Spectral (FT-IR,NMR) Analyses,Molecular Structures,and Chemical Bonding of Two Hexahydroacridine-1,8(2H,5H)-dione Derivatives: A Comparative Quantum Chemical Study

A comparative study on two hexahydroacridine-1,8(2H,5H)-dione deriv-atives namely, 9,10-bis(4-fluorophenyl)-3,3,6,6-tetramethyl-3,4,-6,7,9,10-hexahy-droacridine-1,8(2H,5H)-dione (FTHD) and 10-(4-fluorophenyl)-3,3,6,6-tetramethyl-9-(3,4,5-trimethoxyphenyl)-3,4,6,-7,9,10-hexahyd-roacridine-1,8(2H,5H)-dione (FTMPHD) has been performed. ¹H and ¹³C NMR spectra have been recorded in the CDCl₃ solvent. The equilibrium geometries of FTHD and FTMPHD have been determined and analyzed at DFT level employing B3PW91/6-311++G (d,p) method. The vibrational spectra of both the molecules are calculated and compared with the experimental FT-IR spectra. ¹H and ¹³C NMR spectra have been calculated by using the gauge-independent atomic orbital (GIAO) method. The calculated spectra have been found to be in good agreement with the experimental spectra. The quantum theory of atoms-in-molecule (QTAIM) approach is employed to study various intramolecular interactions within these molecules. The highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO) and the molecular electrostatic potential (MESP) surfaces have been constructed and analyzed. Various electronic as well as thermodynamic parameters have been reported.     

Quantum‐chemical treatment of the linoleic acid molecule and two of its conjugated isomers

The structural, vibrational and electronic properties of the linoleic acid molecule and two of its conjugated isomers were investigated theoretically by performing the molecular mechanics (MM+ force field), the semi‐empirical self‐consistent‐field molecular‐orbital (PM3), and the density functional theory (B3LYP) calculations. The geometries of the considered molecules were optimized; the vibrational dynamics and the electronic properties were calculated in their ground states in the gas phase. It was found that the excess charge accumulated on hydrogen atoms bonded to double‐bonded carbon atoms is relatively small, which may cause these hydrogen atoms to be easily abstracted.     

A Combination of 3D-QSAR, Molecular Docking and Molecular Dynamics Simulation Studies of Benzimidazole-Quinolinone Derivatives as iNOS Inhibitors

Inducible Nitric Oxide Synthase (iNOS) has been involved in a variety of diseases, and thus it is interesting to discover and optimize new iNOS inhibitors. In previous studies, a series of benzimidazole-quinolinone derivatives with high inhibitory activity against human iNOS were discovered. In this work, three-dimensional quantitative structure-activity relationships (3D-QSAR), molecular docking and molecular dynamics (MD) simulation approaches were applied to investigate the functionalities of active molecular interaction between these active ligands and iNOS. A QSAR model with R² of 0.9356, Q² of 0.8373 and Pearson-R value of 0.9406 was constructed, which presents a good predictive ability in both internal and external validation. Furthermore, a combined analysis incorporating the obtained model and the MD results indicates: (1) compounds with the proper-size hydrophobic substituents at position 3 in ring-C (R₃ substituent), hydrophilic substituents near the X₆ of ring-D and hydrophilic or H-bond acceptor groups at position 2 in ring-B show enhanced biological activities; (2) Met368, Trp366, Gly365, Tyr367, Phe363, Pro344, Gln257, Val346, Asn364, Met349, Thr370, Glu371 and Tyr485 are key amino acids in the active pocket, and activities of iNOS inhibitors are consistent with their capability to alter the position of these important residues, especially Glu371 and Thr370. The results provide a set of useful guidelines for the rational design of novel iNOS inhibitors.     

