Structures and hydration enthalpies of cationized glutamine and structural analogues in the gas phase

The structures of lithiated and sodiated glutamine, both with and without a water molecule, are investigated using experiment and theory. Loss of water from these complexes and from lithiated and sodiated complexes of asparagine methyl ester, asparagine ethyl ester, and glutamine methyl ester is probed with blackbody infrared radiative dissociation experiments performed over a wide temperature range. Threshold dissociation energies, E(o), for loss of a water molecule from these complexes are obtained from master equation modeling of these data. The values of E(o) are 63 +/- 1 and 53 +/- 1 kJ/mol for the lithiated and sodiated glutamine complexes, respectively. These values are similar to those for the nonzwitterionic model complexes and are in excellent agreement with calculated values. In contrast, water binding to the zwitterionic form is calculated to be significantly higher. These results indicate that glutamine in these lithiated and sodiated complexes with a water molecule are nonzwitterionic. Complexes with the asparagine side chain have slightly higher E(o) values than those with the glutamine side chain, a result consistent with more effective solvation of the metal ion due to the slightly longer side chain of glutamine. Calculations indicate that lithiated and sodiated glutamine are nonzwitterionic, with the metal ion interacting with the amine nitrogen and carbonyl oxygen from the amino acid backbone and the amide oxygen of the side chain. Addition of a water molecule does not affect the lowest-energy structure of lithiated glutamine, whereas, for sodiated glutamine, the lowest-energy zwitterionic and nonzwitterionic structures are essentially isoenergetic.     

Structures of cationized proline analogues: evidence for the zwitterionic form

The structures of lithiated and sodiated alpha-methyl-proline (alpha-Me-Pro) and structural isomers, both with and without a water molecule, are investigated using blackbody infrared radiative dissociation (BIRD) and density functional theory. From the BIRD kinetic data measured as a function of temperature, combined with master equation modeling of these data, threshold dissociation energies for the loss of a water molecule from these clusters are obtained. These energies are 77.5 +/- 0.5 and 53 +/- 1 kJ/mol for lithiated and sodiated alpha-Me-Pro, respectively. For the nonzwitterionic isomer, proline methyl ester, these values are 3.0-4.5 kJ/mol higher. These results provide compelling experimental evidence that alpha-Me-Pro is zwitterionic in these clusters. Theory at the temperature corrected B3LYP/6-311++G**//B3LYP/6-31++G** level indicates that the salt-bridge or zwitterionic forms of lithiated and sodiated alpha-Me-Pro are between 17 and 23 kJ/mol lower in energy than the nonzwitterionic or charge-solvated forms and that attachment of a single water molecule does not significantly change the structure or the relative energies of these clusters. The proton affinity of proline is 8 kJ/mol higher than that of alpha-Me-Pro, indicating that lithiated and sodiated singly hydrated proline should also be zwitterionic.     

Infrared spectroscopy of cationized lysine and epsilon-N-methyllysine in the gas phase: effects of alkali-metal ion size and proton affinity on zwitterion stability

The gas-phase structures of protonated and alkali-metal-cationized lysine (Lys) and epsilon-N-methyllysine (Lys(Me)) are investigated using infrared multiple photon dissociation (IRMPD) spectroscopy utilizing light generated by a free electron laser, in conjunction with ab initio calculations. IRMPD spectra of Lys.Li(+) and Lys.Na(+) are similar, but the spectrum for Lys.K(+) is different, indicating that the structure of lysine in these complexes depends on the metal ion size. The carbonyl stretch of a carboxylic acid group is clearly observed in each of these spectra, indicating that lysine is nonzwitterionic in these complexes. A detailed comparison of these spectra to those calculated for candidate low-energy structures indicates that the bonding motif for the metal ion changes from tricoordinated for Li and Na to dicoordinated for K, clearly revealing the increased importance of hydrogen-bonding relative to metal ion solvation with increasing metal ion size. Spectra for Lys(Me).M(+) show that Lys(Me), an analogue of lysine whose side chain contains a secondary amine, is nonzwitterionic with Li and zwitterionic with K and both forms are present for Na. The proton affinity of Lys(Me) is 16 kJ/mol higher than that of Lys; the higher proton affinity of a secondary amine can result in its preferential protonation and stabilization of the zwitterionic form.     

