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The Internal Relation between Quantum Chemical Descriptors and Empirical Constants of Polychlorinated Compounds.

ABSTRACT: Quantum chemical descriptors and empirical parameters are two different types of chemical parameters that play the fundamental roles in chemical reactivity and model development. However, previous studies have lacked detail regarding the relationship between quantum chemical descriptors and empirical constants. We selected polychlorinated biphenyls (PCBs) as an object to investigate the intrinsic correlation between 16 quantum chemical descriptors and Hammett constants. The results exhibited extremely high linearity for ? with Q_xx/yy/zz, ? and E_HOMO based on the meta-position grouping. Polychlorinated dibenzodioxins (PCDDs) and polychlorinated naphthalenes (PCNs) congeners, as two independent compounds, validated the reliability of the relationship. The meta-substituent grouping method between ? and ? was successfully used to predict the rate constant (k) for ^•OH oxidation of PCBs, as well as the octanol/water partition coefficient (logK_OW) and aqueous solubility (-logS_W) of PCDDs, and exhibited excellent agreement with experimental measurements. Revealing the intrinsic correlation underlying the empirical constant and quantum chemical descriptors can develop simpler and higher efficient model application in predicting the environmental behavior and chemical properties of compounds.

SUBMITTER: Fei J

PROVIDER: S-EPMC6278375 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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The Internal Relation between Quantum Chemical Descriptors and Empirical Constants of Polychlorinated Compounds.

Fei Jiangchi J Mao Qiming Q Peng Lu L Ye Tiantian T Yang Yuan Y Luo Shuang S

Molecules (Basel, Switzerland) 20181110 11

Quantum chemical descriptors and empirical parameters are two different types of chemical parameters that play the fundamental roles in chemical reactivity and model development. However, previous studies have lacked detail regarding the relationship between quantum chemical descriptors and empirical constants. We selected polychlorinated biphenyls (PCBs) as an object to investigate the intrinsic correlation between 16 quantum chemical descriptors and Hammett constants. The results exhibited ext ...[more]

PMID: 30423794

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Project description:According to the WHO, artemisinin-based combination therapies (ACTs) have been integral to the recent reduction in deaths due to Plasmodium falciparum malaria. ACT-resistant strains are an emerging problem and have evolved altered developmental stages, reducing exposure of the most susceptible stages to artemisinin drugs in popular ACTs. Lipophilicity, log K ow, is a guide in understanding and predicting pharmacokinetic properties such as terminal half-life which alters drug exposure. Consistent log K ow values are not necessarily available for artemisinin derivatives designed to extend terminal half-life, increase bioavailability, and reduce neurotoxicity. For other drugs used in ACTs, an assortment of experimental and computational log K ow values are available in the literature and in some cases, do not account for subtle but important differences between closely related structures such as between diastereomers. Quantum chemical methods such as density functional theory (DFT) used with an implicit solvent model allow for consistent comparison of physical properties including log K ow and distinguish between closely related structures. To this end, DFT, B3LYP/6-31G(d), with an implicit solvent model (SMD) was used to compute ΔG ow o and ΔG vow o for 1-octanol-water and olive oil-water partitions, respectively, for 21 antimalarial drugs: 12 artemisinin-based, 4 4-aminoquinolines and structurally similar pyronaridine, and 4 amino alcohols. The computed ΔG ow o was close to ΔG ow o calculated from experimental log K ow values from the literature where available, with a mean signed error of 2.3 kJ/mol and mean unsigned error of 3.7 kJ/mol. The results allow assignment of log K ow for α-and β-diastereomers of arteether, and prediction of log K ow for β-DHA and five experimental drugs. Linear least square analysis of log K ow and log K vow versus terminal elimination half-life showed strong linear relationships, once the data points for the 4-aminoquinoline drugs, mefloquine and pyronaridine were found to follow their own linear relationship, which is consistent with their different plasma protein binding. The linear relationship between the computed log K vow and terminal elimination half-life was particularly strong, R 2 = 0.99 and F = 467, and can be interpreted in terms of a simple pharmacokinetic model. Terminal elimination half-life for β-DHA and four experimental artemisinin drugs were estimated based on this linear relationship between log K vow and terminal t 1/2. The computed log K ow and log K vow values for epimers α- and β-DHA and α and β-arteether provide physical data that may be helpful in understanding their different pharmacokinetics and activity based on their different molecular geometries. Relative solubility of quinine and quinidine are found to be sensitive to thermal corrections to enthalpy and to vibrational entropy and do not follow the general trend of longer terminal t 1/2 with greater predicted log K ow. Geometric relaxation of α- and β-DHA in solvent and inclusion of thermal correction for enthalpy and entropy results in correct prediction that α-DHA is favored in aqueous environments compared to β-DHA. Predictions made regarding experimental drugs have implications regarding their potential use in response to artemisinin drug-resistant strains.

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The Internal Relation between Quantum Chemical Descriptors and Empirical Constants of Polychlorinated Compounds.

Publications

The Internal Relation between Quantum Chemical Descriptors and Empirical Constants of Polychlorinated Compounds.

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