DFT Study of the Molecular and Electronic Structure of Metal-Free Tetrabenzoporphyrin and Its Metal Complexes with Zn,Cd, Al,Ga, In

The electronic and molecular structures of metal-free tetrabenzoporphyrin (H₂TBP) and its complexes with zinc, cadmium, aluminum, gallium and indium were investigated by density functional theory (DFT) calculations with a def2-TZVP basis set. A geometrical structure of ZnTBP and CdTBP was found to possess D_4h symmetry; AlClTBP, GaClTBP and InClTBP were non-planar complexes with C_4v symmetry. The molecular structure of H₂TBP belonged to the point symmetry group of D_2h. According to the results of the natural bond orbital (NBO) analysis, the M-N bonds had a substantial ionic character in the cases of the Zn(II) and Cd(II) complexes, with a noticeably increased covalent contribution for Al(III), Ga(III) and In(III) complexes with an axial –Cl ligand. The lowest excited states were computed with the use of time-dependent density functional theory (TDDFT) calculations. The model electronic absorption spectra indicated a weak influence of the nature of the metal on the Q-band position.     

Structural Determination of Three Different Series of Compounds as Hsp90 Inhibitors Using 3D-QSAR Modeling, Molecular Docking and Molecular Dynamics Methods

Hsp90 is involved in correcting, folding, maturation and activation of a diverse array of client proteins; it has also been implicated in the treatment of cancer in recent years. In this work, comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA), molecular docking and molecular dynamics were performed on three different series of Hsp90 inhibitors to build 3D-QSAR models, which were based on the ligand-based or receptor-based methods. The optimum 3D-QSAR models exhibited reasonable statistical characteristics with averaging internal q(2) > 0.60 and external r(2) (pred) > 0.66 for Benzamide tetrahydro-4H-carbazol-4-one analogs (BT), AT13387 derivatives (AT) and Dihydroxylphenyl amides (DA). The results revealed that steric effects contributed the most to the BT model, whereas H-bonding was more important to AT, and electrostatic, hydrophobic, H-bond donor almost contributed equally to the DA model. The docking analysis showed that Asp93, Tyr139 and Thr184 in Hsp90 are important for the three series of inhibitors. Molecular dynamics simulation (MD) further indicated that the conformation derived from docking is basically consistent with the average structure extracted from MD simulation. These results not only lead to a better understanding of interactions between these inhibitors and Hsp90 receptor but also provide useful information for the design of new inhibitors with a specific activity.     

Developments in Molecular Recognition and Sensing at Interfaces

In biological systems, molecular recognition events occur mostly within interfacial environments such as at membrane surfaces, enzyme reaction sites, or at the interior of the DNA double helix. Investigation of molecular recognition at model interfaces provides great insights into biological phenomena. Molecular recognition at interfaces not only has relevance to biological systems but is also important for modern applications such as high sensitivity sensors. Selective binding of guest molecules in solution to host molecules located at solid surfaces is crucial for electronic or photonic detection of analyte substances. In response to these demands, molecular recognition at interfaces has been investigated extensively during the past two decades using Langmuir monolayers, self-assembled monolayers, and lipid assemblies as recognition media. In this review, advances of molecular recognition at interfaces are briefly summarized.     

An orbital rule for electron transport in molecules

The transfer of electrons in molecules and solids is an essential process both in biological systems and in electronic devices. Devices that take advantage of the unique electronic properties of a single molecule have attracted much attention, and applications of these devices include molecular wire, molecular memory, and molecular diodes. The so-called Landauer formula with Green's function techniques provides a basis for theoretical calculations of coherent electron transport in metal-molecule-metal junctions. We have developed a chemical way of thinking about electron transport in molecules in terms of frontier orbital theory. The phase and amplitude of the HOMO and LUMO of π-conjugated molecules determine the essential properties of their electron transport. By considering a close relationship between Green's function and the molecular orbital, we derived an orbital rule that would help our chemical understanding of the phenomenon. First, the sign of the product of the orbital coefficients at sites r and s in the HOMO should be different from the sign of the product of the orbital coefficients at sites r and s in the LUMO. Second, sites r and s in which the amplitude of the HOMO and LUMO is large should be connected. The derived rule allows us to predict essential electron transport properties, which significantly depend on the route of connection between a molecule and electrodes. Qualitative analyses of the site-dependent electron transport in naphthalene (as shown in the graphics) demonstrate that connections 1-4, 1-5, 2-3, and 2-6 are symmetry-allowed for electron transmission, while connections 1-8 and 2-7 are symmetry-forbidden. On the basis of orbital interaction analysis, we have extended this rule to metal-molecule-metal junctions of dithiol derivatives in which two gold electrodes have direct contacts with a molecule through two Au-S bonds. Recently we confirmed these theoretical predictions experimentally by using nanofabricated mechanically controllable break junctions to measure the single-molecule conductance of naphthalene dithiol derivatives. The measurement of the symmetry-allowed 1,4-naphthalene dithiol shows a single-molecule conductance that exceeds that of the symmetry-forbidden 2,7-naphthalene dithiol by 2 orders of magnitude. Because the HOMO and LUMO levels and the HOMO-LUMO gaps are similar in the derivatives, the difference in the measured molecular conductances arises from the difference in the phase relationship of the frontier orbitals. Thus, the phase, amplitude, and spatial distribution of the frontier orbitals provide a way to rationally control electron transport properties within and between molecules.     

