Theoretical 14N nuclear quadrupole resonance parameters for sulfa drugs: sulfamerazine and sulfathiazole

A density functional theory investigation was carried out to characterize (14)N electric field gradient tensors, EFG, in crystalline sulfamerazine and sulfathiazole. To include hydrogen-bonding effects in the calculations, the most probable interacting molecules with the target were considered as tetrameric and pentameric clusters, respectively. The calculated EFG tensors were used to evaluate nuclear quadrupole coupling tensors (chi(ii)) and asymmetry parameters (eta(Q)) for the target molecule in the clusters. Results are in satisfactory agreement with the experimental data. The EFG calculations reveal different contributions of nitrogen atoms in hydrogen-bonding network of the sulfamerazine and sulfathiazole. Moreover, based on the results obtained via atoms in molecules (AIM) analyses, an acceptable linear relation between (14)N nuclear quadrupole coupling constants and charge density values at N-H...N and N-H...O bond critical points, rho(b)(r(cp)), is observed.     

A theoretical study on the characteristics of the intermolecular interactions in the active site of human androsterone sulphotransferase: DFT calculations of NQR and NMR parameters and QTAIM analysis

A theoretical study at the level of density functional theory (DFT) was performed to characterize noncovalent intermolecular interactions, especially hydrogen bond interactions, in the active site of enzyme human androsterone sulphotransferase (SULT2A1/ADT). Geometry optimization, interaction energy, ²H, ¹⁴N, and ¹⁷O electric field gradient (EFG) tensors, ¹H, ¹³C, ¹⁷O, and ¹⁵N chemical shielding (CS) tensors, Natural Bonding Orbital (NBO) analysis, and quantum theory of atoms in molecules (QTAIM) analysis of this active site were investigated. It was found that androsterone (ADT) is able to form hydrogen bonds with residues Ser80, Ile82, and His99 of the active site. The interaction energy calculations and NBO analysis revealed that the ADT molecule forms the strongest hydrogen bond with Ser80. Results revealed that ADT interacts with the other residues through electrostatic and Van der Waals interactions. Results showed that these hydrogen bonds influence on the calculated ²H, ¹⁴N, and ¹⁷O quadrupole coupling constants (QCCs), as well as ¹H, ¹³C, ¹⁷O, and ¹⁵N CS tensors. The magnitude of the QCC and CS changes at each nucleus depends directly on its amount of contribution to the hydrogen bond interaction.     

量子化学计算苄嘧磺隆的晶体结构

制备苄嘧磺隆的单晶并用X射线衍射测定晶体结构。苄嘧磺隆晶体属于单斜晶系,C2/c空间群。晶胞参数为:a=33.831(7),b=6.902 0(14),c=16.021(3),α=90.00(3)。,β=104.48(3)。,γ=90.00(3)°,V=3 622.1(13)~3。晶体分子内通过N-H…N氢键和C-H…0氢键形成2个六元环,使分子结构较稳定。苯环平面和嘧啶环平面之间的夹角为50.00(15)°。晶体以1中心对称二聚体为基本重复单元。2个分子间以N-H…O氢键和C-H…O氢键连接。晶体由这些二聚体以范德华作用力堆积而成。使用Gaussian 03程序,用B3LYP/6-31G(d,p)法计算分子的优化结构、电荷分布、稳定性、前沿轨道布居分析和3D示意图。算得分子的键长键角数据和X射线衍射的晶体结构数据基本相符。键长和键角的计算值与X射线衍射数据之差证实晶体中分子间的氢键。     

Theoretical hydrogen bonding parameters for drug design.

Hydrogen bonding interactions play a major role in many chemical and biological processes. This article describes the development of a method for the quantitative estimation of the hydrogen-bonding donor strengths of OH/NH moieties and of the hydrogen bonding acceptor strengths of O/N atoms in different chemical structures. The method is based on the correlation of experimentally observed hydrogen-bonding strengths with quantum-mechanical derived properties, calculated on the acceptor atom (for hydrogen-bond acceptors) and on the heavy atom attached to the donor hydrogen (for hydrogen-bond donors). The properties giving the best correlation with the experimental hydrogen bonding scales were electrophilic superdelocalizability and self-atom polarizability. The best equations found have been implemented in a Web-based tool for hydrogen-bond strength prediction.     

