Molecular Self‐Recognition: Rotational Spectra of the Dimeric 2‐Fluoroethanol Conformers

Fluoroalcohols show competitive formation of intra‐ and intermolecular hydrogen bonds, a property that may be crucial for the protein‐altering process in a fluoroalcohol/water solution. In this study, we examine the intra‐ and intermolecular interactions of 2‐fluoroethanol (FE) in its dimeric conformers by using rotational spectroscopy and ab initio calculations. Three pairs of homo‐ and heterochiral dimeric FE conformers are predicted to be local minima at the MP2/6‐311++G(d,p) level of theory. They are solely made of the slightly distorted most stable G+g?/G?g+ FE monomer units. Jet‐cooled rotational spectra of four out of the six predicted dimeric conformers were observed and unambiguously assigned for the first time. All four observed dimeric conformers have compact geometries in which the fluoromethyl group of the acceptor tilts towards the donor and ensures a large contact area. Experimentally, the insertion of the O? H group of one FE subunit into the intramolecular O? H???F bond of the other was found to lead to a higher stabilisation than the pure association through an intermolecular O? H???O? H link. The hetero‐ and homochiral combinations were observed to be preferred in the inserted and the associated dimeric conformers, respectively. The experimental rotational constants and the stability ordering are compared with the ab initio calculations at the MP2 level with the 6‐311++G(d,p) and aug‐cc‐pVTZ basis sets. The effects of fluorination and the competing inter‐ and intramolecular hydrogen bonds on the stability of the dimeric FE conformers are discussed.     

Observation of the pure rotational spectra of trans- and cis-HOCO

Pure rotational spectra of trans- and cis-HOCO have been observed by Fourier transform microwave spectroscopy and the millimeter-wave double resonance technique, where gas phase spectra of the cis-conformer were observed for the first time. These radicals were produced in a supersonic jet by discharging a mixture gas of CO and H(2)O diluted in Ar. The molecular constants including the fine and hyperfine constants have been precisely determined for both conformers. Deuterated analogs have also been observed. The determined r(0) structures agree with these of ab initio calculations. The Fermi contact constants show a difference of the unpaired electron densities on the protons between the two conformers. Intensity of the spectrum for cis-HOCO was compared with that of trans-HOCO, leading to a conclusion that both conformers were produced nearly equally in abundance under the present experimental conditions.     

Ab initio studies of the conformers and conformational distribution of gas‐phase N,N‐dimethylaminopropanol

Systematic and extensive conformational search has been performed to characterize the gas‐phase N,N‐dimethylaminopropanol structures. A total of 91 unique trail structures were generated by allowing for all the single‐bond rotamers. All the trial structures were initially optimized at the AM1 level, and the resulting structures were optimized at the B3LYP/6‐311G* level of theory and then subjected to further optimization at the B3LYP/6‐311++G**. A total of 36 conformers are found and their zero‐point vibrational enegies, rotational constants, and dipole moments are determined. Vertical ionization energies of 11 low‐lying conformers predicted with the electron propagator theory are in good agreement with the experimental data. The two most stable conformers display intramolecular H bonds (HBs): OH···N. These HBs influence on the molecular electronic structures is exhibited by natural bond orbital analyses. Combined with statistical mechanics principles, conformational distributions at various temperatures are computed and the temperature dependence of photoelectron spectra is interpreted. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2010     

Conformational energetics of 1,3-dichloropropane as predicted by several calculations methods

Two semiempirical methods (MNDO and AM1), a molecular mechanics technique (MM2) and two ab initio approaches (6–31G* full optimization and 3–21G/6–31G*) were used to calculate the ordering of and energy difference between conformers in 1,3-dichloropropane. The semiempirical methods did not order the conformers properly or predict correct energy differences. Both ab initio methods ordered the conformers and predicted energy differences correctly, with the 6–31G* full optimization performing slightly better. The MM2 results were presented for calculations involving a force field with no hydrogens and a full force field of all atoms. The full force field properly ordered the conformers but did not correctly predict the energy differences. The nonhydrogen field ordered the conformers based on the Cl…Cl nonbonded distance. The data show that conformer stability is not a simple matter of maximizing the Cl…Cl nonbonded distance, but is also related to some other stabilizing interaction(s).     

