The effects of conformation and zwitterionic tautomerism on the structural and vibrational spectral data of anserine K. Balci a, *, Y. Akkaya a , S. Akyuz b , W.B. Collier c , M.C. Stricker d , D.D. Stover c , G. Ritzhaupt c , A. Koch e , E. Kleinpeter e a Istanbul University, Faculty of Science, Department of Physics, Vezneciler, 34134, Istanbul, Turkey b Istanbul Kultur University, Department of Physics, Atakoy Yerleskesi, 34156, Bakirkoy, Istanbul, Turkey c Oral Roberts University, Department of Chemistry and Biology, Tulsa, OK 74171, USA d Kao Specialties Americas, LLC, 243 Woodbine St., High Point, NC 27260, USA e Potsdam University, Department of Chemistry, Karl-Liebknecht-Str. 24-25, D-14476 Potsdam (Golm), Germany A R T I C L E I N F O Article history: Received 16 March 2016 Received in revised form 19 July 2016 Accepted 9 August 2016 Available online 12 August 2016 Keywords: Anserine Matrix IR spectrum Tautomerism SQM-FF Dual scale factors A B S T R A C T In this study, the stable conformers of neutral anserine were searched by molecular dynamics simulations and energy minimization calculations using the MM2 force field. Thermochemical calculations at B3LYP/6-31G(d) level of theory followed these preliminary calculations. The results confirmed that neutral anserine has quite a flexible structure and many stable gauche and trans conformers at room temperature. Nevertheless, two are considerably more favourable in energy than the others and expected to dominate the gas-phase and matrix IR spectra of the molecule. The corresponding structural and vibrational spectral data for these two conformers of neutral anserine, whose relative stabilities were also examined by high-accuracy energy calculations carried out using G3MP2B3 method, and for the most stable conformer of anserine in zwitterion form were calculated at B3LYP/6-311++G(d,p) level of theory. The calculated harmonic force constants were refined using the Scaled Quantum Mechanical Force Field (SQM-FF) method and then used to produce the refined wavenumbers, potential energy distributions (PEDs) and IR and Raman intensities. These refined data together with the scaled harmonic wavenumbers obtained using another method, Dual Scale factors (DS), enabled us to correctly analyse the observed IR and Raman spectra of anserine and revealed the effects of conformation and zwitterionic tautomerism on its structural and vibrational spectral data. ã 2016 Elsevier B.V. All rights reserved. 1. Introduction Anserine (L-histidine-b-alanyl-3-methyl) and its parent mole- cule carnosine (L-histidine-b-alanyl) are two histidine derivatives, both of which are found in skeletal muscles, the heart and the central nervous system at very high concentrations [1–3]. These molecules are known to play physiological roles in the muscle and brain and have potential for therapeutic applications for individu- als with Wilson’s disease, and against the pathogenesis of Parkinson’s disease and related disorders [4]. A remarkable number of published papers on the structural and vibrational spectral data of histidine dipeptides are present in the literature. While these studies are mostly on L-histidine [5–7], carnosine and its various metal complexes [8–15], only few of them have specifically focused on anserine which is a methyl substituted derivative of carnosine. To our best knowledge, the paper by Thomas et al. [16], on the interpretation of surface enhanced Raman spectrum (SERS) of anserine in silver colloid is the first published study on the structural and vibrational spectral properties of the molecule. This was followed by our previous study [17], where an interpretation of the dispersive Micro Raman, FT-Raman and FT-IR spectra of solid anserine and its aqueous solutions was given. In solid/liquid phase or in solvents with a low pH value (between 5 and 9) amino acids prefer to be in “zwitterion” form. This is also true for histidine dipeptide and its two derivatives carnosine and anserine [5,8,11,17]. Normally, this forces the use of gas-phase or matrix-isolation IR spectroscopic techniques in spectroscopic investigations on the neutral forms of these molecules. However the high sublimation temperatures and extremely low vapor pressures of these molecules leave matrix- isolation IR spectroscopy as practically the only viable option for * Corresponding author. E-mail addresses: kbalci@istanbul.edu.tr, kbalci@lycos.com (K. Balci). http://dx.doi.org/10.1016/j.vibspec.2016.08.003 0924-2031/ã 2016 Elsevier B.V. All rights reserved. Vibrational Spectroscopy 86 (2016) 277–289 Contents lists available at ScienceDirect Vibrational Spectroscopy journa l homepage: www.e lsevier.com/locate/vibspec