Db. Davies et al., H-1-NMR INVESTIGATION OF SELF-ASSOCIATION OF AROMATIC DRUG MOLECULES IN AQUEOUS-SOLUTION - STRUCTURAL AND THERMODYNAMICAL ANALYSIS, Journal of the Chemical Society. Faraday transactions, 92(3), 1996, pp. 383-390
Citations number
36
Categorie Soggetti
Chemistry Physical","Physics, Atomic, Molecular & Chemical
Self-association of aromatic drug molecules, proflavine (PF), Acridine
Orange (AO), ethidium bromide (EB) and actinomycin D (ActD), in aqueo
us 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 f
or a qualitative determination of their self-association, i.e. the mut
ual arrangement of the drug molecules in the complexes. Concentration
and temperature dependences of proton chemical shifts of the drugs hav
e been measured. Experimental results have been analysed using indefin
ite non-cooperative and cooperative models of molecular self-associati
on, enabling the determination of equilibrium reaction constants, para
meters 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 dime
r structures of PF, AO, EB and ActD have been constructed using calcul
ated 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.