Binding energies of water to doubly hydrated cationized glutamine and structural analogues in the gas phase

The modes of metal-ion and water binding in doubly hydrated complexes of lithiated and sodiated glutamine (Gln) are probed using blackbody infrared radiative dissociation experiments and density functional theory calculations. Threshold dissociation energies, E0, for loss of a water molecule from these complexes are obtained from master-equation modeling of these data. The values of E0 are 36 +/- 1 and 38 +/- 2 kJ/mol for the lithiated and sodiated glutamine complexes, respectively, and are consistent with calculated water binding energies for the nonzwitterionic form of these complexes. Calculated water binding energies for the zwitterionic forms of these complexes are significantly higher. In contrast, calculations indicate that the zwitterionic form of Gln in these complexes is more stable than the nonzwitterionic form by 8 and 15 kJ/mol when lithiated and sodiated, respectively. Doubly hydrated lithiated and sodiated complexes of asparagine methyl ester (AsnOMe), asparagine ethyl ester (AsnOEt), and glutamine methyl ester (GlnOMe) were also studied for comparison to Gln. Although these clusters lack the acidic group of Gln and therefore have different water coordination behavior, these results further support the conclusion that Gln is nonzwitterionic in these clusters. Surprisingly, the complexes containing sodium are more stable than those containing lithium, a result that is attributed to subtle differences in how these two metal ions bind to the amino acid esters in these complexes.     

One water molecule stabilizes the cationized arginine zwitterion

Singly hydrated clusters of lithiated arginine, sodiated arginine, and lithiated arginine methyl ester are investigated using infrared action spectroscopy and computational chemistry. Whereas unsolvated lithiated arginine is nonzwitterionic, these results provide compelling evidence that attachment of a single water molecule to this ion makes the zwitterionic form of arginine, in which the side chain is protonated, more stable. The experimental spectra of lithiated and sodiated arginine with one water molecule are very similar and contain spectral signatures for protonated side chains, whereas those of lithiated arginine and singly hydrated lithiated arginine methyl ester are different and contain spectral signatures for neutral side chains. Calculations at the B3LYP/6-31++G** level of theory indicate that solvating lithiated arginine with a single water molecule preferentially stabilizes the zwitterionic forms of this ion by 25-32 kJ/mol and two essentially isoenergetic zwitterionic structure are most stable. In these structures, the metal ion either coordinates with the N-terminal amino group and an oxygen atom of the carboxylate group (NO coordinated) or with both oxygen atoms of the carboxylate group (OO coordinated). In contrast, the OO-coordinated zwitterionic structure of sodiated arginine, both with and without a water molecule, is clearly lowest in energy for both ions. Hydration of the metal ion in these clusters weakens the interactions between the metal ion and the amino acid, whereas hydrogen-bond strengths are largely unaffected. Thus, hydration preferentially stabilizes the zwitterionic structures, all of which contain strong hydrogen bonds. Metal ion size strongly affects the relative propensity for these ions to form NO or OO coordinated structures and results in different zwitterionic structures for lithiated and sodiated arginine clusters containing one water molecule.     

Alkali metal ion binding to glutamine and glutamine derivatives investigated by infrared action spectroscopy and theory

The gas-phase structures of alkali-metal cationized glutamine are investigated by using both infrared multiple photon dissociation (IRMPD) action spectroscopy, utilizing light generated by a free electron laser, and theory. The IRMPD spectra contain many similarities that are most consistent with glutamine adopting nonzwitterionic forms in all ions, but differences in the spectra indicate that the specific nonzwitterionic forms adopted depend on metal-ion identity. For ions containing small alkali metals, the metal ion is solvated predominantly by the amino group, the carbonyl oxygen of the carboxylic acid group, and the carbonyl oxygen of the amide group. With increasing alkali-metal-ion size, additional structures are present in which the carboxylic acid group donates a hydrogen bond to the amino group and the metal ion is solvated only by the amide and carboxylic acid groups. The effects of alkylation of the amino and amide groups on the proton affinity of isolated glutamine and the relative zwitterion stability of sodiated glutamine were examined computationally. Methylation of the amino group increases the proton affinity of isolated glutamine and preferentially stabilizes the zwitterionic form of sodiated glutamine by roughly 20 kJ/mol. Ethylation and isopropylation of the amide group each increase the proton affinity of isolated glutamine by roughly 13 kJ/mol but preferentially stabilize the zwitterionic form of sodiated glutamine by less than 3 kJ/mol. These results indicate that effects of proton affinity on relative zwitterion stability compete with effects of metal-ion solvation.     