杂环轮烯类化合物密度泛函理论研究

运用量子化学中的密度泛函和含时密度泛函理论法,计算了四种加共轭环的脱氢苯[15]轮烯衍生物的几何构型、电子结构、前线分子轨道和电子光谱性质。计算结果表明当脱氢苯[15]轮烯分子(M)被杂环取代或增加分子的共轭性,对轮烯的键长和键角等结构参数的影响不大,这与轮烯具有较强的共轭性有关。当母体中的苯环被嘧啶环取代时,最大吸收波长蓝移;当母体中的苯环被萘取代时,最大吸收波长与母体中的苯被吡嗪取代时的最大吸收波长相近。     

黄腐酸结构、构象和聚集过程的分子模拟研究

自然界中广泛存在着的腐植物质(HS)有多种化学反应能力,诸如矿物质的风化、养分的生物有效利用和污染物的迁移等相关的生物地球化学反应能力。腐植物质的反应性取决于其官能团的化学特性与微观结构,同时又受到周围环境及介质组分的影响。为了更好地了解腐植物质在水、土壤中的结构、构象以及聚集过程,文中描述了以伯明翰东北部庙宇(TNB)的样本,按离子或非离子的黄腐酸分子结构建模研究的过程。该理论研究结果和黄腐酸的溶解度(偶极矩)、电子和振动光谱等一些实验研究的结果能很好的吻合。其中水分子的存在对静电有很大的稳定作用,并且随着离子化程度的增加,这种作用变得更强。在真空中,由于氢键和非键力相互作用增加,未离子化的聚集体比单体更稳定。因此,随着黄腐酸分子的离子化,聚集作用将不再发生。在溶液中,黄腐酸的浓度是聚集的关键因素。若当量浓度太低,含有两个黄腐酸的系统就不可能发生聚集,但是随着当量浓度的提高,系统中聚集体的数量也将上升,情况就发生改变。离子态是聚集的另一个关键因素。离子态的黄腐酸分子有着更高的负电荷,而这会增强能量势垒,阻碍由布朗运动引起的黄腐酸分子的相互接近。     

Design,Synthesis, Biological Activity and Molecular Dynamics Studies of Specific Protein Tyrosine Phosphatase 1B Inhibitors over SHP-2

Over expressing in PTPN1 (encoding Protein tyrosine phosphatase 1B, PTP1B), a protein tyrosine phosphatase (PTP) that plays an overall positive role in insulin signaling, is linked to the pathogenesis of diabetes and obesity. The relationship between PTP1B and human diseases exhibits PTP1B as the target to treat these diseases. In this article, small weight molecules of the imidazolidine series were screened from databases and optimized on silicon as the inhibitors of PTP1B based on the steric conformation and electronic configuration of thiazolidinedione (TZD) compounds. The top three candidates were tested using an in vitro biological assay after synthesis. Finally, we report a novel inhibitor, Compound 13, that specifically inhibits PTP1B over the closely related phosphatase Src homology 2 (SH2) domain-containing phosphatase 2 (SHP-2) at 80 μM. Its IC₅₀ values are reported in this paper as well. This compound was further verified by computer analysis for its ability to combine the catalytic domains of PTP1B and SHP-2 by molecular dynamics (MD) simulations.     

