In this paper, a three-dimensional quantitative structure-activity relationships(3 D-QSAR) study for 20 HIV-1 reverse transcriptase(RT) inhibitors was established using Topomer Co MFA. The models were built based on d...In this paper, a three-dimensional quantitative structure-activity relationships(3 D-QSAR) study for 20 HIV-1 reverse transcriptase(RT) inhibitors was established using Topomer Co MFA. The models were built based on different fragment cutting models, with the most effective model of the multiple correlation coefficients of fitting(r^2) to be 0.920, cross-validation(q^2) of 0.575, and external validation(Q_(ext)~2) being 0.701. The results indicated that the model obtained has both favorable estimation stability and good prediction capability. Topomer Search was used to search R-group from ZINC database. As a result, a series of R-groups with relatively high activity contribution was obtained. By No. 6 molecule filtering, 3 R_1 and 15 R_2 groups were selected, and employed to alternately substitute for the R_1 and R_2 of sample 6. Finally, 45 new compounds were designed, and the Topomer CoMFA model was used to predicate the biological activity, so the Topomer Search is effective in screening and can guide the design of new HIV/AIDS drugs. The molecular docking method was also used to study the interactions of these drugs by docking the ligands into HIV-1 RT active site, which revealed the likely bioactive conformations. This study showed that there are extensive interactions between the 1,3,4-thiazolidinone revertase inhibitors and His84, Asp145, Lys33 and Leu83 residues in the active site of HIV-1 RT. These results provide useful insights for the design of potent new inhibitors of RT.展开更多
With the development of photovoltaic materials, especially the small molecule acceptors(SMAs), organic solar cells(OSCs)have made breakthroughs in power conversion efficiencies(PCEs). However, the stability of high-pe...With the development of photovoltaic materials, especially the small molecule acceptors(SMAs), organic solar cells(OSCs)have made breakthroughs in power conversion efficiencies(PCEs). However, the stability of high-performance OSCs remains a critical challenge for future technological applications. To tackle the inherent instability of SMA materials under the ambient conditions, much effort has been made to improve OSCs stability, including device modification and new materials design. Here we proposed a new electron acceptor design strategy and developed a “quasi-macromolecule”(QM) with an A-π-A structure,where the functionalized π-bridge is used as a linker between two SMAs(A), to improve the long-term stability without deteriorating device efficiencies. Such type of QMs enables excellent synthetic flexibility to modulate their optical/electrochemical properties, crystallization and aggregation behaviors by changing the A and π units. Moreover, QMs possess a unique long conjugated backbone combining high molecular weight over 3.5 k Da with high purity. Compared with the corresponding SMA BTP-4F-OD(Y6-OD), the devices based on newly synthesized A-π-A type acceptors QM1 and QM2 could exhibit better device stability and more promising PCEs of 17.05% and 16.36%, respectively. This kind of “molecular-framework”(A-π-A)structure provides a new design strategy for developing high-efficiency and-stability photovoltaic materials.展开更多
基金supported by the National Natural Science Foundation of China(21475081,21275094)the Graduate Innovation Fund of Shaanxi University of Science and Technology
文摘In this paper, a three-dimensional quantitative structure-activity relationships(3 D-QSAR) study for 20 HIV-1 reverse transcriptase(RT) inhibitors was established using Topomer Co MFA. The models were built based on different fragment cutting models, with the most effective model of the multiple correlation coefficients of fitting(r^2) to be 0.920, cross-validation(q^2) of 0.575, and external validation(Q_(ext)~2) being 0.701. The results indicated that the model obtained has both favorable estimation stability and good prediction capability. Topomer Search was used to search R-group from ZINC database. As a result, a series of R-groups with relatively high activity contribution was obtained. By No. 6 molecule filtering, 3 R_1 and 15 R_2 groups were selected, and employed to alternately substitute for the R_1 and R_2 of sample 6. Finally, 45 new compounds were designed, and the Topomer CoMFA model was used to predicate the biological activity, so the Topomer Search is effective in screening and can guide the design of new HIV/AIDS drugs. The molecular docking method was also used to study the interactions of these drugs by docking the ligands into HIV-1 RT active site, which revealed the likely bioactive conformations. This study showed that there are extensive interactions between the 1,3,4-thiazolidinone revertase inhibitors and His84, Asp145, Lys33 and Leu83 residues in the active site of HIV-1 RT. These results provide useful insights for the design of potent new inhibitors of RT.
基金supported by the National Natural Science Foundation of China (52125306, 21875286, 22005347)the Natural Science Foundation of Hunan Province (2021JJ20068)the National Key Research and Development Program of China (2017YFA0206600)。
文摘With the development of photovoltaic materials, especially the small molecule acceptors(SMAs), organic solar cells(OSCs)have made breakthroughs in power conversion efficiencies(PCEs). However, the stability of high-performance OSCs remains a critical challenge for future technological applications. To tackle the inherent instability of SMA materials under the ambient conditions, much effort has been made to improve OSCs stability, including device modification and new materials design. Here we proposed a new electron acceptor design strategy and developed a “quasi-macromolecule”(QM) with an A-π-A structure,where the functionalized π-bridge is used as a linker between two SMAs(A), to improve the long-term stability without deteriorating device efficiencies. Such type of QMs enables excellent synthetic flexibility to modulate their optical/electrochemical properties, crystallization and aggregation behaviors by changing the A and π units. Moreover, QMs possess a unique long conjugated backbone combining high molecular weight over 3.5 k Da with high purity. Compared with the corresponding SMA BTP-4F-OD(Y6-OD), the devices based on newly synthesized A-π-A type acceptors QM1 and QM2 could exhibit better device stability and more promising PCEs of 17.05% and 16.36%, respectively. This kind of “molecular-framework”(A-π-A)structure provides a new design strategy for developing high-efficiency and-stability photovoltaic materials.