The Structure and Torsional Dynamics of Two Methyl Groups in 2‐Acetyl‐5‐methylfuran as Observed by Microwave Spectroscopy

The molecular‐beam Fourier transform microwave spectrum of 2‐acetyl‐5‐methylfuran is recorded in the frequency range 2–26.5 GHz. Quantum chemical calculations calculate two conformers with trans or cis configuration of the acetyl group, both of which are assigned in the experimental spectrum. All rotational transitions split into quintets due to the internal rotations of two nonequivalent methyl groups. By using the program XIAM, the experimental spectra can be simulated with standard deviations within the measurement accuracy, and yield well‐determined rotational and internal rotation parameters, inter alia the V₃ potentials. Whereas the V₃ barrier height of the ring‐methyl rotor does not change for the two conformers, that of the acetyl‐methyl rotor differs by about 100 cm^?1. The predicted values from quantum chemistry are only on the correct order of magnitude.     

An exploration of conformational search of leucine molecule and their vibrational spectra in gas phase using ab initio methods

An extensive exploration of the conformational space has been carried out to characterize all possible gas phase structures of leucine. A total of 324 unique trial structures for canonical leucine were generated by considering all possible combinations of single bond rotamers. All trial structures were optimized at the B3LYP/6-311G* level of the DFT method. A total of 77 unique and stationary canonical conformers were found. Further, 15 most stable conformers were reoptimized at B3LYP/6-311++G** level and their respective relative energies, vertical ionization energies, hydrogen bonding patterns, rotational constants and dipole moments were calculated. A single point energy calculations for leucine conformers have also been done at both B3LYP/6-311++G(2df, p) and MP2/6-311++G(2df, p) levels. The good agreement between our estimates of rotational constants for two most stable conformers and available experimental measurements supports the reliability of the B3LYP/6-311++G** level of theory for describing the conformational behavior of leucine molecule. The proton affinity and gas phase basicity were also determined. Using the statistical approach, conformational distributions at various temperatures have also been performed and analyzed. Vibrational spectra were also calculated. It is also observed that zwitterions of leucine are not stable in gas phase.     

High resolution spectra and conformational analysis of 2-butoxy radical

We have recorded five high resolution (200 MHz), rotationally resolved, vibrational bands of the B-X electronic transition of 2-butoxy. Two bands of the 2-butoxy spectrum have been rotationally analyzed and assigned to two different geometrical conformers of the molecule. The analyses allow the determination of the six experimental rotational constants defined by the geometry of the species in the ground (X) and excited (B) electronic states and also four spin-rotation constants for the X electronic state of the conformers. Comparison of the experimental rotational constants with the results of ab initio computations provides unambiguous conformational assignment of these bands. This approach can be extended to assign two other spectral bands to the third 2-butoxy conformer.     

Discovering the Elusive Global Minimum in a Ternary Chiral Cluster: Rotational Spectra of Propylene Oxide Trimer

The chirality controlled conformational landscape of the trimer of propylene oxide (PO), a prototypical chiral molecule, was investigated using rotational spectroscopy and a range of theoretical tools for conformational searches and for evaluating vibrational contributions to effective structures. Two sets of homochiral (PO)₃ rotational transitions were assigned and the associated conformers identified with theoretical support. One set of heterochiral (PO)₃ transitions was assigned, but no structures generated by one of the latest, advanced conformational search codes could account for them. With the aid of a Python program, the carbon atom backbone and then the heterochiral (PO)₃ structure were generated using ¹³C isotopic data. Excellent agreement between theoretical and experimental rotational constants and relative dipole moment components of all three conformers was achieved, especially after applying vibrational corrections to the rotational constants.     

