Study on the structure–activity of dihydromyricetin and its new production

Myricetin (MY) was firstly synthesized from dihydromyricetin (DMY), and its antioxidant activity was analyzed. FTIR, NMR, and TG measurements confirmed that the DMY turned to MY. Scanning electron microscope observation showed that the 2,3-single bond offered great flexibility on the stage of crystallization to form imperfect crystalline regions; hence, DMY tends to form larger columnar crystals than MY. It has been found that the antioxidative efficiency of DMY was superior to MY, based on the measurement of radical scavenging activity by DPPH and the oxidation induction time of PP-antioxidant samples. The 2,3-double bond in MY structure, known as one of the characteristic determinants, was not an important requirement for antioxidant capacity or even negative correlation observed. Such a deduction was further supported by UV–Vis absorption spectra change when the pH was raised to pH 9. It was concluded that the ortho-trihydroxyl group in the B ring provides an antioxidant defense, and the 2,3-single band of C ring provides the structural stability.     

Trainable structure–activity relationship model for virtual screening of CYP3A4 inhibition

A new structure–activity relationship model predicting the probability for a compound to inhibit human cytochrome P450 3A4 has been developed using data for >800 compounds from various literature sources and tested on PubChem screening data. Novel GALAS (Global, Adjusted Locally According to Similarity) modeling methodology has been used, which is a combination of baseline global QSAR model and local similarity based corrections. GALAS modeling method allows forecasting the reliability of prediction thus defining the model applicability domain. For compounds within this domain the statistical results of the final model approach the data consistency between experimental data from literature and PubChem datasets with the overall accuracy of 89%. However, the original model is applicable only for less than a half of PubChem database. Since the similarity correction procedure of GALAS modeling method allows straightforward model training, the possibility to expand the applicability domain has been investigated. Experimental data from PubChem dataset served as an example of in-house high-throughput screening data. The model successfully adapted itself to both data classified using the same and different IC₅₀ threshold compared with the training set. In addition, adjustment of the CYP3A4 inhibition model to compounds with a novel chemical scaffold has been demonstrated. The reported GALAS model is proposed as a useful tool for virtual screening of compounds for possible drug-drug interactions even prior to the actual synthesis.     

Controllable preparation of nanosized TiO_2 thin film and relationship between structure of film and its photocatalytic activity

~~Controllable preparation of nanosized TiO_2 thin film and relationship between structure of film and its photocatalytic activity@魏刚$College of Material Science and Engineering,Beijing University of Chemical Technology! Beijing 100029,China @张元晶$College of Material Science and Engineering,Beijing University of Chemical Technology! Beijing 100029,China @熊蓉春$College of Material Science and Engineering,Beijing University of Chemical Technology! Beijing 100029,China~…     

Quantum chemical investigations on the structure–property relationship of aminopolynitrotriazoles

Density functional theory (DFT) has been employed to study the geometric and electronic structures, band gap, thermodynamic properties, density, and performance properties of a series of polynitrotriazoles at the B3LYP/aug-cc-pVDZ level. The detonation performances were evaluated by the Kamlet–Jacobs semi-empirical equations based on the calculated densities and heats of reaction. It has been found that the model compounds with the predicted densities of 1.8 g/cm³, detonation velocities of 8.8 km/s, and detonation pressures of 35 GPa may be novel potential candidates of high energy density materials. The discrepancies in the performance properties, stabilities or sensitivities among isomers are caused by the relative position of NH₂ and NO₂ groups.     

Antioxidant properties of phenolic Schiff bases: structure–activity relationship and mechanism of action

Phenolic Schiff bases are known for their diverse biological activities and ability to scavenge free radicals. To elucidate (1) the structure–antioxidant activity relationship of a series of thirty synthetic derivatives of 2-methoxybezohydrazide phenolic Schiff bases and (2) to determine the major mechanism involved in free radical scavenging, we used density functional theory calculations (B3P86/6-31+(d,p)) within polarizable continuum model. The results showed the importance of the bond dissociation enthalpies (BDEs) related to the first and second (BDE_d) hydrogen atom transfer (intrinsic parameters) for rationalizing the antioxidant activity. In addition to the number of OH groups, the presence of a bromine substituent plays an interesting role in modulating the antioxidant activity. Theoretical thermodynamic and kinetic studies demonstrated that the free radical scavenging by these Schiff bases mainly proceeds through proton-coupled electron transfer rather than sequential proton loss electron transfer, the latter mechanism being only feasible at relatively high pH.     

