30 March 2001 Chemical Physics Letters 337 22001) 143±150 www.elsevier.nl/locate/cplett Non-ionic and zwitterionic forms of neutral arginine ± an ab initio study Piotr Skurski a,b, Maciej Gutowski b,c, Robyn Barrios a, Jack Simons a,* a Henry Eyring Center for Theoretical Chemistry, Department of Chemistry, University of Utah, Salt Lake City, UT 84112, USA b Department of Chemistry, University of Gdansk, ul. Sobieskiego 18, 80-952 Gdansk, Poland c Environmental Molecular Sciences Laboratory, Paci®c Northwest National Laboratory Richland, WA99352, USA Received 14 November 2000; in ®nal form 23 January 2001 Abstract Six low-energy structures of arginine were studied at the zero-point corrected CCSD/6-31++G2d,p)+52sp)//MP2/ 6-31++G2d,p)+52sp) level. Two new non-ionic structures were identi®ed, one of which is 1.75 kcal/mol lower than any previously reported structure. Two new zwitterion conformers are lower in energy than any previously reported zwitterion. The lowest non-ionic structure is lower in energy than the lowest zwitterion by 2.8 kcal/mol at our highest level of theory, and for no basis or theory level is a zwitterion structure suggested to be the global minimum. Finally, we also examined, at Koopmans' theorem level, the electron binding energies of the six structures. Ó 2001 Elsevier Science B.V. All rights reserved. 1. Introduction gas phase [3] but these ®ndings were inconclusive [4]. Other recent eorts concentrated on hydrated It is well known that, in aqueous solutions at [5,6], protonated [3,7,8], and alkali cationized [7±9] pH 7, aminoacids exist primarily in their zwit- aminoacids. terionic forms with the carboxyl group deproto- We have recently suggested stabilizing the nated and one of the nitrogen atoms protonated. zwitterion form of an aminoacid in the gas phase In contrast, the zwitterionic forms are usually with an excess electron [10] and it was via this higher in energy in the gas phase than the corre- route that we began our exploration of various sponding non-zwitterion H2N±CHR±COOH tau- arginine isomer energetics. Our reasoning is that tomers. Moreover, for some aminoacids 2e.g., the zwitterion form of an aminoacid would possess glycine), the zwitterionic structure does not even a larger dipole moment than the non-zwitterion correspond to a local minimum on the gas-phase form. It is well established that a molecule with a potential energy surface [1,2]. There have been dipole moment larger than ca. 2.5 D binds an ex- attempts to identify a zwitterionic tautomer of a cess electron [11] with an electron binding energy neutral aminoacid which is globally stable in the roughly correlated with the magnitude of the di- pole moment [12]. Therefore, we anticipated the instability of the zwitterion relative to the non- * Corresponding author. Fax: +1-801-581-8433. zwitterion structure might be reversed by the E-mail address: [email protected] 2J. Simons). excess electron binding energy. It is our plan to 0009-2614/01/$ - see front matter Ó 2001 Elsevier Science B.V. All rights reserved. PII: S 0 0 0 9 - 2 6 1 4 2 0 1 ) 0 0 166-X 144 P. Skurski et al. / Chemical Physics Letters 337 62001) 143±150 report on our arginine anion ®ndings in a future thermodynamically unstable form may have a publication. However, because there is strong suciently long lifetime to be observed experi- current interest in arginine itself, we decided to put mentally. Moreover, the sources of arginine used forth our ®ndings on the neutral species at this in the Williams and Saykally experiments are dif- time. ferent. One employes solution electro spray at 37± In a recent study, we demonstrated that the 149°C; the other employes a heated pulsed beam instability of the zwitterion structure of glycine is source of pure arginine at 170°C. signi®cantly reduced by the attachment of an ex- The geometrical shapes of the protonated, so- cess electron as a result of which a local minimum diated, and cesiated arginine were probed in the develops on the anionic potential energy surface gas phase by using the ion mobility based ion [10]. However, its energy is still higher than that of chromatography method [7,9]. Unfortunately, the the anion based on the non-zwitterion isomer of qualitative structure of the protonated arginine glycine. This outcome may be related to the fact could not be unambiguously determined from that the proton anity of glycine of 211.9 kcal/mol these experiments. It has been suggested that the is the smallest among all 20 common naturally alkali cationized arginine forms a salt bridge occurring amino acids [7]. The largest proton af- structure, related to the zwitterion form of this ®nity of 251.2 kcal/mol is displayed by arginine [7], aminoacid. Results from the collisionally activated which possesses an extremely basic guanidine