Conformational Studies of Methyl Vinyl Silane from Temperature-Dependent FT–IR Spectra of Xenon and Krypton Solutions

Variable-temperature (–55 to –155°C) studies of the infrared spectra (3500–400 cm^–1) of methyl vinyl silane, CH₂CHSiH₂CH₃, dissolved in liquid xenon and krypton have been recorded. Utilizing three sets of conformer doublets due to the cis and gauche rotamers, the enthalpy difference has been determined to be 133 ± 11 cm^–1 (1.59 ± 0.13 kJ/mol) with the gauche conformer the more stable form in the krypton solution. In the xenon solution, the enthalpy difference could not be determined because the infrared bands become so broad and the overlap was so extensive that meaningful areas could not be determined. Ab initio calculations have been carried out with several different basis sets up to MP2/6-311+G(2d,2p) from which structural parameters and conformational stabilities have been determined. With the largest basis set, the cis conformer is predicted to be the more stable conformer, which is inconsistent with the experimental results. Utilizing previously reported microwave rotational constants for both conformers along with the ab initio predicted distances and angles, r ₀ parameters have been obtained for both the cis and gauche conformers. The spectroscopic and theoretical results are compared to the corresponding quantities for some similar molecules.     

The singular gas-phase structure of 1-aminocyclopropanecarboxylic acid (Ac3c)

The natural nonproteinogenic α-amino acid 1-aminocyclopropanecarboxylic acid (Ac(3)c) has been vaporized by laser ablation and studied in the gas phase by molecular-beam Fourier transform microwave spectroscopy. Comparison of the experimental rotational and (14)N nuclear quadrupole coupling constants with the values predicted ab initio for these parameters has allowed the unambiguous identification of three Ac(3)c conformers differing in the hydrogen bonding pattern. Two of them resemble those characterized before for the coded aliphatic α-amino acids. Remarkably, a third conformer predicted to be energetically accessible for all of these amino acids but never observed (the so-called "missing conformer") has been found for Ac(3)c, close in energy to the global minimum. This is the first time that such a conformer, stabilized by an N-H···O(H) hydrogen bond, is detected in the rotational spectrum of a gaseous α-amino acid with a nonpolar side chain. The conjugative interaction established between the cyclopropane ring and the adjacent carbonyl group seems to be responsible for the unique conformational properties exhibited by Ac(3)c.     

Conformational stability from variable temperature infrared spectra of krypton solutions, ab initio calculations, vibrational assignment, and r0 structural parameters of 1,3-difluoropropane

The infrared spectra (3200-400 cm(-1)) of krypton solutions of 1,3-difluoropropane, FCH2CH2CH2F, at variable temperatures (-105 to -150 degrees C) have been recorded. Additionally, the infrared spectra (3200-50 cm(-1)) of the gas and solid have been recorded as well as the Raman spectrum of the liquid. From a comparison of the spectra of the fluid phases with that in the solid, all of the fundamental vibrations of the C2 conformer (gauche-gauche) where the first gauche indicates the form for one of the CH2F groups and the second gauche the other CH2F, and many of those for the C1 form (trans-gauche) have been identified. Tentative assignments have been made for a few of the fundamentals of the other two conformers, i.e. C2v (trans-trans) and Cs (gauche-gauche'). By utilizing six pairs of fundamentals for these two conformers in the krypton solutions, an enthalpy difference of 277 +/- 28 cm(-1) (3.31 +/- 0.33 kJ mol(-1)) has been obtained for the C2 versus C1 conformer with the C2 conformer the more stable form. For the C2v conformer, the enthalpy difference has been determined to be 716 +/- 72 cm(-1) (8.57 +/- 0.86 kJ mol(-1)) and for the Cs form 971 +/- 115 cm(-1) (11.6 +/- 1.4 kJ mol(-1)). It is estimated that there is 64 +/- 3% of the C2 form, 34 +/-3% of the C1 form, 1% of the C2v form and 0.6% of the Cs conformer present at ambient temperature. Equilibrium geometries and total energies of the four stable conformers have been determined from ab initio calculations with full electron correlation by the perturbation method to second order as well as by hybrid density functional theory calculations with the B3LYP method using a number of basis sets. The MP2 calculations predict the C1 conformer stability to be slightly higher than the experimentally determined value whereas for the C2v and Cs conformers the predicted energy difference is much larger than the experimental value. The B3LYP calculations predict a better energy difference for both the C1 and C2v as well as for the Cs conformers than the MP2 values. A complete vibrational assignment is proposed for the C2 conformer and many of the fundamentals have been identified for the C1 form based on the force constants, relative intensities and rotational-vibrational band contours obtained from the predicted equilibrium geometry parameters. By combining previously reported rotational constants for the C2 and C1 conformers with ab initio MP2/6-311 + G(d, p) predicted parameters, adjusted r0 parameters have been obtained for both conformers. Comparisons are made with the parameters obtained for some other molecules containing the FCH2 group. The spectroscopic and theoretical results are compared to the corresponding properties for some similar molecules.     

