H-1 NMR investigation of self-association of aromatic drug molecules in aqueous solution - Structural and thermodynamical analysis

被引:103
作者
Davies, DB [1 ]
Djimant, LN [1 ]
Veselkov, AN [1 ]
机构
[1] SEVASTOPOL STATE TECH UNIV, DEPT PHYS, SEVASTOPOL 335053, UKRAINE
来源
JOURNAL OF THE CHEMICAL SOCIETY-FARADAY TRANSACTIONS | 1996年 / 92卷 / 03期
关键词
D O I
10.1039/ft9969200383
中图分类号
O64 [物理化学(理论化学)、化学物理学];
学科分类号
070304 ; 081704 ;
摘要
Self-association of aromatic drug molecules, proflavine (PF), Acridine Orange (AO), ethidium bromide (EB) and actinomycin D (ActD), in aqueous salt solution has been studied by one- and two-dimensional 500 MHz H-1 NMR spectroscopy. 2D-COSY and 2D-NOESY measurements were used for complete assignment of proton signals of EB and ActD in solution and for a qualitative determination of their self-association, i.e. the mutual arrangement of the drug molecules in the complexes. Concentration and temperature dependences of proton chemical shifts of the drugs have been measured. Experimental results have been analysed using indefinite non-cooperative and cooperative models of molecular self-association, enabling the determination of equilibrium reaction constants, parameters of cooperativity, the thermodynamical parameters (enthalpy and entropy) of the self-association reactions and the limiting values of drug proton chemical shifts in the complexes. The most favourable dimer structures of PF, AO, EB and ActD have been constructed using calculated values of induced chemical shifts of drug protons in conjunction with intermolecular NOEs. The results show that the drug chromophores have an antiparallel orientation in all the dimers studied.
引用
收藏
页码:383 / 390
页数:8
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