Determination of Individual Proton Affinities of Ofloxacin from its UV−Vis Absorption, Fluorescence and Charge-Transfer Spectra: Effect of Inclusion in β-Cyclodextrin on the Proton Affinities

Abstract

Individual proton affinities of the four dissociable functional groups of (+/-)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid (commonly called "ofloxacin" and to be denoted henceforth as OflH), have been determined from the pH-dependent variation of the UV-vis absorption and fluorescence spectra of the compound itself and of its charge transfer complexes (CT) with p-bromanil and p-chloranil (in aqueous medium containing 0.1% ethanol, v/v). To utilize the CT spectra for determination of the proton affinity of the anilinic N, the CT absorption band of the ofloxacin-p-bromanil complex has been studied by changing the pH of the medium. Further, the effect of inclusion on the proton affinities of the four dissociable groups of OflH has been studied in presence of beta-cyclodextrin (beta-CD). Two pK(a) values corresponding to anilinic and tertiary N atoms change, whereas those corresponding to phenolic -OH and aromatic -COOH groups remain unchanged by the addition of beta-CD, a fact that indicates partial inclusion of the ofloxacin molecule in beta-CD. Formation constant and related thermodynamic parameters for the OflH(2)(+).beta-CD inclusion complex in aqueous solution have been determined from absorption intensities. A general relation between pK(a) values of guests having proton-releasing functional groups and formation constants of the inclusion complexes of the protonated and deprotonated forms with a host molecule has been utilized for determination of the formation constant of the OflH(3)(+2).beta-CD complex from the pK(a) values of OflH(3)(+2) in the presence and absence of beta-CD, along with the formation constant of the OflH(2)(+).beta-CD complex. Results of the present study reveal that the N-methylpiperazinyl moiety of ofloxacin is included in beta-CD, and the remaining part of the guest molecule remains outside. Also, in molecular interaction with quinone-type electron acceptors, charge transfer occurs from the aromatic part of the ofloxacin molecule, which is conjugated with the anilinic N atom of ofloxacin.

Study on the separation of ofloxacin enantiomers by hydroxyl-propyl-β-cyclodextrin as a chiral selector in capillary electrophoresis: a computational approach

“…Deep insertion of guest molecules inside the host results in strong van der Waals effects, a process characterized by negative enthalpy changes and negative entropy changes. Similar results were experimentally obtained for the inclusion complex formation of OFL with bCD [49]. It was reported that the complexation was associated with an enthalpy change, DH, of -30.5 kcal mol -1 and an entropy change, DS, of -87.2 J mol -1 K -1 .…”

Cyclodextrin Based Spectral Changes

“…Whereas the study of acid-base equilibrium of 4-nitrophenol show that 4-nitrophenolate (the negatively charged basic form) has more affinity than the acidic (neutral) form. It has been claimed that the driving force of more stable inclusion complex of 4-nitrophenolate with β-CyD is the hydrogen bonding [17,18].…”

Biobased System Composed of Electrospun sc-PLA/POSS/Cyclodextrin Fibers To Remove Water Pollutants

“…Indeed, this effect was already reported with other dyes systems, capable of interacting with CD molecules. In particular, it was demonstrated that, as the result of inclusion complex formation, the guest molecule is surrounded by the hydrophobic microenvironment of the CD cavity. − This environmental change causes some modification of the chemical and physical properties of the guest molecule, such as equilibria and kinetic parameters and absorption coefficient. As an example, it was found that upon binding of phenolphthalein to β-CD cavity in aqueous solution at pH 10.5, the red-colored dianion form is rapidly transformed into a colorless lactonoid form .…”