Conformation and configuration of tertiary amines via GIAO-derived (13)C NMR chemical shifts and a multiple independent variable regression analysis.

The (13)C chemical shifts of six tertiary amines of unambiguous conformational structure are compared to predicted (13)C NMR chemical shifts obtained via empirically scaled GIAO shieldings for geometries from MM3 molecular mechanics calculations. An average deviation, absolute value of Deltadelta(av), of 0.8 ppm and a maximum deviation, absolute value of Deltadelta(max), of 2.8 ppm between predicted and experimental (13)C shifts of the six tertiary amines of unambiguous structure are found. In several cases of tertiary amines subject to rapid exchange, where experimental (13)C shifts at room temperature are weighted averages of multiple conformers, a comparison of calculated (13)C shifts of all reasonable MM3 predicted conformers with experimental (13)C shifts via a multiple independent variable regression analysis provides an efficient method of determining the major and minor conformers. The examples presented are 2-methyl-2-azabicyclo[2.2.1]heptane and 1,6-diazabicyclo[4.3.1]decane, which each have two expected contributing structures, and 2-(diethylamino)propane and 1,8-diazabicyclo[6.3.1]dodecane, where ten and seven low-energy conformers, respectively, are predicted by MM3 calculations.     

Local Structures and Chemical Properties of Deprotonated Arginine

The potential energy surface of gaseous deprotonated arginine has been systematically in- vestigated by first principles calculations. At the B3LYP/6-31G(d) level, apart from the identification of several stable local structures, a new global minimum is located which is about 6.56 kJ/mol more stable than what has been reported. The deprotonated arginine molecule has two distinct forms with the deprotonation at the carboxylate group (COO^-). These two forms are bridged by a very high energy barrier and possess very different IR spectral profiles. Our calculated proton dissociation energy and gas-phase acidity of argi-nine molecule are found to be in good agreement with the corresponding experimental results. The predicted geometries, dipole moments, rotational constants, vertical ionization energies and IR spectra of low energy conformers will be useful for future experimental measurements.     

The Shape of the Simplest Non-proteinogenic Amino Acid α-Aminoisobutyric Acid (Aib)

The simplest non-proteinogenic amino acid α-aminoisobutyric acid (Aib), an analogue of glycine and alanine, has been vaporized by laser ablation and probed by high-resolution Fourier transform microwave spectroscopic techniques. Comparison of the experimental rotational and ¹⁴N nuclear quadrupole constants with that predicted ab initio has allowed the identification of three conformers of Aib exhibiting three types of hydrogen-bond interactions I (NH⋅⋅⋅O=C, cis-COOH), II (OH⋅⋅⋅N, trans-COOH), and III (N−H⋅⋅⋅O−H, cis-COOH) within the amino acid backbone. The observation of conformer III, not detected previously for related proteinogenic amino acids with a nonpolar side chain in a supersonic expansion, indicates that the presence of the methyl groups should restrict the conformational relaxation from conformer Aib-III to Aib-I. For conformer Aib-II, the rotational spectra of the ¹³C isotopomers reveal a tunneling motion arising from the two equivalent methyl groups in the molecule. The observation of a single spectrum at the midpoint between those predicted for the two ¹³C of the methyl groups has been explained by considering a double-minimum potential function with a low-energy interconversion barrier for a large amplitude internal motion. This singular fact has been corroborated by the anomalous centrifugal distortion effects determined in conformer Aib-II.     