Interaction of Ia and IIa group cations with the guanine site in cytosine-guanine nucleic acid base pair: an ab initio Hartree Fock study in the absence of basis set superposition error

Structures and energetics of complexes between guanine...cytosine Watson Crick (GCWC) DNA base pair and various metal cations were investigated by an ab initio Hartree Fock (HF) study in the absence of basis set superposition error. Cations were allowed to interact with N7 and O6 sites of guanine. The BSSE free gradient geometry optimisation were performed in the framework of the SCF-MI (self consistent field for molecular interactions) theory. In particular, the structure of the complex with the mono and bivalent cations, like H+, Na+, K+, Mg++, Ca++ were analysed showing that the coordination to the N7 and O6 sites of the GCWC pair can generate non-WC hydrogen bonding patterns. The results demonstrate that the a priori elimination of the BSSE allows to study molecular clusters of biological interest by employing small basis sets.     

First-principles study of hydrogen diffusion mechanism in Cr_2O_3

The system energy of H atom occupying different positions in Cr2O3 crystal lattice is calculated by adopting the first-principles calculation method based on density functional theory in this paper. The results indicate that the most stable position of H atom in Cr2O3 crystal lattice locates at the bilateral positions of the center of the unoccupied O octahedral interstice. The reason resulting in this situation is analyzed by comparing the change of Cr2O3 lattice distortion and density of states in Cr2O3_H...     

二氧化碳水合物小晶穴和大晶穴的密度泛函研究

本文通过B3LYP方法,在6-31G(d,p)水平下对结构Ⅰ型二氧化碳水合物的十二面体小晶穴和十四面体大晶穴的结构进行优化,并计算了其振动频率.13C-NMR化学屏蔽常数及电子密度.结果表明,水合物晶穴的氢键键能强于水分子二聚体和冰晶格中的氢键键能.由此可以看出结构Ⅰ型二氧化碳水合物的晶穴是由氢键组成的稳定结构.通过CO2分子与大、小晶穴的范德华能比较,发现C02分子在大晶穴中更稳定.所计算出的C=O键的不对称伸缩振动频率和13C-NMR化学屏蔽常数与文献中的实验值基本一致.通过分析CO2与晶穴的电子密度,其结果与氢键键能计算结果一致,计算结果还表明,CO2在大晶穴中的稳定性较在小晶穴中的稳定性强.     

基于多元线性回归及支持向量机回归分析对含苯基的羧酸类化合物pKa的预测

本文建立了2个180个含苯基的羧酸类化合物酸碱解离常数(pKa)的定量预测模型。这些化合物分子量在122.12到288.34的范围内,包含H,C,N,O,S,F,Cl,Br及I等元素.使用Cerius~2程序计算236个分子描述符来表述这些化合物,并使用统计学方法从中选择了12个描述符.分别使用多元线性回归分析(MLR)及支持向量机回归(SVM)结合10重交互检验方法来预测pKa数值.多元线性回归模型对pKa的预测结果相关系数为0.90,标准偏差为0.32;支持向量机模型结果较好,相关系数为0.91,标准偏差为0.31.     

A large scale molecular dynamics simulation code using the fast multipole algorithm (FMD): performance and application

We present the performance of the fast classical molecular dynamics (MD) code, fast molecular dynamics (FMD), designed for efficient, object-oriented, and scalable large scale simulations, and summarize its application to a liquid crystalline cluster. FMD uses an implementation of the three-dimensional fast multipole method, developed in our group. The fast multipole method offers an efficient way (order O(N)) to handle long range electrostatic interactions, thus, enabling more realistic simulations of large molecular systems. Performance testing was carried out on IBM SP2, SGI Origin 2000, and CRAY T3E massively parallel systems using the MPI massage passing library. The electrostatic forces were tested on models of up to 100,000 randomly placed charges, and on protein and liquid crystalline molecular systems of over 99,000 atoms. Tests on the stability of the method are presented, along with comparisons with direct calculations, the NAMD2 code, and the physical multipole-based cell-multipole method.     