A semi-empirical and ab initio combined approach for the full conformational searches of gaseous lysine and lysine–H2O complex

A full structural search of the canonical, zwitterionic, protonated and deprotonated lysine conformers in gas phase is presented. A total of 17,496 canonical, 972 zwitterionic, 11,664 protonated and 1458 trial deprotonated structures were generated by allowing for all combinations of internal single-bond rotamers. All the trial structures were initially optimized at the AM1 level, and the resulting structures were determined at the B3LYP/6-311G^* level. A total of 927 canonical, 730 protonated and 193 deprotonated conformers were found, but there were no stable zwitterionic structures in the gas phase. The most stable conformers of the canonical, protonated and deprotonated lysine were further optimized at the B3LYP/6-311++G^** level. The energies of the most stable structures were determined at the MP2/6-311G(2df,p) level and the vibrational frequencies were calculated at the B3LYP/6-311++G^** level. The rotational constants, dipole moments, zero-point vibrational energies, harmonic frequencies, vertical ionization energies, enthalpies, Gibbs free energies and conformational distributions of gaseous lysine were presented. Numerous new structures are found and the lowest-energy lysine conformer is more stable than the existing one by 1.1 kcal/mol. Hydrogen bonds are classified and may cause significant red-shifts to the associated vibrational frequencies. The calculated proton affinity/dissociation energy and gas-phase basicity/acidity are in good agreement with the experiments. Calculations are also presented for the canonical lysine–H₂O and zwitterionic lysine–H₂O clusters. Interaction between lysine and H₂O significantly affects the relative conformational stabilities. Only one water molecule is sufficient to produce the stable zwitterionic structures in gas phase. The lowest-energy structure is found to be zwitterions when applying the conductor-like polarized continuum solvent model (CPCM) to the lysine–H₂O complexes.     

A theoretical investigation of the relative stability of hydrated glycine and methylcarbamic acid--from water clusters to interstellar ices

We have theoretically investigated how the low-energy conformers of the neutral and the zwitterionic forms of glycine as well as methylcarbamic acid are stabilized by the presence water. The MP2/6-311++G(d,p) method was utilized to conduct calculations on glycine and methylcarbamic acid in both isolated clusters and in clusters embedded in the conductor-like polarizable continuum model (C-PCM), where the clusters explicitly contain between one and ten water molecules. The neutral forms of glycine and methylcarbamic acid were found to have similar hydration energies, whereas the neutral methylcarbamic acid was determined to be approximately 32 kJ mol(-1) more stable than the neutral glycine in the isolated clusters and 30 kJ mol(-1) more stable in the C-PCM embedded clusters. Both the number and strength of the hydrogen bonding interactions between water and the zwitterions drive the stability. This lowers the relative energy of the glycine zwitterion from 50 kJ mol(-1) above neutral glycine, when there are two water molecules in the clusters to 11 kJ mol(-1) below for the clusters containing ten water molecules. For the methylcarbamic acid clusters with two water molecules, the zwitterion is 51 kJ mol(-1) higher in energy than the neutral form, but it remains 13 kJ mol(-1) above the neutral methylcarbamic acid in the clusters containing ten water molecules. When the bulk water environment is simulated by the C-PCM calculations, we find both the methylcarbamic acid and glycine zwitterionic forms have similar energies at 20 kJ mol(-1) above the neutral methylcarbamic acid energy and 10 kJ mol(-1) lower than the neutral glycine energy. Although neither methylcarbamic acid nor glycine have been detected in the interstellar medium yet, our findings indicate that methylcarbamic acid is the more stable product from methylamine and carbon dioxide reactions in a water ice. This suggests that methylcarbamic acid likely plays a role in the intermediate steps if glycine is formed in the interstellar medium.     

Effects of microsolvation and aqueous solvation on the tautomers of histidine: a computational study on energy, structure and IR spectrum

