Chloronaphthalenes （PCNs, polychlorinated naphthalenes） are a group of persistent environmental pollutants. In the present study, geometrical optimization and electrostatic potential calculations have been performed...Chloronaphthalenes （PCNs, polychlorinated naphthalenes） are a group of persistent environmental pollutants. In the present study, geometrical optimization and electrostatic potential calculations have been performed for all 75 PCNs at the HF/6-31G^＊ level of theory. A number of statistic based parameters have been extracted. Linear relationships between gas-chromatographic retention index （RI） of 62 PCNs in a non-polar column （DB-5） and the structural descriptors have been established by stepwise multiple regression technique. The result shows that two quantities derived from electrostatic potential on molecular surface, ∑Vs- and σ＋^2, together with the number of chlorine （ NCl ） and the energy of the highest occupied molecular orbital （EHOMO） can be well used to express the quantitative structure-retention relationship （QSRR） of PCNs. Predictive capability of the model has been demonstrated by leave-one-out cross-validation with the cross-validated correlation coefficient （Rcv^2） of 0.997, and further compared with the results from similar researches published recently. Furthermore, when splitting the 62 PCNs into training and validation sets in the ratio of 2：1, a similar treatment yields an equation of almost equal statistical quality and very similar regression coefficients, validating the robustness and prediction capability of our model. The QSRR model established may provide a new powerful method for predicting chromatographic properties of polychlorinated naphthalenes.展开更多
In this research, the hydrogen bonds Y···H-X （X = C, N; Y = N, O） of thymine and uracil have been theoretically studied. The results show that hydrogen bond leads to bond length elongation and stretch...In this research, the hydrogen bonds Y···H-X （X = C, N; Y = N, O） of thymine and uracil have been theoretically studied. The results show that hydrogen bond leads to bond length elongation and stretches the frequency red-shift of N-H···Y. Meanwhile, the C-H···O bonds shorten and stretch the frequency blue-shift. They all belong to traditional hydrogen bonds. The intermolecular charge transfer caused by the intermolecular hyperconjugation s＊（N–H） → n（Y） and intramolecular charge redistribution by intramolecular hyperconjugation σ（C-H） →σ＊（C-N） play important roles in the formation of hydrogen bonds. According to thejudgment standards proposed by Bader and Popelier, these hydrogen bonds have typical electron density topological properties. Electrostatic surface potential （ESP） is a useful physicochemical property of a molecule that provides insights into inter- and intramolecular associations, as well as the prediction of likely sites of electrophilic and nucleophilic metabolic attack.展开更多
Rhein(Rhe), an anthraquinone derivative, exhibits excellent anti-inflammatory effects and other pharmacological activities, but its clinical application remains limited due to poor solubility. The present work aims at...Rhein(Rhe), an anthraquinone derivative, exhibits excellent anti-inflammatory effects and other pharmacological activities, but its clinical application remains limited due to poor solubility. The present work aims at the improvement of solubility and oral bioavailability of Rhe through cocrystal formation. For this purpose, Rhe and matrine(Mat) were selected as pharmaceutical ingredient(API) and cocrystal former(CCF), respectively, and the Rhe-Mat cocrystal was synthesized and characterized by single crystal X-ray diffraction(SXRD), powder X-ray diffraction(PXRD), thermogravimetric analysis(TGA), differential scanning calorimetry(DSC). The formation mechanism of Rhe-Mat cocrystal was elucidated by molecular surface electrostatic potential(MSEP). It is worth mentioning that the 50-fold increment of dissolution in vitro was observed in pure water in the form of Rhe-Mat cocrystal. Furthermore, the in vivo studies revealed that Rhe-Mat cocrystal indicated the faster absorption rate and the higher peak blood concentration than the pure Rhe. Hence, it can be concluded that current study successfully improved the solubility and oral bioavailability of Rhe.展开更多
Targeted-delivery is of great importance to molecular probes and drugs for cell biology study. Herein we reported 11 sulfur-containing coumarins as cell imaging probes. Different sulfur speciation of the 4 representat...Targeted-delivery is of great importance to molecular probes and drugs for cell biology study. Herein we reported 11 sulfur-containing coumarins as cell imaging probes. Different sulfur speciation of the 4 representative coumarins SC1-SC4 renders them significantly different subcellular localizations and cellular uptake pathways： SC1 containing thioether group located in lysosomes, while sulfoxide and sulfone compounds SC2 and SC3 distributed in the whole cell. Furthermore, the cationic sulfonium containing compound SC4 was internalized by clathrin-mediated endocytosis and localized at mitochondria. By analyzing the molecular parameters of all 11 coumarins, we found that different sulfur speciation affected their lipophilicity and electrostatic surface potential. These two key factors play roles in altering biological behaviors of the coumarins. The results revealed the importance of sulfur speciation on the physicochemical properties and thus subcellular localization of bioprobes. This is useful for designing new functional bioprobes.展开更多
基金Supported by the Analysis and Measurement Planning Project of Zhejiang Province (2007F70053)
文摘Chloronaphthalenes （PCNs, polychlorinated naphthalenes） are a group of persistent environmental pollutants. In the present study, geometrical optimization and electrostatic potential calculations have been performed for all 75 PCNs at the HF/6-31G^＊ level of theory. A number of statistic based parameters have been extracted. Linear relationships between gas-chromatographic retention index （RI） of 62 PCNs in a non-polar column （DB-5） and the structural descriptors have been established by stepwise multiple regression technique. The result shows that two quantities derived from electrostatic potential on molecular surface, ∑Vs- and σ＋^2, together with the number of chlorine （ NCl ） and the energy of the highest occupied molecular orbital （EHOMO） can be well used to express the quantitative structure-retention relationship （QSRR） of PCNs. Predictive capability of the model has been demonstrated by leave-one-out cross-validation with the cross-validated correlation coefficient （Rcv^2） of 0.997, and further compared with the results from similar researches published recently. Furthermore, when splitting the 62 PCNs into training and validation sets in the ratio of 2：1, a similar treatment yields an equation of almost equal statistical quality and very similar regression coefficients, validating the robustness and prediction capability of our model. The QSRR model established may provide a new powerful method for predicting chromatographic properties of polychlorinated naphthalenes.
