| This paper describes quantum chemical and quantitative structure-activity relationships (QSAR) studies on isothiazolone and indole derivatives by density functional theory (DFT) and multiple linear regression analysis (MLR) method. The isothiazolones included two classes: 29 2-substituted-3-isothiazolones and 27 2-(substituted-phenyl)-3-isothiazolones. 13 indole-3-carboxaldehydes and 6 gramines are the two series of indole derivatives studied in this paper. The equilibrium geometries, the frontier molecular orbital compositions and the distribution of mulliken charges of 75 compounds above mentioned have been investigated and analyzed. Then a series of QSAR models with good fitting and predictive quality were obtained. 8 new 2-substituted-3-isothiazolone molecules were designed and their predicted antibacterial activities were obtained based on the QSAR model. The main investigative results are as follows:First, 2-substituted-3-isothiazolones: S(1) and N(2) atoms are the active sites and 5-chloro derivatives are more active against E.coli than unsubstituted analogues. The net charges of substituent R1 (QR1), the nucleophilic frontier electron density of C(5) atom ( fC(5)N), the number of halogen on aromatic ring (nArX ), octanol-water partition coefficient ( LogP ) and the number of 6-membered rings ( nR 06) play the predominant role in antibacterial activity against E.coli. 6 in 8 new molecules designed show high antibacterial activity which calculate using the obtained QSAR model.Second, 2-(substituted-phenyl)-3-isothiazolones: Heterocyclic ring is the active position of this kind of compounds. LUMO orbital is important for the bioactivity of isothiazolones. The obtained QSAR model demonstrates that substituent R1, number of ethers on aromatic ring ( nArOR ), net charges of C(7) atom ( QC(7)) and dipole-dipole energy ( Ed ) are the principal facrors affecting the bioactivity of this set of compounds.Third, indole-3-carboxaldehydes: The right part of pyrrole ring, aldehyde group and C(7) atom are the active sites interaction with biological acceptor molecules. Bond length of N(1)-C(2) ( L1 ,2), bond order of C(3)-C(10) ( BO3 ,10) and the electrophilic frontier electron density of N(1) atom ( fN(1)E) are found to be the prominent ones affecting the antifouling activity of indole-3-carboxaldehydes. Moreover, antifouling activity is proportional to indicator parameter I 2 and octanol-water partition coefficient ( LogP ).Fourth, gramines: Correlation analysis suggests that antifouling activity is related closely to the energy of the highest occupied molecular orbital (εH). Octanol-water partition coefficient ( LogP ) favors the activity and increasing moderately the lipophilicity of gramines enhances the antifouling activity. |
