PMC:4264129 / 179002-185611 JSONTXT

{"project":"2_test","denotations":[{"id":"25353178-22066681-52044543","span":{"begin":522,"end":524},"obj":"22066681"},{"id":"T66228","span":{"begin":522,"end":524},"obj":"22066681"}],"text":"3.4. 7-Member Rings\nWith increasing molecular size, a smaller and smaller number of papers were found, which would deal with the maintenance of the intramolecular H-bond in different phases. This is not surprising because of the increasing difficulties in interpreting the experimental results for molecules with a longer aliphatic chain, or the exponential increase of the conformations, which would enormously increase the computer time even using medium size basis sets. Earlier in this paper, results of Chen et al., [47] were referred to. The authors did not observe populations in the gas phase for 1,5-pentadiol conformations, which were stabilized by an intramolecular H-bond. Such a bond would involve formation of an eight-member ring. Thus this review ends here, where seven-member rings stabilized by a H-bond will be surveyed. Experimental gas-phase results have been found for γ-substituted carboxylic acids, although only for two of them.\n\nγ-OH and γ-NH2 Carboxylic Acids\nγ-OH butyric acid (GHB). The molecule is thermally unstable and converts to the cyclic butyrolactone structure by losing a water molecule. This feature makes the experimental investigation difficult. Regarding the gas-phase structure, only a conference abstract has been found by Suenram et al. [49]. By applying CP-FTMW (chirped pulse Fourier transform microwave) spectroscopy, the authors recorded the spectra of the α-, β-, and γ-OH butyric acids in order to study their conformational geometries and the effect of the internal H-bonding for the various compounds. The mixture for the γ-isomer did contain butyrolactone in the gas phase. The experimental results were compared with calculated MP2/6-311++G** + ZPE relative energies. For the γ-OH butyric acid, the attached slides give the impression that the molecule in its lowest-energy conformation forms an intramolecular H-bond between the alcohol OH and the carbonyl oxygen. The second lowest-energy conformer without an intramolecular H-bond is higher in energy by only 3 cm−1 (0.04 kJ/mol).\nNagy et al., [48] studied eight selected conformations for γ-OH butyric acid up to the MP2/6-311++G** level. The lowest energy conformer was found to form an O–H…O= internal bond. In the second stable structure this bond is disrupted and the energy is higher by about 1 kJ/mol, but the calculated free energy difference at T = 310 K is more than 2 kJ/mol in favor of the structure without the indicated internal bond. It must be mentioned, however, that the thermal corrections were calculated at the HF/6-31G* level, and even their relative values may be exaggerated.\nUsing the gas-phase optimized geometries, the relative solvation free energies in aqueous solution were predicted for the eight conformers throughout MC/FEP simulations. The total free energy differed by 1.3 kJ/mol for the lowest and second-lowest stability species with extended aliphatic chains for each. No intramolecular H-bond exists even in the third-lowest free energy conformation of ΔGtot = 2.3 kJ/mol. Thus, the water solvent disrupts the intramolecular H-bonds for γ-OH butyric acid and stabilizes extended conformations.\nThe solvent effect was studied in the same publication using mixed solvents of MeOH and CHCl3 in molar ratio of 2:1. The relative free energy is about 10 kJ/mol in favor of an extended structure in comparison with a nearly cyclic form prerequisite for the lactone formation. The calculated free energy difference is, however, relatively small as activation free energy for lactone formation in solution.\nγ-NH2 butyric acid (GABA). The gas-phase conformation was studied by Blanco et al., [50] using the LA-MB-FTMW technique. Five families including altogether nine conformations were observed in the experiment. Both fully extended conformations and those with NCCC gauche arrangement were identified. As mentioned, the two mostly populated species do not possess an intramolecular hydrogen bond.\nRamek and Nagy [238] studied the neutral/zwitterionic equilibrium of γ-NH2 butyric acid in aqueous solution. The total relative free energy was calculated as the sum of the internal free energy in the gas phase + relative solvation free energy. The zwitterion is not stable in the gas phase, thus its local-energy-minimum dihydrates were determined. For comparing the structures on equal footing, the dihydrates of the neutral conformers were optimized, as well. Among the isolated neutral species with geometries optimized in the dihydrate, the GABA structure without an intramolecular H-bond was found as the most stable conformation. The conformer with an intramolecular N…H–O–C=O bond was calculated to be higher in energy by 4.1 kJ/mol at the MP2/6-311++G**//HF/6-311++G** level.\nThe in-solution studies predicted the preference of each of the considered three zwitterionic forms relative to the neutral conformers. The most stable zwitterion had NCCC gauche and CCCC trans arrangements, thus the structure is fairly extended and exists without an intramolcular H-bond. Two cyclic zwitterionic conformers were investigated allowing for the formation of a –NH3+…−OCO bond. The extended form is more stable by at least 8.5 kJ/mol. No remarkable zwitterionic fraction was predicted, however, in slightly polar organic solvents such as chloroform and dicholoromethane. The partitioning between the aqueous and organic phases was predicted through the gradual shift of the zwitterionic to the neutral form in aqueous solution [239].\nCrittenden et al., [76] calculated the gas-phase conformational equilibrium and the relative stability of the neutral and zwitterionic GABA forms in solution. Ab initio (HF, MP2) and DFT (B3LYP) calculations using the 6-31G+* basis set were performed considering two and five explicit water molecules in a continuum dielectric solvent, modeled by COSMO. The most stable gas-phase structure out of nine studied conformers is an extended species without forming an intramolecular H-bond. In-solution studies proved the preference of the zwitteionic form, but if a pure solvent was placed into the cavity carved in the continuum water solvent, the preferred conformation for the zwitterion was a cyclic one with an intramolecular –NH3+…−OCO bond. No stable neutral GABA.2H2O structure was found, COSMO predicted different favorable zwitterionic structures. The extended structures are superior compared to the folded conformations. Both long-range and explicit water…GABA interactions preferentially stabilize the zwitterionic form. The authors allowed for the existence of a number of stable zwitterionic conformations in aqueous solution.\n"}