基金Supported by the National Natural Science Foundation of China(20873103)
文摘In this research, the hydrogen bonds Y···H-X （X = C, N; Y = N, O） of thymine and uracil have been theoretically studied. The results show that hydrogen bond leads to bond length elongation and stretches the frequency red-shift of N-H···Y. Meanwhile, the C-H···O bonds shorten and stretch the frequency blue-shift. They all belong to traditional hydrogen bonds. The intermolecular charge transfer caused by the intermolecular hyperconjugation s＊（N–H） → n（Y） and intramolecular charge redistribution by intramolecular hyperconjugation σ（C-H） →σ＊（C-N） play important roles in the formation of hydrogen bonds. According to thejudgment standards proposed by Bader and Popelier, these hydrogen bonds have typical electron density topological properties. Electrostatic surface potential （ESP） is a useful physicochemical property of a molecule that provides insights into inter- and intramolecular associations, as well as the prediction of likely sites of electrophilic and nucleophilic metabolic attack.
基金supported by Drug Innovation Major Project (Nos. 2018ZX09711001–001–015, 2018ZX09711001–003– 022)CAMS Innovation Fund for Medical Sciences (No. 2016I2M-3–007)。
文摘Rhein(Rhe), an anthraquinone derivative, exhibits excellent anti-inflammatory effects and other pharmacological activities, but its clinical application remains limited due to poor solubility. The present work aims at the improvement of solubility and oral bioavailability of Rhe through cocrystal formation. For this purpose, Rhe and matrine(Mat) were selected as pharmaceutical ingredient(API) and cocrystal former(CCF), respectively, and the Rhe-Mat cocrystal was synthesized and characterized by single crystal X-ray diffraction(SXRD), powder X-ray diffraction(PXRD), thermogravimetric analysis(TGA), differential scanning calorimetry(DSC). The formation mechanism of Rhe-Mat cocrystal was elucidated by molecular surface electrostatic potential(MSEP). It is worth mentioning that the 50-fold increment of dissolution in vitro was observed in pure water in the form of Rhe-Mat cocrystal. Furthermore, the in vivo studies revealed that Rhe-Mat cocrystal indicated the faster absorption rate and the higher peak blood concentration than the pure Rhe. Hence, it can be concluded that current study successfully improved the solubility and oral bioavailability of Rhe.
基金financial support from the National Key Basic Research Support Foundation of China(No. 2015CB856301)the National Natural Scientific Foundation of China (Nos. 21571007, 21271013,21321001)
文摘Targeted-delivery is of great importance to molecular probes and drugs for cell biology study. Herein we reported 11 sulfur-containing coumarins as cell imaging probes. Different sulfur speciation of the 4 representative coumarins SC1-SC4 renders them significantly different subcellular localizations and cellular uptake pathways： SC1 containing thioether group located in lysosomes, while sulfoxide and sulfone compounds SC2 and SC3 distributed in the whole cell. Furthermore, the cationic sulfonium containing compound SC4 was internalized by clathrin-mediated endocytosis and localized at mitochondria. By analyzing the molecular parameters of all 11 coumarins, we found that different sulfur speciation affected their lipophilicity and electrostatic surface potential. These two key factors play roles in altering biological behaviors of the coumarins. The results revealed the importance of sulfur speciation on the physicochemical properties and thus subcellular localization of bioprobes. This is useful for designing new functional bioprobes.
