Physical Chemistry Communications, Volume 3 Issue 2, October 2016 www.bacpl.org/j/pcc
Mechanism of Oxidation of Theophylline by Silver (III) Periodate Complex in Aqueous Alkaline Medium Arunkumar T. Buddanavar and Sharanappa T. Nandibewoor* P. G. Department of studies in Chemistry, Karnatak University, Dharwad – 580 003, India Email address: stnandibewoor@yahoo.com Tel: +918362215286; Fax: +918362747884 Abstract The kinetics of oxidation of theophylline (TP) by diperiodatoargentate (III) (DPA) in aqueous alkaline medium at a constant ionic strength of 0.31 mol dm−3 was studied spectrophotometrically. The reaction between TP and DPA in alkaline medium exhibits 1:2 stoichiometry. The reaction is of the first order with respect to [DPA] and has a zero order in [TP] and unit order in [alkali]. The main oxidation product was identified as 3‐methyl‐2,6‐dioxo‐2,3dihydro‐6H‐purine‐1(7H)‐carbaldehyde by spot test, FT‐IR and LC‐MS spectral studies. A probable mechanism was proposed; the activation parameters were computed and discussed. Keywords Oxidation, Diperiodatoargentate, Theophylline and Spectroscopy
Introduction Theophylline, also known as 1,3‐dimethylxanthine, (TP) is a methylxanthine drug used in therapy for respiratory diseases such as chronic obstructive pulmonary disease (COPD), asthma and infant apnea. It blocks the action of adenosine, an inhibitor neurotransmitter that induces sleep, contracts the smooth muscles and relaxes the cardiac muscle, strengthens right heart function and diaphragm movement. It is one of the most commonly used bronchodilators and respiratory stimulants for the treatment of asthma and lung diseases of adults [1, 2]. It has been shown that theophylline may reverse the clinical observations of steroid insensitivity in patients with COPD and asthmatics that are active smokers via a distinctly separate mechanism. Like other methylated xanthine derivatives, TP is both a competitive nonselective phosphodiesterase inhibitor [1] and nonselective adenosine receptor antagonist [2]. The presence and accumulation of theophylline in aquatic environments, at low concentrations, may pose threats to the ecosystem and human health. The silver (III) periodate complex (DPA) is a powerful oxidizing agent in an alkaline medium with a reduction potential [3] of 1.74 V. It is widely used as a volumetric reagent for the determination of various organic and inorganic species [4, 5]. To study the kinetics of oxidation of various organic substrates, DPA was used as an oxidizing agent [6‐8]. They generally found that order with respect to both the oxidant and substrate was unity and [OHˉ] was found to enhance the rate of reaction. It was also observed that they did not arrive the possible active species of DPA in alkali and therefore, they proposed mechanisms by generalizing the DPA as [Ag(HL)L](X+1) −. However, Kumar et al. [9‐11] made an effort to give evidence for the reactive form of DPA at an alkaline pH. In the present investigation, different observations were observed and we have obtained evidence for the reactive species for DPA in an alkaline medium. A literature survey reveals that there are no reports on the mechanism of oxidation of theophylline by DPA in an alkaline medium. In view of the pharmaceutical importance of TP and in order to understand the active species of the oxidant and to identify a suitable mechanism, the title reaction was investigated. Such studies are of much significance in understanding the mechanistic profile of theophylline in redox reactions and provide an insight into the interaction of metal ions with the substrate and its mode of action in biological systems. Hence, the present investigation is aimed at checking the reactivity of TP towards DPA and to arrive at the plausible mechanism. An understanding of the mechanism allows the chemistry to be interpreted, understood and predicted.
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