer” model exhibits the most accurate results for binding energies of both hydrogen bonded and stacked nucleobase dimers. The semiempirical models considered here are shown to underestimate the isotropic polarizabilities of neutral molecules by approximately 30%. The semiempirical models also fail to adequately describe torsion profiles for the dimethyl phosphate anion, the nucleoside sugar ring puckers, and the rotations about the nucleoside glycosidic bond. The modeling of pentavalent phosphorus, particularly with thio substitutions often used experimentally as mechanistic probes, was problematic for all of the models considered. Analysis of the strengths and weakness of the models suggests that the creation of robust next‐generation models should emphasize the improvement of relative conformational energies and barriers, and nonbonded interactions. © 2015 Wiley Periodicals, Inc.     

QM/MM modeling of the hydroxylation of the androstenedione substrate catalyzed by cytochrome P450 aromatase (CYP19A1)

CYP19A1 aromatase is a member of the Cytochrome P450 family of hemeproteins, and is the enzyme responsible for the final step of the androgens conversion into the corresponding estrogens, via a three‐step oxidative process. For this reason, the inhibition of this enzyme plays an important role in the treatment of hormone‐dependent breast cancer. The first catalytic subcycle, corresponding to the hydroxilation of androstenedione, has been proposed to occur through a first hydrogen abstraction and a subsequent oxygen rebound step. In present work, we have studied the mechanism of the first catalytic subcycle by means of hybrid quantum mechanics/molecular mechanics methods. The inclusion of the protein flexibility has been achieved by means of Free Energy Perturbation techniques, giving rise to a free energy of activation for the hydrogen abstraction step of 13.5 kcal/mol. The subsequent oxygen rebound step, characterized by a small free energy barrier (1.5 kcal/mol), leads to the hydroxylated products through a highly exergonic reaction. In addition, an analysis of the primary deuterium kinetic isotopic effects, calculated for the hydrogen abstraction step, reveals values (～10) overpassing the semiclassical limit for the C? H, indicating the presence of a substantial tunnel effect. Finally, a decomposition analysis of the interaction energy for the substrate and cofactor in the active site is also discussed. According to our results, the role of the enzymatic environment consists of a transition state stabilization by means of dispersive and polarization effects. © 2015 Wiley Periodicals, Inc.     

The structures and electronic absorption spectra of substituted phenyldiacetylenes: experimental and theoretical studies

The results of experimental and theoretical investigation of the electronic absorption spectra of substituted phenyldiacethylenes are presented. The bands in the experimental spectra were assigned in detail using quantum chemical calculations of the electronic structures and spectra of the molecules. The influence of the interaction of the substituents on the spectral parameters of the systems under study was analyzed. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1947–1953, October, 2007.     

一种含噻吩环酰腙及其Cu(Ⅱ)配合物的合成、晶体结构和抗氧化活性及量化计算

合成了一种酰腙类含硫Schiff碱4-(二乙胺基)水杨醛缩2-噻吩甲酰腙一水合物(H₂L·H₂O,1),采用扩散法制备了它的铜配合物[Cu(phen)L](2,phen=菲咯啉),通过元素分析、红外光谱、紫外光谱和X射线单晶衍射对它们进行了表征。1的晶体属正交晶系,P2₁2₁2空间群;2的晶体属单斜晶系,P2₁/c空间群。在2中H₂L以烯醇式脱除羟基质子与铜配位,中心离子的配位环境为畸变的四方锥构型。应用Gaussian 09程序,采用密度泛函方法(DFT),分别在B3LYP/6-31G(d)和UB3LYP/6-31G(d)水平对1和2进行了量化计算,对分子的前线分子轨道的能量和组成以及电子光谱进行了分析讨论。测试、分析了化合物的抗氧化活性。     

Highly photoluminescent MoOx quantum dots: Facile synthesis and application in off-on Pi sensing in lake water samples

Molybdenum oxide (MoO_x) is a well-studied transition-metal semiconductor material, and has a wider band gap than MoS₂ which makes it become a promising versatile probe in a variety of fields, such as gas sensor, catalysis, energy storage ect. However, few MoO_x nanomaterials possessing photoluminescence have been reported until now, not to mention the application as photoluminescent probes. Herein, a one-pot method is developed for facile synthesis of highly photoluminescent MoO_x quantum dots (MoO_x QDs) in which commercial molybdenum disulfide powder and hydrogen peroxide (H₂O₂) are involved as the precursor and oxidant, respectively. Compared with current synthesis methods, the proposed one has the advantages of rapid, one-pot, easily prepared, environment friendly as well as strong photoluminescence. The obtained MoO_x QDs is further utilized as an efficient photoluminescent probe, and a new off-on sensor has been constructed for phosphate (Pi) determination in complicated lake water samples, attributed to the fact that the binding affinity of Eu³⁺ ions to the oxygen atoms from Pi is much higher than that from the surface of MoO_x QDs. Under the optimal conditions, a good linear relationship was found between the enhanced photoluminescence intensity and Pi concentration in the range of 0.1–160.0 μM with the detection limit of 56 nM (3σ/k). The first application of the photoluminescent MoO_x nanomaterials for ion photochemical sensing will open the gate of employing MoO_x nanomaterials as versatile probes in a variety of fields, such as chemi-/bio-sensor, cell imaging, biomedical and so on.     