Microsolvation and combined microsolvation-continuum approaches are employed to investigate the structures and energies of canonical and zwitterionic histidine conformers. The effect of hydration on the relative conformational stability is examined. The strategy of exploring singly and doubly hydrated structures and the possible microsolvation patterns are described. We find that bonding water molecule may significantly change the relative conformational stabilities. In gas phase, the singly and doubly hydrated canonical forms are more stable than their zwitterionic counterparts. In solution, the continuum solvent model shows that bare zwitterionic form is more stable than bare canonical form by 1.1 kcal/mol. This energy separation is increased to 2.2 and 3.4 kcal/mol with inclusion of one and two explicit water molecules, respectively. We have also observed that the doubly hydrated structures obtained by combining two water molecules simultaneously to the solute molecule are preferred over the stepwise hydration. Hydrogen bond energies for the most stable hydrated histidine tautomers are determined by the atoms in molecules theory. The infrared (IR) spectra for the most stable singly and doubly hydrated structures of both histidine tautomers in gas phase are characterized. The stretching frequencies for NH of imidazole ring and OH of COOH are red shifted due to the hydrations. The IR spectra for the most stable zwitterionic tautomers in solution are also presented and discussed in connection with the comparison to the experiments. The pKa values obtained for the ring protonated zwitterions with two explicit water molecules appear to be in good agreement with the experiments.     

Arginine zwitterion is more stable than the canonical form when solvated by a water molecule

We present calculations for the Arg-H2O system and predict that the zwitterionic Arg is thermodynamically more stable than the canonical form in the gas phase under the influence of a single water molecule because of the strongly basic guanidine side chain. Canonical conformers of Arg-H2O are found to isomerize to the zwitterionic forms via a small barrier (approximately 6 kcal/mol).     

Low-energy tautomers and conformers of neutral and protonated arginine.

The relative stabilities of zwitterionic and canonical forms of neutral arginine and of its protonated derivative were studied by using ab initio electronic structure methods. Trial structures were first identified at the PM3 level of theory with use of a genetic algorithm to systematically vary geometrical parameters. Further geometry optimizations of these structures were performed at the MP2 and B3LYP levels of theory with basis sets of the 6-31++G** quality. The final energies were determined at the CCSD/6-31++G** level and corrected for thermal effects determined at the B3LYP level. Two new nonzwitterionic structures of the neutral were identified, and one of them is the lowest energy structure found so far. The five lowest energy structures of neutral arginine are all nonzwitterionic in nature and are clustered within a narrow energy range of 2.3 kcal/mol. The lowest energy zwitterion structure is less stable than the lowest nonzwitterion structure by 4.0 kcal/mol. For no level of theory is a zwitterion structure suggested to be the global minimum. The calculated proton affinity of 256.3 kcal/mol and gas-phase basicity of 247.8 kcal/mol of arginine are in reasonable agreement with the measured values of 251.2 and 240.6 kcal/mol, respectively. The calculated vibrational characteristics of the low-energy structures of neutral arginine provide an alternative interpretation of the IR-CRLAS spectrum (Chapo et al. J. Am. Chem. Soc. 1998, 120, 12956-12957).     

Ab initio molecular dynamics free-energy study of microhydration effects on the neutral-zwitterion equilibrium of phenylalanine.

The structures and relative energies of the most stable conformers of both naked and microsolvated phenylalanine, Phe.(H(2)O)(n)(n=0-3), are calculated by density functional theory. For selected structures, coordination-constrained ab initio molecular dynamics simulations determine the proton-transfer mechanism connecting neutral and zwitterionic forms of Phe. The associated free-energy profiles are calculated by thermodynamic integration. While no zwitterionic free-energy minimum is found for naked Phe, microsolvation is found to stabilize the zwitterionic form. For cluster sizes n > or = 3, the proton-transfer equilibrium shifts towards the zwitterionic structure for specific proton-transfer pathways. The energetically most favourable interconversion path between the neutral and zwitterionic forms is through a H(2)O bridge with free-energy barriers as low as 14.4 kJ mol(-1) for Phe.(H(2)O)(3). The free energy required for breaking a carboxylic OH bond involved in intramolecular hydrogen bonding is typically lower than in the water-assisted case. However, the resulting zwitterion turns out to be unstable with respect to the backward proton-transfer reaction.     

Effect of metal ion and water coordination on the structure of a gas-phase amino acid.

The mode of metal ion and water binding to the amino acid valine is investigated using both theory and experiment. Computations indicate that without water, the structure of valine is nonzwitterionic. Both Li(+) and Na(+) are coordinated to the nitrogen and carbonyl oxygen (NO coordination), whereas K(+) coordinates to both oxygens (OO coordination) of nonzwitterionic valine. The addition of a single water molecule does not significantly affect the relative energies calculated for the cationized valine clusters. Experimentally, the rates of water evaporation from clusters of Val.M(+)(H(2)O)(1), M = Li, Na, and K, are measured using blackbody infrared radiative dissociation. The dissociation rate from the valine complex is compared to water evaporation rates from model complexes of known structure. These results indicate that the metal ion in the lithiated and the sodiated clusters is NO-coordinated to nonzwitterionic valine, while that in the potassiated cluster has OO coordination, in full agreement with theory. The zwitterionic vs nonzwitterionic character of valine in the potassiated cluster cannot be distinguished experimentally. Extensive modeling provides strong support for the validity of inferring structural information from the kinetic data.     