Experimental and theoretical investigation of the adsorption behaviour of new triazole derivatives as inhibitors for mild steel corrosion in acid media

Three triazole derivatives (4-chloro-acetophenone-O-1′-(1′,3′,4′-triazolyl)-metheneoxime (CATM), 4-methoxyl-acetophenone-O-1′-(1′,3′,4′-triazolyl)-metheneoxime (MATM) and 4-fluoro-acetophenone-O-1′-(1′,3′,4′-triazolyl)-metheneoxime (FATM)) have been synthesized as new inhibitors for the corrosion of mild steel in acid media. The inhibition efficiencies of these inhibitors were evaluated by means of weight loss and electrochemical techniques such as electrochemical impedance spectroscopy (EIS) and polarization curves. Then the surface morphology was studied by scanning electron microscopy (SEM). The adsorption of triazole derivatives is found to obey Langmuir adsorption isotherm, and the thermodynamic parameters were determined and discussed. The relationship between molecular structure of these compounds and their inhibition efficiency has been investigated by ab initio quantum chemical calculations. The electronic properties such as the highest occupied molecular orbital (HOMO), the lowest unoccupied molecular orbital (LUMO) energy levels, energy gap (LUMO-HOMO), dipole moment and molecular orbital densities were computed.     

Ab initio cluster model comparative study of atomic oxygen and sulfur chemisorption on Pt(1 1 1) surface: relevance to heterogeneous catalysis

Chemisorption of atomic oxygen and sulfur on Pt(1 1 1) has been studied by means of the ab initio cluster model approach. For both adsorbates, we consider chemisorption on the threefold open site of the Pt(1 1 1) surface which is represented by a Pt₂₅ cluster model having 12 atoms in the first layer, six in the second and seven in the third. The ab initio molecular orbital Hartree–Fock method and explicitly correlated wavefunctions are used to obtain a reliable estimate of the interaction energy, vibrational frequency for the normal mode of the adsorbate above the surface, and the equilibrium geometry. The chemisorption bond is analyzed using different theoretical techniques including the constrained space orbital variation, CSOV, method, the analysis of dipole moment curves and the use of projection operators. The influence of electronic correlation effects is analyzed using multireference configuration interaction, MRCI, techniques and also, by using post-Hartree–Fock correlation functionals.     

新型D-π-A结构的分子设计及理论研究

应用D-π-A结构理论设计了一类以吖啶酮衍生物为电子供体的新型化合物,并采用密度泛函理论方法初步研究了这类新型有化合物的前线分子轨道。研究表明:化合物Ⅱ、Ⅲ具有较好的分子内电荷转移现象,且三种化合物的激发态能级均高于TiO2导带的能级(-4.40 eV),这些化合物能够作为太阳能电池中的染料敏化剂。     

Molecular quantum spintronics: supramolecular spin valves based on single-molecule magnets and carbon nanotubes

We built new hybrid devices consisting of chemical vapor deposition (CVD) grown carbon nanotube (CNT) transistors, decorated with TbPc(2) (Pc = phthalocyanine) rare-earth based single-molecule magnets (SMMs). The drafting was achieved by tailoring supramolecular π-π interactions between CNTs and SMMs. The magnetoresistance hysteresis loop measurements revealed steep steps, which we can relate to the magnetization reversal of individual SMMs. Indeed, we established that the electronic transport properties of these devices depend strongly on the relative magnetization orientations of the grafted SMMs. The SMMs are playing the role of localized spin polarizer and analyzer on the CNT electronic conducting channel. As a result, we measured magneto-resistance ratios up to several hundred percent. We used this spin valve effect to confirm the strong uniaxial anisotropy and the superparamagnetic blocking temperature (T(B) ~ 1 K) of isolated TbPc(2) SMMs. For the first time, the strength of exchange interaction between the different SMMs of the molecular spin valve geometry could be determined. Our results introduce a new design for operable molecular spintronic devices using the quantum effects of individual SMMs.     