CdSe quantum dots in chiral smectic C matrix: experimental evidence of smectic layer distortion by small and wide angle X-ray scattering and subsequent effect on electro-optical parameters

CdSe quantum dots (QDs) dispersed ferroelectric liquid crystal (FLC) has been subjected to small and wide-angle X-ray scattering and atomic force microscopy to understand the molecular organization in chiral smectic C (SmC*) phase. SAXS indicates that the presence of QDs causes enhancement in the smectic layer separation. The smectic order parameter for neat FLC and FLC–QDs mixtures is obtained in the range of 0.6 to 0.85. Both smectic order parameter and structural tilt are found to be lesser for FLC–QDs mixtures as compared to neat FLC. The insertion of QDs in SmC* matrix causes localized smectic layer distortion in such a way that spontaneous polarization remains almost the same but the electro-optic switching of molecules becomes faster. We have outlined the superiority of FLC–QDs mixtures for electrical energy storage and their suitability in electronic devices.     

Identification of decomposition reactions for HMDSO organosilicon using quantum chemical calculations

Hexamethyldisiloxane [HMDSO, (CH₃)₃-SiOSi-(CH₃)₃] is an important precursor for SiO₂ formation during flame-based silica material synthesis. As a result, HMDSO reactions in flame have been widely investigated experimentally, and many results have indicated that HMDSO decomposition reactions occur very early in this process. In this paper, quantum chemical calculations are performed to identify the initial decomposition of HMDSO and its subsequent reactions using the density functional theory at the level of B3LYP/6-311+G (d, p). Four reaction pathways—(a) Si O bond dissociation of HMDSO, (b) Si C bond dissociation of HMDSO, (c) dissociation and recombination of Si O and Si C bonds, and (d) elimination of a methane molecule from HMDSO—have been examined and identified. From the results, it is found that the barrier of 84.38 kcal/mol and Si O bond dissociation energy of 21.55 kcal/mol are required for the initial decomposition reaction of HMDSO in the first pathway, but the highest free energy barrier (100.69 kcal/mol) is found in the third reaction pathway. By comparing the free energy barriers and reaction rate constants, it is concluded that the most possible initial decomposition reaction of HMDSO is to eliminate the CH₃ radical by Si C bond dissociation.     

痂囊腔菌素A的结构

对实验室生物合成方法制得的痂囊腔菌素A做X射线晶体衍射测定,与文献对照,所属品系及空间群相同,晶胞参数接近,但发现北醌母体外的侧基构型有明显差异,主要表现在两个手性碳原子是R-R型而非S-S型,分别以衍射数据和分子力学优化数据为起始结构,进行STO-3G水平上的结构全优化。计算结果表明所制得的痂囊腔菌素A是一种新的光学活性对映体,由此推测痂囊腔菌素A的高光敏活性可能与手性结构特征有关。     

Adiabatic Potential Energy Surface of the 1,2,3-Trifluorobenzene Cation-Radical

Ab initio study of the adiabatic potential energy surface (PES) for 1,2,3-trifluorobenzene cation-radical was carried out by the ROHF, UHF, MCSCF, MP2, and DFT (B3LYP) methods with the 6-31G* basis set. The PES in question is a pseudorotation surface at all calculation levels. The pseudorotation barrier height does not exceed 3.2 kcal/mol, suggesting a possibility for its manifestations in experimental EPR spectra.     

A benchmark quantum Monte Carlo study of the ground state chromium dimer

We report calculations of the ground state energy and binding curve of the chromium dimer using the variational and diffusion quantum Monte Carlo (VMC and DMC) methods. We examined various single‐determinant and multideterminant wavefunctions multiplied by a Jastrow factor as a trial/guiding wavefunction for VMC/DMC. The molecular orbitals in the single determinants were calculated using restricted or unrestricted Hartree–Fock or density functional theory (DFT) calculations where five commonly used local (SVWN5), semilocal (PW91 and BLYP), and hybrid (B1LYP and B3LYP) functionals were examined. The multideterminant expansions were obtained from the generalized valence bond and (truncated) unrestricted configuration interaction with single and double excitations (UCISD) methods. We also examined a UCISD wavefunction in which UCISD expansions were added to the UB3LYP single‐determinant reference, and their coefficients were optimized at the VMC level. In addition to the wavefunction dependence, the effects of pseudopotentials and backflow transformation were also investigated. The UB3LYP single‐determinant and multideterminant wavefunctions were found to give the variationally best DMC energies within the framework of single‐determinant and multideterminants, respectively, though both the DMC energies were higher than twice the DMC atomic energy. Some of the VMC binding curves show a flat or quite shallow well bottom, which gets recovered deeper by DMC. All the DMC binding curves have a minimum indicating a bound state, but the unrestricted ones overestimate the equilibrium bond length. © 2011 Wiley Periodicals, Inc. Int J Quantum Chem, 2012