dissociation experiments of Williams et al. [13] and group. Therefore, we selected arginine for our the kinetic experiments of Cerda and Wesdemiotis study on stabilization through electron binding [14] indicated, however, that the structure of gas- which leads to the results presented here. phase arginine±alkali metal cation complexes de- The question of which tautomeric form of pends on the size of the alkali metal cation. For neutral arginine is dominant in the gas phase has Li and Na, the non-zwitterion arginine solvates recently been addressed in experimental studies the metal ion. For the larger metal ions, a salt [3,4,7,9,13,14]. Williams and co-workers [3] con- bridge is formed in which the arginine exists as a cluded, on the basis of black body infrared radi- zwitterion. ative dissociation plus Fourier transform-mass Maksic and Kovacevic 2MK), inspired by the spectrometry measurements, that protonated di- variety of intriguing experimental ®ndings, per- mers of arginine are bound in a salt-bridge. formed an extensive computational investigation Moreover, the results of their extensive computa- in order to ®nd the global minimum for neutral tional study at the BLYP/6-31GÃ and MP2/6-31GÃ arginine [15]. They concluded from their thorough levels suggested that a zwitterion form of arginine MP2 and B3LYP calculations using several basis is the global minimum on the potential energy sets, that the most stable structure is a non-ionic. surface, lower by 1 kcal/mol than the lowest non- These authors admitted, however, that the energy ionic tautomer. Saykally and co-workers [4], dierence between the lowest non-ionic and a pair however, did not con®rm the dominance of the of low lying zwitterion structures is relatively small zwitterion of arginine in their infrared cavity 2within 1±3 kcal/mol depending on the theoretical ringdown laser absorption spectroscopy experi- model applied) [15]. ments. The observed band at ca. 1700 cmÀ1, which As detailed above, our long-term goal is to de- is associated with the carbonyl stretch mode of a termine whether an excess electron can stabilize a carboxylic acid, implied the presence of a non- zwitterion structure of arginine. This goal requires ionic structure in their gas-phase sample. The ab- extensive knowledge about the potential energy sence of bands in the 1500±1660 cmÀ1 region, surface for the neutral species, and in this contri- which are associated with the carboxylate stretch bution we characterize what we have found to be modes, suggested a small or vanishing population the most promising neutral non-ionic and zwit- of the zwitterion. It was pointed out, however, that terionic structures. In addition to the structures there may be a signi®cant barrier that separates the characterized so far [3,15], we identi®ed two non- neutral and zwitterion forms of arginine and the zwitterion and two zwitterion structures that are P. Skurski et al. / Chemical Physics Letters 337 62001) 143±150 145 promising candidates. Their relative energies have In terms of atomic orbitals, we primarily used been determined at the MP2, B3LYP, and CCSD 6-31++G2d,p) [21,22] basis sets to describe the levels and their dipole moments have been calcu- neutral molecule. We supplemented this basis with lated at the MP2 and B3LYP levels. These dipole diuse functions having lower exponents to: 2i) moments will guide us as to the ability to bind an make our electronic energies consistent with those excess electron. With this goal in mind, the vertical that we are presently calculating for the corre- electron attachment energies are determined at sponding anionic species, and 2ii) estimate prop- Koopmans' theorem 2KT) level. An unexpected erly the vertical electron attachment energies at outcome of the current study on the six low energy Koopmans' theorem level [23]. Thus, we centered tautomers of arginine is that the largest dipole even-tempered [24] ®ve-term s and ®ve-term p sets moment of ca. 9 D is displayed by the lowest en- of diuse functions on the positive end of the ergy zwitterion's structure and by one of the non- molecular dipole of each species. This was either ionic structures. However, their vertical electron the C atom surrounded by three nitrogen atoms or detachment energies, determined at the KT level, one of the N atoms belonging to the ±C2NH2)2 2or dier considerably. C2NH)NH2) functional group. The extra diuse s and p functions share exponent values, the geo- metric progression ratio was equal to 5.0, and we 2. Methods started to build up the exponents from the lowest sp exponent included in the 6-31++G2d,p) basis set The equilibrium geometries of the neutral spe- designed for nitrogen. As a consequence, we cies have been optimized at the second-order achieved lowest exponents of 2:0448 Â 10À5 a.u.