Searching for conformers of nine- to twelve-ring hydrocarbons on the MM2 and MM3 energy surfaces: Stochastic search for interconversion pathways

The stochastic search method was employed to find as many conformers on the MM2 and MM3 energy surfaces as possible for cyclic saturated hydrocarbons with ring sizes from 9 through 12. The number found was 8 MM2 (8 MM3) for 9 rings, 18 MM2 (16 MM3) for 10 rings, 40 MM2 (29 MM3) for 11 rings, and 111 MM2 (90 MM3) for 12 rings. A measure of similarity between pairs of conformers of a compound, called conformational distance, is described. It was used to correlate similar MM2 and MM3 conformers. It was discovered that some conformers on each energy surface are not close to minima on the other surface in rings larger than 9. On refinement with the other optimizer, they changed considerably—going downhill to other previously found minima on the other energy surface or (in a few cases) going to minima which had not been found by direct searches. Conformational distance was also employed as an indication of which pairs of MM2 (or MM3) conformers are likely to interconvert rapidly. A new stochastic procedure of using small kicks was used to search for the most likely interconversion processes among the conformers. There is fairly good agreement between the most facile pathways located by it and unusually short conformational distances. Several additional 12-ring conformers (not found with previous methods) were located through application of this small kick procedure.     

Gas phase conformational behavior of selenomethionine: A computational elucidation

Selenium containing amino acids are known to play numerous key biological roles in various lifesupporting processes. In the current theoretical investigation DFT(B3LYP) and MP2 methods are used to study the gas phase conformers of the selenomethionine molecule in view of their relative stabilities, theoretically predicted harmonic frequencies, HOMO-LUMO energy gaps, rotational constants, and dipole moments. The number and type of intramolecular H-bond interactions existing in the selenomethionine conformers, which play key roles in determining the energy of the conformers, are also analyzed. The predicted geometries as well as the relative stabilities of the conformers suggest that the structural aspects and energies of the conformers may depend on the level of theory and the size of the basis set used. A comparison of the vibrational frequencies furnished in this study with the previous experimental and theoretical results obtained at MP2/6-31++G(d,p) and B3LYP/6-311++G(d,p) levels promotes the interpretation of the vibrational spectroscopy data on biologically relevant molecules.     

Detailed ab initio studies of the conformers and conformational distributions of gaseous tryptophan

A systematic and extensive conformational search has been performed to characterize the gas-phase tryptophan structures. A total of 648 unique trial structures were generated by allowing for all combinations of internal single-bond rotamers and were optimized at the DFT/B3LYP/6-311G* level of theory. A total of 45 local minima conformers were found. Further optimization of the 45 conformers with B3LYP and MP2/6-311++G** did not produce meaningful structural change, and accurate geometries, dipole moments, rotational constants, harmonic frequencies, and relative energies were then determined. Combined with statistical mechanics principles, the conformational distributions of gas-phase tryptophan at different temperatures are shown. The results clearly support the conclusion drawn by Compagnon et al. that only one dominant isomer existed in the molecular beam at 85 K and add further evidence that the supersonic jet expansion or embedding helium droplets did not produce an equilibrium distribution.     

A theoretical study of 1-amino-3-butene and 3-butene-1-thiol

Conformational analysis of 1-amino-3-butene and 3-butene-1-thiol was carried out using the 4-21G basis set. The conformers obtained were subjected to 6-31G^* single-point analysis for the calculation of energies, charge distributions, and dipole moments. The geometries and stabilities obtained are in good agreement with available experimental data. The results are interpreted in terms of intramolecular hydrogen bonding and anomeric interactions: Some of the most stable conformers of both molecules have intramolecular hydrogen bonds between the hydrogens of the amino or thiol groups and the electrons of the double bond. The 4-21G geometries were refined to obtain rotational constants closer to the experimental values.     

Molecular mechanics calculations of conjugated amides and an ab initio investigation of acrylamide and its β-amino derivative: Conformational analysis and rotational barriers

Conformations and rotational barriers in a series of conjugated primary and tertiary amides have been analyzed by a modified MM2(91) force field, which treats the amide nitrogen as part of the conjugated system by redefining the atom type for the nitrogen. Ab initio molecular orbital calculations at the MP2/6-31G* level have been performed on the stable conformers and transition structures of acrylamide and β-trans-aminoacrylamide. The results have been used, with published experimental and computational data, to generate parameters for the MM2 force field. The force field has been applied to various conjugated amides, such as reduced nicotinamide adenine dinucleotide (NADH) and NAD⁺ analogues, nicotinamide, urea, vinylogous urea derivatives, and nucleic acid bases. The fundamental difference between primary and tertiary conjugated amides with respect to both conformation and barrier is highlighted. © 1996 by John Wiley & Sons, Inc.