Hetero-association Of Aromatic Molecules Research Articles

Physicochemical Mechanisms of Synergistic Biological Action of Combinations of Aromatic Heterocyclic Compounds

The mechanisms of synergistic biological effects observed in the simultaneous use of aromatic heterocyclic compounds in combination are reviewed, and the specific biological role of heteroassociation of aromatic molecules is discussed.

Relation between structure and enthalpy for stacking interactions of aromatic molecules

An approximately linear correlation has been found between the enthalpy of complexation and the area of overlap of the chromophores using published structural and thermodynamical data on the self- and hetero-association of aromatic molecules measured under similar solution conditions. This finding is consistent with the assumption that short-range van-der-Waals forces dominate over other contributions to the enthalpy of stacking of aromatic molecules. It provides a ‘model-independent’ approach for a priori estimation of the enthalpy of aromatic–aromatic stacking interactions from knowledge of the structural properties or vice versa.

Обобщенная статистико-термодинамическая модель гетероассоциации ароматических молекул в водном растворе для анализа данных ЯМР-спектроскопии

Обобщенная статистико-термодинамическая модель гетероассоциации ароматических молекул в водном растворе для анализа данных ЯМР-спектроскопии

1 H NMR investigation of the hetero-association of aromatic molecules in aqueous solution: factors involved in the stabilization of complexes of daunomycin and acridine drugs

1 H NMR investigation of the hetero-association of aromatic molecules in aqueous solution: factors involved in the stabilization of complexes of daunomycin and acridine drugs

1H NMR investigation of the hetero-association of aromatic molecules in aqueous solution: factors involved in the stabilization of complexes of daunomycin and acridine drugs

Hetero-association of the anthracycline drug, daunomycin (DAU), with typical mutagens, the acridine dyes proflavine (PF) and acridine orange (AO), has been studied by 500 MHz 1H NMR spectroscopy as a function of concentration and temperature in 0.1 mol dm−3 phosphate buffered aqueous solutions at pD = 7.1. The results have been analysed in terms of a statistical-thermodynamical model of hetero-association of aromatic molecules, described previously [Davies, D. B., Veselkov, D. A., and Veselkov, A. N., 1999, Molec. Phys., 97, 439], but generalized in this work, so that there is no limitation on the magnitudes of the self-association constants of the interacting molecules. Expressions suitable for the analysis of NMR parameters of both components in the mixed solution have been developed enabling both the structural and thermodynamic properties of hetero-association to be determined. The magnitude of the equilibrium constant for hetero-association of PF + DAU is found to be substantially higher than the self-association constants of these molecules, whereas that for hetero-association of AO + DAU is intermediate between the equilibrium constants of self-association of AO and DAU. Intermolecular cross-peaks observed in 2D-ROESY spectra of PF + DAU mixed solutions are consistent with formation of a hetero-association complex in which an intermolecular hydrogen bond can form between either of the 3,6-diamino groups of the PF chromophore and the 9-MeCO group of DAU, which is in contrast to AO + DAU hetero-association, where such hydrogen bonds are unable to form. Quantitative structural and thermodynamical analysis of PF + DAU complexation is consistent with an intermolecular hydrogen bond contributing to the stability of the hetero-complex in aqueous solution. The NMR results show that hydrophobic interactions play a substantial role in the stabilization of the AO-DAU complex, characterized by a relatively small entropy change on complexation, compared to the PF-DAU hetero-complex, which is mainly stabilized by hydrogen bond and dispersive van der Waals interactions.

Structure and thermodynamics of the hetero-association of aromatic molecules in aqueous solution determined by NMR spectroscopy

Structure and thermodynamics of the hetero-association of aromatic molecules in aqueous solution determined by NMR spectroscopy

Structure and thermodynamics of the hetero-association of aromatic molecules in aqueous solution determined by NMR spectroscopy

A statistical-thermodynamical model of hetero-association, in which molecules form indefinite aggregates for both self-association and hetero-association, has been developed in this work to analyse the NMR parameters of component molecules in mixed solutions. The NMR analysis has been used to investigate the hetero-association of the phenanthridinium drug molecules, ethidium bromide (EB) and propidium iodide (PI), and the method has been shown to be self-consistent by the same results being given for two independent sets of experiments having either PI or EB constant and the other varied. The magnitudes of the hetero-association parameters (equilibrium reaction constants and thermodynamic parameters, entropy and free energy) for the phenanthridinium drugs, PI and EB, are found to be intermediate between those observed for self-association of these molecules, whereas the enthalpy of hetero-association of EB + PI is similar to that for self-association of these molecules in solution. The most favourable structure of the PI + EB 1:1 hetero-association complex has been determined from the calculated values of the induced chemical shifts of the drug protons and it is found to be similar to that for PI determined in this work, and with EB determined previously. The results show that the size and charge of the side chains of EB [R = CH2CH3] and PI [R = (CH2)3N+(CH2CH3)2CH3] significantly influence the thermodynamics of molecular complexation but not the structures of the complexes, which are influenced more by the disposition of the phenyl group side chains.