Equilibrium constants for association of caffeine and theophylline with aromatic salts in aqueous solutions studied by ¹H NMR chemical shift measurements

Abstract

The interaction of caffeine and theophylline with sodium benzoate and sodium salicylate has been studied in deuterium oxide at 35°C by measnring the aromatic salt-induced changes in the chemical shifts of the N-methyl protons. Taking into account the self-association of the N-methylxanthines, on the basis of a 1 : 1 complexation model the association constants for caffein-odium benzoate, theophylline-sodium benzoate, deine-sodium salicylate and theophylline-sodium salicylate were-found to be 2.1 0.1, 1.5 f 0.2, 7.8* 0.2 and 5.0 =t 0.2 1 mol-l, respectively.

Complexation of Biologically Active Aromatic Compounds with DNA in the Presence of Theophylline

“…It is found in Table 1 that the magnitudes of the equilibrium constants of THP-ligand hetero-association are in general similar to those for the hetero-association of CAF with the same ligands, although being somewhat higher (except for the NOV-THP system). In previous work [19,20], it was shown that the absence of the 7-methyl group in the structure of THP molecules should lead to more compact stacking of the aromatic chromophores than in CAF. In the case of the sandwich-type hetero-association discussed in this work, compact stacking will always result in effective dispersive interactions of aromatic chromophore currents and, as a consequence, may lead to the increase in the hetero-association constant of THP compared to CAF with the same aromatic drugs.…”

“…However, caffeine is not the only methylxanthine compound present in significant amounts in human blood plasma on consumption of caffeinated food. There are also relatively large amounts of caffeine derivatives such as paraxanthine, theophylline and theobromine [1], which, in principle, can act as effective interceptors of aromatic BACs, though there is little known about the hetero-association of these compounds with BACs and their influence on drug-DNA binding except a few reports of the complexation of theophylline with the dye Acridine Orange [14], and some nucleotide derivatives [18][19][20][21]. Theophylline (THP, Fig.…”

Hetero-association of aromatic molecules in aqueous solution

“…Studies on hetero-association involving pyrazole analogues of nucleic acids [70], 2-ring quinoxaline [84], chloroquine [84] and indole [32] derivatives, some aromatic aminoacids [32], and 1-ring sodium benzoate and salicylate [104] reported magnitudes of binding constants similar to or within the same region of discrepancy as for the corresponding purines or pyrimidines.…”

Solvation and Ion‐Pairing Effects of Choline Acetate Electrolyte in Protic and Aprotic Solvents Studied by NMR Titrations

“…NMR titration experiments offer the possibility to characterize the thermodynamics of association between the ions as well as the ions and the solvent molecules in electrolyte solutions. [68][69][70][71] 1 H chemical shift perturbations (CSPs) are shown in Figure 2 In DMSO-d 6 the strongest non-linear CSP is observed for the À OH group of choline, with a maximum deviation of about 0.7 ppm downfield (Figure 2 3), the rest are linear fits.…”