A theoretical survey of substituent effects on the properties of pnicogen and hydrogen bonds in cationic complexes of PH4+ with substituted benzonitrile

In this paper, we analyze the substituent effects on the nature and characteristics of P⋯N and H⋯N interactions in X-PhCN:PH₄⁺ complexes (X = H, F, Cl, Br, CN, NH₂, NO₂, CH₃ and N(CH₃)₂) as a working model at MP2(FC)/6-311++G(d,p) level of theory. The natural bond orbital (NBO) method as well as the quantum theory of atoms in molecules (AIM) is applied to characterize interactions in the studied complexes. In general, the pnicogen bonded systems are more stable than the corresponding hydrogen bonded cases. The strength of the interactions generally correlates well with the magnitudes of the negative electrostatic potentials of the nitrogen atom of isolated substituted benzonitrile (V_s,min(N)). The results indicate that increase in the electron withdrawing power of substituents is accompanied by decrease in the absolute value of V_s,min(N). Also, there are meaningful relationships between V_s,min(N) values and the results of AIM and NBO analyses in studied systems. Moreover, it is found that substituent effects on characteristics of P⋯N pnicogen and H⋯N hydrogen bonds can be expressed by Hammett constants.     

炉内再燃区自由基变化及其化学机理的模拟

采用GRI3．0数据库和Gear算法再现炉内再燃脱硝再燃区中化学反应和自由基的变化规律，然后采用敏感性分析的方法揭示再燃区中对NO脱除起直接作用的反应与化学机理。研究表明在再燃脱硝再燃区中直接起到脱硝作用的主要基元物质为：NH、CH3、CH2、CH、HCCO、NCO、C、CH3(S)。HCN和HNCO虽然没有直接和NO反应，但在脱硝中发生重要作用，主要通过形成一些中间自由基发生作用。该研究为再燃脱硝的技术的应用提供理论基础。     

碳,氢,氧,氮物系的焓值与燃烧温度

根据函数关系设计出一种表格,任何只含C,H,O,N 4种元素的可燃物质在标准大气压下与氧,空气或者任意比例的氧,氮混合物或化合物按化学计量比进行绝热燃烧时达到的温度都可精确地查得.本表还可用于非绝热燃烧过程的计算.     

Monte Carlo simulations of I2- (CO2)16 and I2- (N2O)16 clusters. Minimum energy structures and solvation energy

Structures of the I2- (CO2)16 and I2- (N2O)16 clusters have been studied along the dissociation path of the halide ion. Minimum energy structures and solvation energies have been estimated. The influence of the electrostatic interaction on the I2- charge distribution and the structure of the solvation shell has been discussed. It has been shown that the small dipole moment of the N2O molecule does not have much influence on the cluster properties, and the large quadrupole moments of both solvent clusters give the major contribution into electrostatic interactions. The structure of the clusters is more sensitive to different potential models than to the dipole moment of the N2O molecule.     

Insight into analysis of interactions of GW9508 to wild-type and H86F and H137F GPR40: a combined QM/MM study and pharmacophore modeling

GPR40 is a novel potential target for the treatment of type 2 diabetes. In this work, a two-layered ONIOM based QM/MM approach was employed to study the interactions between GW9508 and GPR40: wild-type, H86F, and H137F mutated systems. The calculated results clearly indicated that His137 is directly involved in ligand recognition through the NH-π interaction with the GW9508. In contrast, His86 is not interacting with the GW9508 in the NH-π interaction. The interaction energies, calculated at the MP2/6-31(d, p) level, were performed to gain more insight into the energetic differences of the wild-type and two mutated systems at the atomistic level. In addition, the obtained pharmacophore model was well consistent with structure-functional requirements for the binding of GPR40 agonists and with per-residue energy decomposition of the ONIOM calculations.     

Diffusion of water molecules in crystalline beta-cyclodextrin hydrates

To understand the rapid diffusion mechanism of water molecules in the crystal lattice of hydrated beta-cyclodextrin (beta-CD), molecular dynamics (MD) simulations of crystalline beta-CD were performed at five different relative humidities corresponding to hydration states ranging from beta-CD-9.4H2O to beta-CD-12.3H2O, and in aqueous solution. The trajectories for the crystalline beta-CD hydrates had lengths of 4 ns each, whereas the simulation in aqueous solution extended to 2 ns. Transport of water molecules in the crystal was characterized in terms of a spatially varying diffusion constant and the main direction of diffusion, which were evaluated using newly developed algorithms. The main diffusion pathway winds through the cavities of adjacent doughnut shaped beta-CD molecules and is slightly slanted with respect to the crystallographic b-axis. Water molecules outside the beta-CD cavities have access to the main diffusion pathway. The diffusion constant for transport of water molecules along the main pathway calculated from the MD simulation data adopts 1/30 of the value in bulk water at room temperature. This is in agreement with estimates that can be made from experimental data on the adjustment of a beta-CD crystal to changes in relative humidity.     