Conformational search for zwitterionic leucine and hydrated conformers of both the canonical and zwitterionic leucine using the DFT-CPCM model

The stable conformations for zwitterionic leucine have been searched for in solution as well as in gas phase. A total of 54 trial structures were generated by considering possible combinations of single bond rotamers. It is observed that zwitterions are not stable in gas phase. In order to investigate the zwitterions of leucine in solution, the calculations for all trial structures of zwitterions were performed initially at the PM3 level and 14 the lowest energy structures were reoptimized at the B3LYP/6-311G(d) level using the CPCM model. Seven of these conformers of zwitterionic leucine were found to be stable in solution. The five most stable conformers were then reoptimized at the B3LYP/6-311++G(d, p) level. The energy ordering of the canonical leucine(neutral) conformers were also considered on the basis of single point energy calculations at the B3LYP/6-311++G(d, p) level using the CPCM model. The chemical hardness, chemical potential, vertical ionization energy and vertical electron affinity were calculated for a few of the most stable canonical leucine and its zwitterions in solution. The effects of explicit addition of water molecules (microsolvation) on the structure and the energy of both canonical and zwitterionic conformers of leucine were investigated. It is noted that in gas phase, the singly and doubly hydrated canonical (neutral) forms are more stable than their zwitterionic counterparts. The solvated zwitterions and canonical structures of leucine were further investigated using the discrete/SCRF model with zero, one and two water molecules. In solution, the continuum solvent model shows that the bare zwitterionic form is more stable than the bare canonical form by 1.6 kcal/mol. This energy separation is increased to 3.8 and 4.8 kcal/mol with inclusion of one and two water molecules, respectively. The optimized structural parameters for the most stable zwitterionic leucine with zero, one and two water molecules in solution were compared with those reported for l-leucine crystal, which shows a close agreement between the optimized geometrical parameters of the zwitterionic leucine with two water molecules in solution with the experimental geometrical parameters for l-leucine crystal. It is also observed that when the structures of zwitterions with one and two explicit water molecules are optimized in solution, the geometrical parameters and their relative energies are found to be appreciably modified. We have also calculated the vibrational spectra of the most stable solvated zwitterionic leucine as well as for the most stable structure of zwitterionic leucine with one and two water molecules in solution.     

Chair, boat and twist conformation of dodecamethylcyclohexasilane and undecamethylcyclohexasilane: a combined DFT and Raman spectroscopic study.

The conformations of dodecamethylcyclohexasilane Si6Me12 and undecamethylcyclohexasilane Si6Me11H have been investigated by ab initio calculations employing the B3LYP density functional with a 6-31+G(d) basis set. Local minima as well as transition structures were calculated with imposed symmetry constraints. For Si6Me12, three unique minima, which correspond to the chair, twist and boat conformations were located with relative zero-point-vibration-corrected energies of 0.0, 7.8 and 11.4 kJ mol(-1). A half-chair conformation with four coplanar silicon atoms connects the chair and twisted minima via an energy barrier of 16.0 and 8.2 kJ mol(-1), respectively. A second transition structure with a barrier of 3.9/0.3 kJ mol(-1) connects the twist with the boat structure. Solution Raman spectra of Si6(CH3)12 and Si6(CD3)12 fully corroborate these results. Below -40 degrees C, the symmetric SiSi ring breathing vibration is a single line, which develops a shoulder (originating from the twist conformer) at longer wavelengths whose intensity increases with increasing temperature. From a Van't Hoff plot, the chair/twist enthalpy difference is 6.6+/-1.5 kJ mol(-1) for Si6(CH3)12 and 6.0+/-1.5 kJ mol(-1) for Si6(CD3)12, which is in reasonable agreement with the ab initio results. Due to the low barrier, the boat conformation cannot be observed, because either the lowest torsional vibration level lies above it or a rapid interconversion between the twist and boat conformations occurs, resulting in averaged Raman spectra. For Si6Me11H, six local minima were located. The chair with the hydrogen atom in the axial position (axial chair) is the global minimum, followed by the equatorial chair (+1.9 kJ mol(-1)) and the three twist conformers (+5.3, +8.0 and +8.1 kJ mol(-1)). The highest local minimum (+11.9 kJ mol(-1)) is a C(s) symmetric boat with the hydrogen atom in the equatorial position. Two possible pathways for the chair-to-chair interconversion with barriers of 13.9 and 14.5 kJ mol(-1) have been investigated. The solution Raman spectra in the SiSi ring breathing region clearly show that below -50 degrees C only the axial and equatorial chairs are present, with an experimental deltaH-value of 0.46 kJ mol(-1). With increasing temperature a shoulder develops which is attributed to the combined twist conformers. The experimental deltaH-value is 6.9 kJ mol(-1), in good agreement with the ab initio results. Due to the low interconversion barriers, the various twist conformers cannot be detected separately.     

