Electronic structure calculations have been carried out to study various closely related isomers with propane backbone which form part of our quantum chemical approach to inter and intra-molecular kinetics. The useful...Electronic structure calculations have been carried out to study various closely related isomers with propane backbone which form part of our quantum chemical approach to inter and intra-molecular kinetics. The usefulness of UCA-FUKUI developed by Jesús Sánchez-Márquez to facilitate the theoretical study of chemical reactivity is exploited. All isomers are identified as local minima with single-point calculations on DFT/B3LYP/6-31G(d,p). The increasing order of stability by groups of isomers are group I;propn-2-ol, propan-1-ol, group II;propanone, propanal, group III;Ethylmethanoate, Propanoic acid, Methylethanoate, group IV;N,N-dimethylformamide, propanimino, and propanamide. The trend in reactivity of the various groups of isomers and specific points of nucleophilic and electrophilic attacks are presented. We noticed that most of the properties of these isomers taught at the fundamental levels are proven true theoretically.展开更多
Malaria is a life-threatening disease responsible for half a million death annually, and with nearly half of the world’s population at risk. The rapid drop in observed cases of malaria in the last two decades has bee...Malaria is a life-threatening disease responsible for half a million death annually, and with nearly half of the world’s population at risk. The rapid drop in observed cases of malaria in the last two decades has been due to a combination of preventive and therapeutic remedies. However, the absence of a vaccine, new antimalarial chemotherapies and increased parasitic resistance have led to a plateau of infections and renewed research interest in target human and <em>Plasmodium</em> (the malaria parasite) receptors and new drugs. In this study, the impact of mutation on the affinity on antimalarial drugs with the bifunctional enzyme complex, dihydrofolate reductase (DHFR) is explored. In addition, homology modeling is used to build the three-dimensional models of the enzymes<em> Plasmodium</em> telomerase reverse-transcriptase (<em>pf-TERT</em>) and Plasmodium dihydropteroate synthetase (<em>pf-DHPS</em>) to determine their affinity with antimalarial drugs. The interaction energies and stable complexes formed between these enzymes and antimalarial drugs (chloroquine, artemisinin, primaquine, pyrimethamine, sulfadoxine and pentamidine) were modelled using AutoDock vina. Our data indicate that <em>pf-TERT</em> and <em>pf-DHPS</em> form stable complexes with the antimalarial ligands with affinity ranging from <span style="white-space:nowrap;"><span style="white-space:nowrap;">−</span></span>4.0 to <span style="white-space:nowrap;"><span style="white-space:nowrap;">−</span></span>6.9 kcal/mol. The affinity with crystal structures of DHFR receptors was higher ranging from <span style="white-space:nowrap;"><span style="white-space:nowrap;">−</span></span>6.0 to <span style="white-space:nowrap;"><span style="white-space:nowrap;">−</span></span>10.0 kcal/mol. The affinity to DHFR also decreases with the mutation a confirmation of the source of resistance. The highest affinity interaction for all the receptors modeled is observed with Artemisinin a benchmark antimalarial drug. This can be attributed to the size, shape and dipolar surface of the ligand. The observed complexes are stabilized by strategic active site polar and non-polar contacts.展开更多
A combinatorial method based on the determination of the averaged weight of permutations controlling the chirality/achirality fittingness of 2n substitution sites of the monocyclic cycloalkane allows to obtain general...A combinatorial method based on the determination of the averaged weight of permutations controlling the chirality/achirality fittingness of 2n substitution sites of the monocyclic cycloalkane allows to obtain generalized functional equations for direct enumeration of enantiomers pairs and achiral skeletons of any derivatives of monocyclic cycloalkanes having heteromorphic alkyl substituents with the distinct length k with the empirical formula , wherein at least two alkyl groups??of the distinct size ?each. ?is the number of alkyl radicals ?of the system??verifying the relation . The integer sequences of enantiomer pairs and achiral skeletons are given for substituted derivatives of monocyclic cycloalkane for n = 3, 4 and k = 3, 4, 5. The composite stereoisomerism of this particular compound is also highlighted.展开更多
文摘Electronic structure calculations have been carried out to study various closely related isomers with propane backbone which form part of our quantum chemical approach to inter and intra-molecular kinetics. The usefulness of UCA-FUKUI developed by Jesús Sánchez-Márquez to facilitate the theoretical study of chemical reactivity is exploited. All isomers are identified as local minima with single-point calculations on DFT/B3LYP/6-31G(d,p). The increasing order of stability by groups of isomers are group I;propn-2-ol, propan-1-ol, group II;propanone, propanal, group III;Ethylmethanoate, Propanoic acid, Methylethanoate, group IV;N,N-dimethylformamide, propanimino, and propanamide. The trend in reactivity of the various groups of isomers and specific points of nucleophilic and electrophilic attacks are presented. We noticed that most of the properties of these isomers taught at the fundamental levels are proven true theoretically.
文摘Malaria is a life-threatening disease responsible for half a million death annually, and with nearly half of the world’s population at risk. The rapid drop in observed cases of malaria in the last two decades has been due to a combination of preventive and therapeutic remedies. However, the absence of a vaccine, new antimalarial chemotherapies and increased parasitic resistance have led to a plateau of infections and renewed research interest in target human and <em>Plasmodium</em> (the malaria parasite) receptors and new drugs. In this study, the impact of mutation on the affinity on antimalarial drugs with the bifunctional enzyme complex, dihydrofolate reductase (DHFR) is explored. In addition, homology modeling is used to build the three-dimensional models of the enzymes<em> Plasmodium</em> telomerase reverse-transcriptase (<em>pf-TERT</em>) and Plasmodium dihydropteroate synthetase (<em>pf-DHPS</em>) to determine their affinity with antimalarial drugs. The interaction energies and stable complexes formed between these enzymes and antimalarial drugs (chloroquine, artemisinin, primaquine, pyrimethamine, sulfadoxine and pentamidine) were modelled using AutoDock vina. Our data indicate that <em>pf-TERT</em> and <em>pf-DHPS</em> form stable complexes with the antimalarial ligands with affinity ranging from <span style="white-space:nowrap;"><span style="white-space:nowrap;">−</span></span>4.0 to <span style="white-space:nowrap;"><span style="white-space:nowrap;">−</span></span>6.9 kcal/mol. The affinity with crystal structures of DHFR receptors was higher ranging from <span style="white-space:nowrap;"><span style="white-space:nowrap;">−</span></span>6.0 to <span style="white-space:nowrap;"><span style="white-space:nowrap;">−</span></span>10.0 kcal/mol. The affinity to DHFR also decreases with the mutation a confirmation of the source of resistance. The highest affinity interaction for all the receptors modeled is observed with Artemisinin a benchmark antimalarial drug. This can be attributed to the size, shape and dipolar surface of the ligand. The observed complexes are stabilized by strategic active site polar and non-polar contacts.
文摘A combinatorial method based on the determination of the averaged weight of permutations controlling the chirality/achirality fittingness of 2n substitution sites of the monocyclic cycloalkane allows to obtain generalized functional equations for direct enumeration of enantiomers pairs and achiral skeletons of any derivatives of monocyclic cycloalkanes having heteromorphic alkyl substituents with the distinct length k with the empirical formula , wherein at least two alkyl groups??of the distinct size ?each. ?is the number of alkyl radicals ?of the system??verifying the relation . The integer sequences of enantiomer pairs and achiral skeletons are given for substituted derivatives of monocyclic cycloalkane for n = 3, 4 and k = 3, 4, 5. The composite stereoisomerism of this particular compound is also highlighted.
