Phenylalanine and tyrosine methyl ester intramolecular interactions and conformational analysis by 1 H NMR and infrared spectroscopies and theoretical calculations Rodrigo A. Cormanich a , Lucas C. Ducati b , Cláudio F. Tormena a , Roberto Rittner a,⇑ a Chemistry Institute, University of Campinas, P.O. Box 6154, 13083-970 Campinas, Brazil b Chemistry Institute, University of São Paulo, P.O. Box 26077, 05508-900 São Paulo, Brazil highlights  Phenylalanine and tyrosine were investigated by theoretical and experimental methods.  The lowest energy conformers are not stabilized by hydrogen bonding.  Steric and hyperconjugative effects were analyzed for all conformers.  Several theoretical methods were used to explain the conformational preferences. graphical abstract article info Article history: Received 25 September 2013 Received in revised form 29 November 2013 Accepted 21 December 2013 Available online 3 January 2014 Keywords: Conformational analysis Amino acid methyl ester derivatives 1 H NMR spectroscopy Infrared spectroscopy Intramolecular hydrogen bonding Stereoelectronic effects abstract Amino acid conformational analysis in solution are scarce, since these compounds present a bipolar zwit- terionic structure ( + H 3 NACHRACOO  ) in these media. Also, intramolecular hydrogen bonds have been classified as the sole interactions governing amino acid conformational behavior in the literature. In the present work we propose phenylalanine and tyrosine methyl ester conformational studies in different solvents by 1 H NMR and infrared spectroscopies and theoretical calculations. Both experimental and the- oretical results are in agreement and suggest that the conformational behavior of the phenylalanine and tyrosine methyl esters are similar and are dictated by the interplay between steric and hyperconjugative interactions. Ó 2014 Elsevier B.V. All rights reserved. Introduction The understanding of amino acids conformational behavior in solution is essential for a deep recognition of the complex pro- tein geometries to which such compounds give rise [1–4]. How- ever, intramolecular hydrogen bonds (IHB) have been commonly considered the sole interaction governing amino acid conforma- tional isomerism since the very beginning of amino acid conforma- tional studies in the literatures [5–18]. Recently, it was found that the balance between steric and hyperconjugative effects and not IHBs are actually the main forces dictating the conformational behavior of a considerable range of amino acids and amino acid esters [19–23]. Moreover, few to none conformational studies of amino acids in solution can be found in the literature, particularly using NMR 1386-1425/$ - see front matter Ó 2014 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.saa.2013.12.088 ⇑ Corresponding author. Tel./fax: +55 19 3521 3150; fax: +55 19 3521 3023. E-mail address: rittner@iqm.unicamp.br (R. Rittner). Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 123 (2014) 482–489 Contents lists available at ScienceDirect Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy journal homepage: www.elsevier.com/locate/saa