Binding energies of water to sodiated valine and structural isomers in the gas phase: the effect of proton affinity on zwitterion stability

The structures of valine (Val) and methylaminoisobutyric acid (Maiba) bound to a sodium ion, both with and without a water molecule, are investigated using both theory and experiment. Calculations indicate that, without water, sodiated Val forms a charge-solvated structure in which the sodium ion coordinates to the nitrogen and the carbonyl oxygen (NO-coordination), whereas Maiba forms a salt-bridge structure in which the sodium ion coordinates to both carboxylate oxygens (OO-coordination). The addition of a single water molecule does not significantly affect the relative energies or structures of the charge-solvated and salt-bridge forms of either cluster, although in Maiba the mode of sodium ion binding is changed slightly by the water molecule. The preference of Maiba to adopt a zwitterionic form in these complexes is consistent with its higher proton affinity. Experimentally, the rates of water evaporation from clusters of Val.Na(+)(H(2)O) and Maiba.Na(+)(H(2)O) are measured using blackbody infrared radiative dissociation (BIRD). The dissociation rates from the Val and Maiba complexes are compared to water evaporation rates from model complexes of known structure over a wide range of temperatures. Master equation modeling of the BIRD kinetic data yields a threshold dissociation energy for the loss of water from sodiated valine of 15.9 +/- 0.2 kcal/mol and an energy of 15.1 +/- 0.3 kcal/mol for the loss of water from sodiated Maiba. The threshold dissociation energy of water for Val.Na(+)(H(2)O) is the same as that for the charge-solvated model isomers, while the salt-bridge model complex has the same water threshold dissociation energy as Maiba.Na(+)(H(2)O). These results indicate that the threshold dissociation energy for loss of a water molecule from these salt-bridge complexes is approximately 1 kcal/mol less than that for loss of water from the charge-solvated complexes.     

Theoretical study of the gas-phase structures of sodiated and cesiated leucine and isoleucine: zwitterionic structure disfavored in kinetic method experiments

The most stable charge-solvated (CS) and zwitterionic (ZW) structures of sodiated and cesiated leucine and isoleucine were studied by density functional theory methods. According to the Boltzmann distribution in gas phase, both forms of LeuNa+ and IleNa+ exist, but in LeuCs+ and IleCs+, the ZW forms are dominant. Results for the sodiated compounds are consistent with the relationship found between decrease in relative stability of CS versus ZW form and aliphatic amino acid side chain length. The observed degeneracy in energy for IleNa+ conformers is at odds with kinetic method results. Additional calculations showed that kinetic method structural determinations for IleNa+ do not reflect relative order of populations in the lowest energy conformers. Since complexation of cationized amino acids into ion-bound dimers disfavors ZW structure by approximately 8 kJ mol(-1), it is suggested that for energy close conformers of sodium-cationized amino acids, the kinetic method may not be reliable for structural determinations.     

