J. Chem. Theory Comput. 2005, 1, 1055-1062
1055
Theoretical Study of the Interaction between the Guanidinium Cation and Chloride and Sulfate Anions Isabel Rozas* and Paul E. Kruger Centre for Synthesis and Chemical Biology, Department of Chemistry, Trinity College Dublin, Dublin 2, Ireland Received January 14, 2005
Abstract: The interactions between the guanidinium cation and the chloride and sulfate anions have been explored theoretically. As a basis for this study, the structure of the guanidinium cation has been reexamined and confirmed to possess a nonplanar propeller structure. Thus, computations at the MP2/6-31+G* level yielded several guanidinium-chloride complexes in 1:1 and 2:1 stoichiometry, with the most stable being those in which the guanidinium cation(s) interact in pincerlike form with the spherical chloride anion. In the case of guanidinium-sulfate complexes, a large number of stable 1:1 dimers and 2:1 trimers were found at the same level of computation. The nature of all the interactions established has been analyzed by means of the AIMs and NBO approaches, and several correlations have been found between electron density at the bond critical points, hydrogen bond distances, and orbital interaction energies. The guanidinium moiety has been widely exploited as an anion receptor in supramolecular chemistry and bears relation to the arginine amino acid, which interacts with anionic substrates within proteins. Thus, the current study provides insight into the nature of the interactions involving the guanidinium cation within both abiotic and natural systems.
Introduction There is considerable current interest in the development of molecular and supramolecular systems that have the ability to bind, identify, and signal the presence of negatively charged ions.1 The motivation behind such studies is the recognition that anions enjoy an important role in biology, medicine, and the environment.2 In the field of molecular recognition, the guanidinium cation has proven to be an extremely effective motif (host) for binding anionic guests.3 Strong noncovalent interaction between this host and guest species is derived from ion pairing and H-bonding (HB) contributions, and these interactions have been shown to be particularly effective even in competitive solvent systems such as water.4 Several features allow the guanidinium group to effectively bind anions. First, a very high pKa value of around 12-13 allows it to remain protonated over a wide pH range, including physiological pH. Furthermore, its geometrical orientation allows it to align well with anionic * Corresponding author phone: (+353) 1 608 3731; fax: (+353)1 671 2826; e-mail:
[email protected].
10.1021/ct050009x CCC: $30.25
groups, leading to a strong interaction. The incorporation of the guanidinium moiety into abiotic receptors is also driven in part by the recognition that the guanidinium group, in the form of the arginine amino acid, plays a crucial role in directing the formation of higher order structures in proteins through hydrogen-bonding as well as being a component found within enzymatic catalytic domains that bind anionic substrates.5 With the above concepts in mind, and in an effort to better understand those empirical contributions that lead to anion binding to the guanidinium cation, we undertook a theoretical study of the binding of the prototypical anions chloride (mononegative, spherical) and sulfate (dinegative, tetrahedral) to guanidinium. This empirical study provides a theoretical basis that might allow for better guanidinium receptor design and an impetus for our own formative structural studies into anion driven supramolecular chemistry.6 Initial computational work focused on calculating the minimized structure of the guanidinium moiety itself. We then moved onto consider the interaction of chloride and sulfate anions with the guani© 2005 American Chemical Society
Published on Web 08/18/2005
1056 J. Chem. Theory Comput., Vol. 1, No. 5, 2005
dinium cation in 1:1 (dimer) and 2:1 (trimer) host-to-guest stoichiometry, as these are the stoichiometries most commonly found within abiotic host-guest systems. A systematic search of the Cambridge Structural Database was also conducted to corroborate the results found via computational methods. Results from this study are presented herein.
