A molecular electronegativity distance vector(M)based on 13 atomic types has been used to describe the structures of 19 conjugates(LHCc)of levofloxacin-thiadiazole HDAC inhibitor(HDACi)and related inhibitory activitie...A molecular electronegativity distance vector(M)based on 13 atomic types has been used to describe the structures of 19 conjugates(LHCc)of levofloxacin-thiadiazole HDAC inhibitor(HDACi)and related inhibitory activities(pH,i=1,2,6)of LHCc against histone deacetylases(HDACs,such as HDAC1,HDAC2 and HDAC6).The quantitative structure-activity relationships(QSAR)were established by using leaps-and-bounds regression analysis for the inhibitory activities(pH)of 19 above compounds to HDAC1,HDAC2 and HDAC6 along with M.The correlation coefficients(R~2)and the leave-one-out(LOO)cross validation Rfor the pH,pHand pHmodels were 0.976 and 0.949;0.985 and 0.977;0.976 and 0.932,respectively.The QSAR models had favorable correlations,as well as robustness and good prediction capability by R~2,F,R~2,A,Fand Vtests.Validated by using 3876 training sets,the models have good external prediction ability.The results indicate that the molecular structural units:–CH–(g=1,2),–NH,–OH,=O,–O–and–S–are the main factors which can affect the inhibitory activity of pH,pHas well as pHbioactivities of these compounds directly.Accordingly,the main interactions between HDACs inhibitor and HDACs are hydrophobic interaction,hydrogen bond,and coordination with Znto form compounds,which is consistent with the results in reports.展开更多
为验证萜类驱避化合物与嗅觉引诱物二氧化碳存在缔合作用,并研究缔合作用对蚊虫驱避活性的影响。本研究借助计算化学的方法获得缔合体和缔合能量,利用Gaussian View和Gaussian03W软件分别构建和优化二氧化碳、22个萜类蚊虫驱避化合物以...为验证萜类驱避化合物与嗅觉引诱物二氧化碳存在缔合作用,并研究缔合作用对蚊虫驱避活性的影响。本研究借助计算化学的方法获得缔合体和缔合能量,利用Gaussian View和Gaussian03W软件分别构建和优化二氧化碳、22个萜类蚊虫驱避化合物以及它们与二氧化碳缔合后的三维分子结构,经Ampac8.16转化后,获得它们的缔合能量。借助定量构效关系计算方法研究缔合作用对驱避活性的影响,利用Codessa2.7.10计算获得驱避剂和缔合体的各类结构描述符,从包括缔合体结构描述符及特征描述符在内的各类结构参数中筛选显著性参数,以萜类驱避化合物对白纹伊蚊Aedes albopictus的校正驱避率的对数值为活性数据,建立结构描述符与驱避活性的定量构效关系(quantitative structure-activity relationship,QSAR)模型。结果获得了22个萜类驱避化合物与二氧化碳缔合的缔合能量,计算显示它们之间存在缔合作用并且可以形成缔合体;获得1个R2为0.9643的4参数QSAR模型,这4个参数所对应的结构描述符分别是COM-WNSA-3 Weighted PNSA(PNSA3*TMSA/1000)[Zefirov’s PC],f-TerCO2-Min e-n attraction for a C-O bond,M-Max 1-electron reaction index for an Oatom,M-Min(>0.1)bond order of an H atom,前2个参数分别为缔合体的整体结构描述符和碎片特征描述符。计算化学结果表明,萜类驱避化合物与二氧化碳存在缔合作用,该缔合作用对驱避活性的影响显著。展开更多
Quantitative structure-biodegradability relationships （QSBRs） were established to develop predictive models and mechanistic explanations for acid dyestuffs as well as biological activities. With a total of four desc...Quantitative structure-biodegradability relationships （QSBRs） were established to develop predictive models and mechanistic explanations for acid dyestuffs as well as biological activities. With a total of four descriptors, molecular weight （MW）, energies of the highest occupied molecular orbital （EHOMO）, the lowest unoccupied molecular orbital （ELUMO）, and the excited state （EES）, calculated using quantum chemical semi-empirical methodology, a series of models were analyzed between the dye biodegradability and each descriptor. Results showed that EHOMO and Mw were the dominant parameters controlling the biodegradability of acid dyes. A statistically robust QSBR model was developed for all studied dyes, with the combined application of EHOMO and Mw. The calculated biodegradations fitted well with the experimental data monitored in a facultative-aerobic process, indicative of the reliable prediction and mechanistic character of the developed model.展开更多
