Methylparaben Isolated in Solid Argon: Structural Characterization and UV-Induced Conversion into Methylparaben Radical and Isomeric Ketenes Nihal Kus ̧ , †,‡ Sevgi H. Bayarı, § and Rui Fausto* ,† † Department of Chemistry, University of Coimbra, P-3004-535 Coimbra, Portugal ‡ Department of Physics, Anadolu University, 26470 Eskis ̧ ehir, Turkey § Department of Physics, Hacettepe University, 06800 Ankara, Turkey * S Supporting Information ABSTRACT: Methylparaben (methyl p-hydroxybenzoic acid; MP) is a widely used antimicrobial preservative, being the most frequently used antimicrobial preservative in cosmetics. The generalized use of MP has become controversial, with several recent reports of dangerous side effects. For example, the presence of MP in human breast tumors and its harmful effects on human skin exposed to the sunlight have been demonstrated. In spite of the important practical relevance of the compound and of the controversy about its practical use, its structural and photochemical characterization had not been undertaken hitherto. To fill this gap, in the present study, MP was isolated in solid argon (T = 15 K) and structurally characterized by a combined infrared spectroscopy/quantum chemistry approach. The potential energy surface (PES) of the molecule was investigated in detail, revealing the existence of two almost isoenergetic (ΔE 0 = 0.37 kJ mol -1 ) s-cis carboxylic ester low-energy conformers, with an estimated population ratio in the gas phase at room temperature (∼298 K) of ca. 0.83. The calculations also predicted the existence of two high-energy (ΔE 0 = ∼50 kJ mol -1 ) s-trans carboxylic ester conformers of MP. Upon isolation of the compound in an argon matrix, only the lowest energy conformer was found to survive, due to occurrence of extensive conformational cooling during matrix deposition. The infrared spectrum of this conformer was obtained and interpreted. In addition, the chemical processes resulting from in situ irradiation of the matrix-isolated MP with a broadband UV source (λ > 234 nm) were investigated, revealing extensive conversion of MP into highly reactive methylparaben radical and isomeric ketenes. These observations support the recent concerns regarding uses of MP, in particular when the compound has to be exposed to UV light. 1. INTRODUCTION Methylparaben (methyl p-hydroxybenzoate; MP) is a widely used antimicrobial preservative in cosmetics, food products, and pharmaceutical formulations. 1-3 It has been considered to meet most of the criteria of an ideal preservative: broad spectrum of antimicrobial activity, safe to use (i.e., relatively non-irritating, non-sensitizing, and of low toxicity), stable over a wide pH range, colorless, odorless (slight burnt flavor), non-volatile, sufficiently soluble in water to produce the effective concentration in aqueous phase, and cheap. 1,4-7 Methyl paraben consumption by humans (in food, cosmetics, and personal care products) is estimated to be larger than 50 mg/ day. 1 Though MP has been considered to have low acute and long- term toxicity, to have no carcinogenic and mutagenic activities, 1,8-10 and to be readily and completely absorbed through the skin and from the gastrointestinal tract, 1 several studies have reported that small amounts of the compound remain unhydrolyzed in the epidermis and body tissues. 11-13 For example, the presence of MP in human breast tumors has been recently reported, 14,15 and its harmful effects on human skin exposed to the sun’s UV light have been demonstra- ted. 16-18 Such observations questioned the generalized use of MP. In spite of the practical relevance of the compound, its structural and photochemical characterization had not been undertaken hitherto. In fact, most of the studies on MP have been centered on development of different approaches for its quantitative determination (using chromatographic or spectro- metric techniques) 19-28 or evaluation of its biological effects. 1,29-31 Since MP also has adequate properties to act as a nonlinear optical material (the simultaneous presence in the Received: August 21, 2013 Revised: October 1, 2013 Published: October 1, 2013 Article pubs.acs.org/JPCB © 2013 American Chemical Society 13543 dx.doi.org/10.1021/jp408366x | J. Phys. Chem. B 2013, 117, 13543-13555