Methods The geometry of the monomers (guanidinium cation and anion species) and host:guest complexes (guanidinium:anion) have been initially fully optimized with the Gaussian 987 program using the hybrid Hartree-Fock (HF) density functional theory (DFT) B3LYP/6-31G* computational level.8 These structures have been used as the starting point for the optimization at the second-order Møller-Plesset perturbation method (MP2),9 with the 6-31+G* basis set.10 In the case of the guanidinium cation the MP2 method with the 6-31++G** basis set11 was also used for comparison purposes. The combination of DFT and MP2 methods has proven to be sufficient for an accurate description of HBs and is not computationally expensive. In the case of the dimers, the minimum nature of the complexes has been confirmed by frequency calculations at both the B3LYP/631G* and MP2/6-31G* levels, whereas the trimers frequency calculations have been performed at the B3LYP/6-31G* level. Considering that the B3LYP and MP2 geometries were almost identical, B3LYP frequencies are enough to identify the trimers as minima. The interaction energies have been calculated as the difference of the total energy of the complex and the sum of the isolated monomers. The interaction energies obtained in the majority of the cases were very high, and no basis set superposition error (BSSE) was calculated since, in those situations, such corrections should be irrelevant. The topological properties of the electron charge density have been studied using the atoms in molecules methodology (AIM) with the AIMPAC program package.12 The natural bond orbital analysis was used to determine the nature of the interactions in the formation of the host:guest complexes. These calculations were performed with the NBO code implemented in Gaussian-98.13 A search of the Cambridge Structural Database (CSD version 5.25 April 2004 Update)14 for complexes of the guanidinium cation and chloride or sulfate anions was conducted employing the following restrictions: H-atoms were located, no disorder and a refinement (R-factor) e 6.0%. All of the structures matching these criteria were examined manually and the following, deemed the most relevant to the current study, were fully analyzed and discussed in the text: guanidinium chloride (CSD refcode: GANIDC), guanidinium sulfate (CSD refcode: GUANSL01), and guanidinium bisulfate (CSD refcode: VETQIU).
Results and Discussion Guanidinium Cation. For many years it was assumed that Y-conjugated molecules such as guanidinium were planar. Frenking15 showed that guanidinium possesses a nonplanar minimum structure. In fact their calculations at the HF/631G* level predicted a planar form of the guanidinium cation,
Rozas and Kruger Table 1. Total Energy (ET, au), Difference in Energy (∆E, kcal mol-1), ZPE and Frequencies for the Guanidinium Cation (G+) Calculated at the B3LYP/6-31G*, MP2/ 6-31+G*, and MP2/6-31++G** Levels B3LYP/6-31G*
ET
∆E
imaginary frequencies
G+ nonplanar G+ planar
-205.7593033 -205.7588422
0.29
0 1
MP2/6-31+G*
ET
∆E
imaginary frequencies
G+ nonplanar G+ planar
-205.1307722 -205.1297416
0.65
0 1
MP2/6-31++G** G+ nonplanar G+ planar
ET
∆E
imaginary frequencies
-205.1861055 -205.1852451
0.54
0 3
whereas at the MP2/6-31G* level such a planar form showed one imaginary frequency. The energy minimum structure at the MP2/6-31G* level had D3 symmetry with the NH2 groups rotated by 15° and a difference in energy from the planar form of 0.4 kcal mol-1. To evaluate the interaction energy of the guanidinium-chloride and guanidinium-sulfate complexes and to analyze the behavior of DFT methods we have reinvestigated the nonplanarity of guanidinium at the B3LYP/ 6-31G*, MP2/6-31+G* and MP2/6-31++G** levels. In Table 1 the results obtained for the planar and nonplanar forms are presented. In all cases the nonplanar form was the minimum energy structure, whereas the planar structure showed one to three imaginary frequencies. The difference in energy obtained with respect to the planar form was 0.29, 0.65, and 0.54 kcal mol-1 at the B3LYP/6-31G*, MP2/631+G*, and MP2/6-31++G** levels, respectively. The good performance of the B3LYP/6-31G* method is noteworthy since the results obtained are very similar to those observed by Frenking at the MP2 level employing the same basis set (∆ET ) 0.4 kcal mol-1, and one negative frequency for the planar form).16 Frenking found that with inclusion of the ZPE corrections, the planar form was more stable than the nonplanar form by 0.2 kcal mol-1. At the three levels of computation employed within the current study similar results were obtained; however, ZPE corrections cannot be applied to structures that show imaginary frequencies, as these data would be meaningless. Regarding the equilibrium structures at the three levels of computation, guanidinium shows D3 symmetry with the NH2 groups rotated around the C-NH2 bond by 14.5°, 16.9°, and 16.2°, respectively. The C-N bond lengths obtained in each case were the same for the planar and nonplanar forms and are very similar at the three levels of computation (B3LYP/ 6-31G*: 1.337 Å, MP2/631+G*: 1.336 Å, and MP2/631++G**: 1.336 Å). As in the case reported by Frenking these C-N distances are in excellent agreement with experimental values derived from vibrational spectra and X-ray diffraction studies (1.33-1.35 Å).16 The nonplanar form of guanidinium may be viewed as a left- or right-handed propeller. We have followed the
Chloride and Sulfate Anions
J. Chem. Theory Comput., Vol. 1, No. 5, 2005 1057 Table 2. Hydrogen Bond Parameters within Guanidinium Chloride (GANIDC), Guanidinium Sulfate (GUANSL01), and Guanidinium Bisulfate (VETQIU) as Derived from the CSD14 D-H/Å
d(H‚‚‚A)/Å
d(D‚‚‚A)/Å
