DOI: 10.1002/cphc.200800383 IR Low-Temperature Matrix and ab Initio Study on b-Alanine Conformers Jan Cz. Dobrowolski,* [a, c] Michał H. Jamróz, [c] Robert Kołos, [d] Joanna E. Rode, [c] and Joanna Sadlej* [a, b] 1. Introduction The natural occurence of b-amino acids is much lower than that of a-amino acids. In b-amino acids, the NH 2 group is locat- ed at the second, b-carbon atom and the COOH group remains attached to the a-position. Some b-amino acids, such as b-ala- nine and b-aminoisobutyric acid, occur naturally and have been found in their free forms as metabolites in mammals as uracil and thymine are catabolized to b-alanine and b-aminoi- sobutyric acid. [1,2] A few b-amino acids have been isolated from plants, bacteria, and invertebrates. [1,3] b-Amino acids are moiet- ies of several pharmacologically active compounds such as an- tibiotics, [4] antitumor agents, [5–10] or antifungal agents. [11] The presence of the additional carbon atom in the backbone of a b-amino acid results in different properties of b-peptides, such that they exhibit higher stability against peptidases. [12,13] Investigations of b-peptides showed that they have an enor- mous potential for secondary structure formation, as docu- mented in numerous comprehensive reviews. [14–17] The interest in this group of compounds stems from their antimicrobial ap- plications; b-peptides containing b-amino acids occur very rarely in nature and they contain exclusively b-alanine deriva- tives. [1] Moreover, they form a more stable helix than a-pep- tides. For these reasons, b-peptide-based antibiotics are being explored for evading antibiotic resistance. Such an example is magainin—a powerful peptide-based antibiotic. [18–21] b-Alanine (3-aminopropionic acid, Scheme 1), together with b-aminoisobutyric acid, are the main naturally occurring b- amino acids. [1] b-Alanine is formed by the degradation of dihy- drouracil and caronosine (dipeptide). In vivo, the pyrimidine degradation pathway is the main route for the synthesis of b- alanine in human beings. [22] b-Alanine is a structural analogue of GABA (g-aminobutyric acid) and glycine, which are the major inhibitory neurotransmitters in the central nervous system. It has been suggested that b-alanine itself might func- tion as a neurotransmitter since it is an agonist of both the gly- cine and GABA A receptors. [23,24] Also, it is a component of pan- tothenic acid (vitamin B5), coenzyme A, and the naturally oc- curring peptides caronosine and anserine. [25,26] Under normal conditions it is metabolized into acetic acid. b-Alanine (Scheme 1) has no chiral center and is conforma- tionally labile due to the possibility of free rotation about the single bonds between the non-hydrogen atoms. Its high tor- sional flexibility results in a number of conformers of its neutral form in the gas phase. Two conformers of this molecule have previously been found by McGlone and Godfrey, [27] while four conformers have recently been observed by Fourier transform microwave spectroscopy with pulsed supersonic jet with laser For the first time the argon-matrix low-temperature FTIR spectra of b-alanine are recorded. They reveal a quite complicated spec- tral pattern which suggests the presence of several b-alanine conformers in the matrix. To interpret the spectra, the eighteen b-alanine conformers, stable in the gas phase, are estimated at the B3LYP and MP2 levels combined with the aug-cc-pVDZ. Ten low-energy structures are reoptimized at the QCISD/aug-cc-pVDZ and B3LYP and MP2 levels by using the aug-cc-pVTZ basis sets. Assignment of the experimental spectra is undertaken on the basis of the calculated B3LYP/aug-cc-pVDZ anharmonic IR fre- quencies as well as careful estimation of the conformer popula- tion. The presence of at least three b-alanine conformers is dem- onstrated. The detailed analysis of IR spectra points to the possi- ble presence of five additional b-alanine conformers. Scheme 1. Structure of b-alanine. [a] Prof. J. Cz. Dobrowolski, Prof. J. Sadlej National Medicines Institute 30/34 Chełmska Street, 00-725 Warsaw (Poland) Fax: (+ 48)22-841-0652 E-mail: janek@il.waw.pl [b] Prof. J. Sadlej Faculty of Chemistry, Warsaw University 1 Pasteura Street, 02-093 Warsaw (Poland) Fax: (+ 48)22-822-5996 E-mail: sadlej@chem.uw.edu.pl [c] Prof. J. Cz. Dobrowolski, Dr. M. H. Jamróz, Dr. J. E. Rode Industrial Chemistry Research Institute 8 Rydygiera Street, 01-793 Warsaw (Poland) [d] Prof. R. Kołos Institute of Physical Chemistry, PAN 44 Kasprzaka Street, 01-224 Warsaw (Poland) Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cphc.200800383. 2042 # 2008 Wiley-VCH Verlag GmbH&Co. KGaA, Weinheim ChemPhysChem 2008, 9, 2042 – 2051