The crystal structure of δ-VOPO4 and its relationship to ω-VOPO4

The crystal structure of δ-VOPO₄ was determined from powder X-ray diffraction data in the tetragonal space group P4₂/mbc (No. 135) with a = 9.0547(7) Å and c = 8.6080(8) Å. The structure is found to be closely related to that of ω-VOPO₄, thus disproving two traditional structure hypotheses commonly found in the literature. The structural relationship between the two phases is discussed in the light of a recently observed fast phase transition from ω- to δ-VOPO₄.     

A categorical structure–activity relationship analysis of GPR119 ligands

The categorical structure–activity relationship (cat-SAR) expert system has been successfully used in the analysis of chemical compounds that cause toxicity. Herein we describe the use of this fragment-based approach to model ligands for the G protein-coupled receptor 119 (GPR119). Using compounds that are known GPR119 agonists and compounds that we have confirmed experimentally that are not GPR119 agonists, four distinct cat-SAR models were developed. Using a leave-one-out validation routine, the best GPR119 model had an overall concordance of 99%, a sensitivity of 99%, and a specificity of 100%. Our findings from the in-depth fragment analysis of several known GPR119 agonists were consistent with previously reported GPR119 structure–activity relationship (SAR) analyses. Overall, while our results indicate that we have developed a highly predictive cat-SAR model that can be potentially used to rapidly screen for prospective GPR119 ligands, the applicability domain must be taken into consideration. Moreover, our study demonstrates for the first time that the cat-SAR expert system can be used to model G protein-coupled receptor ligands, many of which are important therapeutic agents.     

Visual exploration of structure–activity relationship using maximum common framework

To help tracking all molecules made in a typical medicinal chemistry project, we have developed an algorithm to generate a maximum common framework (MCF) hierarchy and an interactive tool for its visualization and analysis. By identifying all unique frameworks for a set of molecules and all molecules containing each framework, we were able to simplify the MCF hierarchy build up steps and, as a result, speed up the entire process significantly. By allowing compounds to be assigned to multiple MCFs, users can easily remove bad branching nodes and concentrate on interesting ones. MCF hierarchies provide an effective and intuitive visualization for tracking medicinal chemistry lead optimization projects. We will provide examples to illustrate its usefulness.     

Preparation of PLL-PEG-PLL and its application to DNA encapsulation

With the successful sequencing of Human Genome, it would be possible to cure all diseases by gene ther- apy in the near future. However, one of the major problems in gene therapy is the development of gene vectors. To date, there are two kinds of gene vectors, namely, viral and non-viral gene vectors. Viruses are widely used as vectors in gene therapy, with the trans- fection efficiency being relatively high, but they have the safety problems such as immunogenicity, non- biocompatibility and …     

Development of sample preparation technique to characterize chemical structure of humin by synchrotron-radiation–based X-ray photoelectron spectroscopy

Carbon-binding state of humin (HM, a non-conductive insoluble organo-mineral humic substance) was successfully characterized for the first time by synchrotron-radiation–based X-ray photoelectron spectroscopy (XPS). Four sample preparation techniques—HM on double-sided carbon tape, indium sheet, copper mesh, and in pellet formed from the mixture of HM and copper powder (Cu) at different mixing ratios (1:1, 1:2, and 1:6 v/v)—were compared. The results show that HM samples prepared using the first three methods had significant charge buildup, which made the interpretation of the XPS spectra impossible because of the shifts in the binding energy of C 1s XPS spectra. Pellets of HM:Cu mixture enhanced the electrical conductivity and reduced charge buildup on the sample surface. Pellets prepared with HM:Cu ratio of 1:1 (v/v) provided the minimum charge buildup and high sensitivity with difference in C 1s spectra regardless of the observing position. The C 1s spectra, estimated by the subtraction of the carbon contamination in Cu, showed the resolution of CC (284.0 eV), C C/C H (285.1 eV), C O (286.3 eV), CO (287.3 eV), and OC O (288.3 eV) and three additional peaks of CF (289.3 eV), CF₂ (290.2 eV), and CF₃ (291.4 eV). Soft X-ray absorption spectroscopic (XAS) analysis further proved the existence of fluoride (F 1s) in HM structure. The detection of fluorinated carbon in HM showed a great advancement of XPS compared with other conventional analyses. X-ray with the incident angle of 0° provided the smallest (nearly negligible) energy shift in the C 1s spectra of HM and did not damage the surface of the sample.