基金supported by the National Natural Science Foundation of China(21473081,21075138)special fund of State Key Laboratory of Structure Chemistry(20160028)
文摘A molecular electronegativity distance vector(M)based on 13 atomic types has been used to describe the structures of 19 conjugates(LHCc)of levofloxacin-thiadiazole HDAC inhibitor(HDACi)and related inhibitory activities(pH,i=1,2,6)of LHCc against histone deacetylases(HDACs,such as HDAC1,HDAC2 and HDAC6).The quantitative structure-activity relationships(QSAR)were established by using leaps-and-bounds regression analysis for the inhibitory activities(pH)of 19 above compounds to HDAC1,HDAC2 and HDAC6 along with M.The correlation coefficients(R~2)and the leave-one-out(LOO)cross validation Rfor the pH,pHand pHmodels were 0.976 and 0.949;0.985 and 0.977;0.976 and 0.932,respectively.The QSAR models had favorable correlations,as well as robustness and good prediction capability by R~2,F,R~2,A,Fand Vtests.Validated by using 3876 training sets,the models have good external prediction ability.The results indicate that the molecular structural units:–CH–(g=1,2),–NH,–OH,=O,–O–and–S–are the main factors which can affect the inhibitory activity of pH,pHas well as pHbioactivities of these compounds directly.Accordingly,the main interactions between HDACs inhibitor and HDACs are hydrophobic interaction,hydrogen bond,and coordination with Znto form compounds,which is consistent with the results in reports.
文摘为验证萜类驱避化合物与嗅觉引诱物二氧化碳存在缔合作用,并研究缔合作用对蚊虫驱避活性的影响。本研究借助计算化学的方法获得缔合体和缔合能量,利用Gaussian View和Gaussian03W软件分别构建和优化二氧化碳、22个萜类蚊虫驱避化合物以及它们与二氧化碳缔合后的三维分子结构,经Ampac8.16转化后,获得它们的缔合能量。借助定量构效关系计算方法研究缔合作用对驱避活性的影响,利用Codessa2.7.10计算获得驱避剂和缔合体的各类结构描述符,从包括缔合体结构描述符及特征描述符在内的各类结构参数中筛选显著性参数,以萜类驱避化合物对白纹伊蚊Aedes albopictus的校正驱避率的对数值为活性数据,建立结构描述符与驱避活性的定量构效关系(quantitative structure-activity relationship,QSAR)模型。结果获得了22个萜类驱避化合物与二氧化碳缔合的缔合能量,计算显示它们之间存在缔合作用并且可以形成缔合体;获得1个R2为0.9643的4参数QSAR模型,这4个参数所对应的结构描述符分别是COM-WNSA-3 Weighted PNSA(PNSA3*TMSA/1000)[Zefirov’s PC],f-TerCO2-Min e-n attraction for a C-O bond,M-Max 1-electron reaction index for an Oatom,M-Min(>0.1)bond order of an H atom,前2个参数分别为缔合体的整体结构描述符和碎片特征描述符。计算化学结果表明,萜类驱避化合物与二氧化碳存在缔合作用,该缔合作用对驱避活性的影响显著。
基金Project supported by the Natural Science Foundation of Shanghai, China(No. 06ZR14002).
文摘Quantitative structure-biodegradability relationships （QSBRs） were established to develop predictive models and mechanistic explanations for acid dyestuffs as well as biological activities. With a total of four descriptors, molecular weight （MW）, energies of the highest occupied molecular orbital （EHOMO）, the lowest unoccupied molecular orbital （ELUMO）, and the excited state （EES）, calculated using quantum chemical semi-empirical methodology, a series of models were analyzed between the dye biodegradability and each descriptor. Results showed that EHOMO and Mw were the dominant parameters controlling the biodegradability of acid dyes. A statistically robust QSBR model was developed for all studied dyes, with the combined application of EHOMO and Mw. The calculated biodegradations fitted well with the experimental data monitored in a facultative-aerobic process, indicative of the reliable prediction and mechanistic character of the developed model.
