Aggregation of 1,3,7-trimethylxanthine with methylene blue in aqueous solution

Abstract

We have studied self-association of aromatic molecules of the thiazine dye methylene blue in aqueous solution, using a dimer model. We have determined the dimerization equilibrium constant for the dye molecules K D = 3900 ± 800 M -1 at T = 293 K. We have decomposed the experimental spectrum into dimer and monomer components. Using the ratio of the molar absorption coefficients for two absorption bands of the dimer spectrum, we obtained the "average" value of the angle between the electronic transition moments of the molecules in the dimers, α = 48 o .We have studied heteroassociation of methylene blue (MB) and 1,3,7-trimethylxanthine (caffeine) molecules in aqueous solution. We have calculated the heteroassociation constant as 200 ± 34 M -1 . We conclude that heteroassociation of methylene blue and caffeine molecules leads to a lower effective dye concentration in solution, which hypothetically may affect its biological activity.We have determined the values of the Gibbs free energy, the enthalpy, and the entropy for dimerization of methylene blue molecules: ∆G 293 = -(20 ± 3) kJ/mol, ∆H = -(25 ± 9) kJ/mol, ∆S 293 = -(17 ± 6) J/mol⋅K; and for methylene blue-caffeine heteroassociation: ∆G 293 = -(13 ± 3) kJ/mol, ∆H = -(14 ± 10) kJ/mol, ∆S 293 = -(2.4 ± 0.2) J/mol⋅K, respectively. We have shown that the methylene blue aggregates and the heteroassociates with caffeine are predominantly stabilized by dispersion interactions between the chromophore molecules in the associates.

Complexation of heterocyclic ligands with DNA in aqueous solution

“…According to the model, the total molar absorption coefficient ε can be represented as [27,28]: Table 1, and agree well with the self-association constants obtained for the indicated dyes by spectrophotometry [26] and NMR spectroscopy [30]. Analysis of the self-association parameters obtained suggest that aggregation of phenothiazine dyes is more favorable than aggregation of the acridine dye PF.…”

“…For the selected dye concentrations, molecular aggregation effects should appear [26], and accordingly as the preliminary step in analysis of the ligand-DNA interaction we studied self-association of PF and Th. Self-association of methylene blue was studied previously in [27].…”

“…For PF, an increase in concentration leads to a decrease in the intensity of the absorption bands and a small shift of the spectra toward shorter wavelengths. The spectral features described are an indicator of stacked aggregation of the molecules by means of vertical stacking of the aromatic chromophores [26][27][28][29]. The presence of isosbestic points in the spectra of PF and Th (λ ≈ 475 nm and 568 nm) suggests the absence of associates of higher order than dimers in the selected range of dye concentrations (2.5⋅10 Self-association of the dyes in an aqueous solution was analyzed, as earlier in [27,28], based on experimental concentration dependences of the molar absorption coefficient of the molecules at wavelengths corresponding to the absorption maxima of the ligands in monomer form (Fig.…”

Hetero-association of aromatic molecules in aqueous solution

“…Hetero-association in Drug-xanthine systems has been extensively studied by NMR, UV-vis, Fluorescence spectroscopies, titration microcalorimetry, partitioning in waterorganic mixture, molecular modelling and other techniques for the following aromatic drugs: daunomycin (DAU) [127,[133][134][135][136], doxorubicin (DOX) [33,42,127,[137][138][139], actinomycin D (AMD) and its derivatives [133,[140][141][142][143], benzene and its derivatives [122,144], novantrone/mitoxantrone (NOV) [42, 127, 135-137, 145, 146], nogalamycin (NOG) [138], norfloxacin (NOR) [135,136,147], camptothecins [139,148,149], quinoxaline [84], chloroquine [84], DAPI [150], phenothiazines [121,151,152], riboflavin [135,[153][154][155], porphyrins [156,157], acridine mutagens [53,54,124,125,[133][134]…”

Complexation of aromatic drugs with single-walled carbon nanotubes

“…(2), (6) can be further extended by means of introduction of other processes such as CNT aggregation, competitive binding of different types of ligands, etc. [ (Baranovskii et al 2006) have made an example of such analysis with respect to UV/Vis data for self-and hetero-association of aromatic molecules, resulting in equations which can be reduced to Eqs. (2), (6); (Evstigneev et al 2013) have provided an example of analysis with respect to ligand binding with strongly aggregating C 60 fullerene].…”