Infrared spectroscopy of cationized arginine in the gas phase: direct evidence for the transition from nonzwitterionic to zwitterionic structure

The gas-phase structures of protonated and alkali metal cationized arginine (Arg) and arginine methyl ester (ArgOMe) are investigated with infrared spectroscopy and ab initio calculations. Infrared spectra, measured in the hydrogen-stretch region, provide compelling evidence that arginine changes from its nonzwitterionic to zwitterionic form with increasing metal ion size, with the transition in structure occurring between lithium and sodium. For sodiated arginine, evidence for both forms is obtained from spectral deconvolution, although the zwitterionic form is predominant. Comparisons of the photodissociation spectra with spectra calculated for low-energy candidate structures provide additional insights into the detailed structures of these ions. Arg*Li+, ArgOMe*Li+, and ArgOMe*Na+ exist in nonzwitterionic forms in which the metal ion is tricoordinated with the amino acid, whereas Arg*Na+ and Arg*K+ predominately exist in a zwitterionic form where the protonated side chain donates one hydrogen bond to the N terminus of the amino acid and the metal ion is bicoordinated with the carboxylate group. Arg*H+ and ArgOMe*H+ have protonated side chains that form the same interaction with the N terminus as zwitterionic, alkali metal cationized arginine, yet both are unambiguously determined to be nonzwitterionic. Calculations indicate that for clusters with protonated side chains, structures with two strong hydrogen bonds are lowest in energy, in disagreement with these experimental results. This study provides new detailed structural assignments and interpretations of previously observed fragmentation patterns for these ions.     

Structure, stability, and interconversion barriers of the rotamers of cis-[Pt(II)Cl(2)(quinoline)2] and cis-[Pt(II)Cl(2)(3-bromoquinoline)(quinoline)] from X-ray crystallography, NMR spectroscopy and molecular mechanics evidence

Reported are the preparations of cis-[PtCl(2)(quinoline)(2)] and cis-[PtCl(2)(3-bromoquinoline)(quinoline)] and an investigation of the stabilities and interconversion of the rotamer forms of these complexes. Both head-to-head (HTH) and head-to-tail (HTT) rotamer forms are found in the crystal structure of cis-[PtCl(2)(quinoline)(2)]. The NOESY NMR spectrum of cis-[PtCl(2)(quinoline)(2)] in dmf-d(7) at 300 K is consistent with conformational exchange brought about by rotation about the Pt-N(quinoline) bonds. H.H nonbonded distances between H atoms of the two different quinoline ligands were determined from NOESY data, and these distances are in accord with those observed in the crystal structure and derived from molecular mechanics models. cis-[PtCl(2)(3-bromoquinoline)(quinoline)] was prepared to alleviate the symmetry-imposed absence of inter-ring H2/H2 and H8/H8 NOESY cross-peaks for cis-[PtCl(2)(quinoline)(2)]. Molecular mechanics calculations on the complexes show the HTT rotamers to be 1-2 kJ mol(-)(1) more stable than the HTH forms, consistent with the (1)H spectra where the intensities of resonances for the two forms are approximately equal. Variable-temperature (1)H NMR spectra of cis-[PtCl(2)(quinoline)(2)] in dmf-d(7) indicate a rotational energy barrier of 82 +/- 4 kJ mol(-)(1). Variable-temperature (1)H NMR spectra indicate that the Br substituent on the quinoline ring does not affect the energy barrier to interconversion between the HTT and HTH forms (79 +/- 5 kJ mol(-)(1)). The steric contribution to the rotation barrier was calculated using molecular mechanics calculations and was found to be approximately 40 kJ mol(-)(1), pointing to a possible need for an electronic component to be included in future models.     

Effects of alkaline earth metal ion complexation on amino acid zwitterion stability: results from infrared action spectroscopy

The structures of isolated alkaline earth metal cationized amino acids are investigated using infrared multiple photon dissociation (IRMPD) spectroscopy and theory. These results indicate that arginine, glutamine, proline, serine, and valine all adopt zwitterionic structures when complexed with divalent barium. The IRMPD spectra for these ions exhibit bands assigned to carboxylate stretching modes, spectral signatures for zwitterionic amino acids, and lack bands attributable to the carbonyl stretch of a carboxylic acid functional group. Structural and spectral assignments are strengthened through comparisons with absorbance spectra calculated for low-energy structures and the IRMPD spectra of analogous ions containing monovalent alkali metals. Many bands are significantly red-shifted from the corresponding bands for amino acids complexed with monovalent metal ions, owing to increased charge transfer to divalent metal ions. The IRMPD spectra of arginine complexed with divalent strontium and barium are very similar and indicate that arginine adopts a zwitterionic form in both ions. Calculations indicate that nonzwitterionic forms of arginine are lowest in free energy in complexes with smaller alkaline earth metal cations and that zwitterionic forms are preferentially stabilized with increasing metal ion size. B3LYP and MP2 calculations indicate that zwitterionic forms of arginine are lowest in free energy for M = Ca, Sr, and Ba.