Development of Urea and Thiourea Kynurenamine Derivatives: Synthesis,Molecular Modeling,and Biological Evaluation as Nitric Oxide Synthase Inhibitors

Herein we describe the synthesis of a new family of kynurenamine derivatives with a urea or thiourea moiety, together with their in vitro biological evaluation as inhibitors of both neuronal and inducible nitric oxide synthases (nNOS and iNOS, respectively), enzymes responsible for the biogenesis of NO. These compounds were synthesized from a 5‐substituted‐2‐nitrophenyl vinyl ketone scaffold in a five‐step procedure with moderate to high chemical yields. In general, the assayed compounds show greater inhibition of iNOS than of nNOS, with 1‐[3‐(2‐amino‐5‐chlorophenyl)‐3‐oxopropyl]‐3‐ethylurea (compound 5 n ) being the most potent iNOS inhibitor in the series and the most iNOS/nNOS‐selective compound. In this regard, we performed molecular modeling studies to propose a binding mode for this family of compounds to both enzymes and, thereby, to elucidate the differential molecular features that could explain the observed selectivity between iNOS and nNOS.     

Pharmacological Classification and Activity Evaluation of Furan and Thiophene Amide Derivatives Applying Semi-Empirical ab initio Molecular Modeling Methods

Pharmacological and physicochemical classification of the furan and thiophene amide derivatives by multiple regression analysis and partial least square (PLS) based on semi-empirical ab initio molecular modeling studies and high-performance liquid chromatography (HPLC) retention data is proposed. Structural parameters obtained from the PCM (Polarizable Continuum Model) method and the literature values of biological activity (antiproliferative for the A431 cells) expressed as LD(50) of the examined furan and thiophene derivatives was used to search for relationships. It was tested how variable molecular modeling conditions considered together, with or without HPLC retention data, allow evaluation of the structural recognition of furan and thiophene derivatives with respect to their pharmacological properties.     

Combined pharmacophore modeling, docking, and 3D-QSAR studies of PLK1 inhibitors

Polo-like kinase 1, an important enzyme with diverse biological actions in cell mitosis, is a promising target for developing novel anticancer drugs. A combined molecular docking, structure-based pharmacophore modeling and three-dimensional quantitative structure-activity relationship (3D-QSAR) study was performed on a set of 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline derivatives as PLK1 inhibitors. The common substructure, molecular docking and pharmacophore-based alignment were used to develop different 3D-QSAR models. The comparative molecular field analysis (CoMFA) and comparative molecule similarity indices analysis (CoMSIA) models gave statistically significant results. These models showed good q(2) and r(2) (pred) values and revealed a good response to test set validation. All of the structural insights obtained from the 3D-QSAR contour maps are consistent with the available crystal structure of PLK1. The contour maps obtained from the 3D-QSAR models in combination with the structure based pharmacophore model help to better interpret the structure-activity relationship. These satisfactory results may aid the design of novel PLK1 inhibitors. This is the first report on 3D-QSAR study of PLK1 inhibitors.     

Combining Molecular Docking and Molecular Dynamics to Predict the Binding Modes of Flavonoid Derivatives with the Neuraminidase of the 2009 H1N1 Influenza A Virus

Control of flavonoid derivatives inhibitors release through the inhibition of neuraminidase has been identified as a potential target for the treatment of H1N1 influenza disease. We have employed molecular dynamics simulation techniques to optimize the 2009 H1N1 influenza neuraminidase X-ray crystal structure. Molecular docking of the compounds revealed the possible binding mode. Our molecular dynamics simulations combined with the solvated interaction energies technique was applied to predict the docking models of the inhibitors in the binding pocket of the H1N1 influenza neuraminidase. In the simulations, the correlation of the predicted and experimental binding free energies of all 20 flavonoid derivatives inhibitors is satisfactory, as indicated by R(2) = 0.75.     

ClCF+的电子结构与光解离通道

用ab initio分子轨道方法对正电子自由基ClCF^ 的电子机构，几何构型，振动频率，过滤态进行量子化学计算，内禀反应坐标法计算结果表明，对于ClCF^ 来说有三条可能的解离通道，从而从理论上验证了在轰击ClCF^ 后所产生的碎片中存在的Cl、CF^ 、F、CCl^ 等粒子。