Interaction energy analysis on specific binding of influenza virus hemagglutinin to avian and human sialosaccharide receptors: Importance of mutation-induced structural change

On the basis of available molecular structures registered in Protein Data Bank, we have theoretically carried out the interaction energy analysis for the complexes of influenza virus hemagglutinin (HA) proteins and sialosaccharide receptor analogs of host cells. Employing the fragment molecular orbital method for quantum-chemical calculations, the differences in magnitude and pattern of the interactions between the amino acid residues of avian-type (H7N3) or human-type (H7N9) HA and each saccharide part of avian or human receptor were studied in order to elucidate the molecular mechanism of avian-to-human infectious transmission of influenza virus. We have thus confirmed quantitatively that the mutations from the avian HA to the human HA significantly strengthened the binding affinity of human HA to human receptor, while retaining the affinity to avian receptor. In addition to direct effects regarding the changes of interactions between the altered residues and the receptors, we have also found the importance of indirect effects in which structural changes caused by the mutations play vital roles to modify the intermolecular interactions.     

精甲霜灵的电子结构及圆二色谱性质

采用量子化学密度泛函理论在B3LYP/6-311++G**水平上对精甲霜灵分子几何构型进行优化;在优化的基础上进行圆二色谱究。计算结果表明:(1)C(8)=O(9)与N(1)、C(3)=O(4)与O(5)之间均存在p—π共轭,N原子上另外2个取代基分别位于苯环上下方为最稳定构型。(2)VCD谱中,C(10)—H沿C(8)—C(10)—O(11)平面的摇摆振动在1020cm-1处存在正性康登效应;垂直于该平面的摇摆振动在1273cm-1处出现负性康登效应。C(2)原子上的C—H摇摆振动在的1334cm-1处存在强的康登效应。C(3)=O(4)在的1788cm-1处出现较强的吸收峰;C(8)=O(9)由于与手性中心的间隔一个N原子,其在VCD谱中未出现康登效应。(3)甲醇溶液中的理论ECD谱,228nm处存在正性康登效应,与实验值符合较好;同时,理论计算还预测标题化合物在201nm处存在负性康登效应。     

Wave function analysis of MHC-peptide interactions

We have carried out an analysis of the wave function data for three MHC-peptide complexes: HLA-DRbeta1*0101-HA, HLA-DRbeta1*0401-HA and HLA-DRbeta1*0401-Col. We used quantum chemistry computer programs to generate wave function coefficients for these complexes, from which we obtained both molecular and atomic orbital data for both pocket and peptide amino acids within each pocket region. From these discriminated data, interaction molecular orbitals (IMOs) were identified as those with large and similar atomic orbital coefficient contributions from both pocket and peptide amino acids. The present results correlate well with our previous research where only electrostatic moments were used to explore molecular component interactions. Furthermore, we show a quantum chemical methodology to produce more fine-grained results concerning amino acid behavior in the MHC-peptide interaction.     

The equilibrium phase diagram of the pentaerythritol-pentaglycerine-2-amino-2methyl-1,3, propanediol (PE-PG-AMPL) system

Polyalcohols and amines have been considered as potential thermal energy storage materials, owing to their energetic solid-solid phase transitions. In this paper, we present equilibrium phase diagram of Pentaerythritol (PE)–Pentaglycerine (PG)– 2-amino-2methyl-1,3, propanediol (AMPL) ternary system that has been thermodynamically assessed using the CALPHAD method. A special class of, so called, “Plastic Crystals” have tetrahederally configured molecules with O–H⋯O or N–H⋯O layered or chained bonds in the low temperature phase, and store latent heat of transformation during solid-solid phase change in orientationally disordered crystals at higher temperatures. For example, in polyalcohols, there are O–H⋯O bond rotations around the C–C bonds that are responsible for storing large amounts of solid state phase change energy. Several binary equilibrium phase diagrams of polyalcohols, amines and combination thereof have been calculated and experimentally validated. We only know of three ternary phase diagram of these plastic crystals reported, to the best of knowledge. In the thermodynamic calculations of thePE-PG-AMPL system, we used the binary phase diagram experimental data for the optimization and calculation of excess energies. The binary systems have been optimized using regular and sub-regular solution models. The binaries as well as the ternary system have been calculated from room temperature to the liquid phase. The solution phases are modeled as substitutional solutions, in which the excess Gibbs energies are expressed by the Redlich–Kister–Muggianu polynomial. There is a very good agreement between previously reported experimental data and the calculated phase diagrams.