Conformational landscape of l-threonine in neutral,acid and basic solutions from vibrational circular dichroism spectroscopy and quantum chemical calculations

The biological relevance of amino acids is well known. They can be used as zwitterionic, cationic or anionic forms according to the pH of the medium where they are. Thus, our aim herein was to study the conformational preference of the polar amino acid l-threonine [C₄H₉NO₃, (2S,3R)-2-amino-3-hydroxybutyric acid] under different pH conditions. A conformational study in an aqueous solution of the dissociation equilibrium of the amino acid l-threonine was carried out for this purpose. We recorded, at room temperature, the Mid-IR, Far-IR, Raman and VCD spectra of l-threonine from the aqueous solutions at pH values 5.70 (zwitterionic species), 1.00 (protonated species) and 13.00 (deprotonated species). The number of conformers found with the conformational search was 9 zwitterions, 27 anions and 52 cations. Both the study of the conformational landscape and the theoretical analysis of the vibrational features were accomplished by using DFT and ab initio calculations, that is, B3LYP/6-311++G(d,p) level of theory for all the conformers obtained from the conformational search, M062X/6-311++G(d,p) and MP2/6-311++G(d,p) levels of theory for the most stable conformers. The presence of water was included with the IEF-PCM implicit hydration model. With regard to the zwitterion, the importance of the analysis of the low frequency region (700–30 cm^–1) in the Far-IR spectra should be noted, because it provides relevant information that can be used to determine the presence of the most stable structures.     

Conformational isomerism of 1-butene secondary ozonide as studied by means of matrix isolation infrared absorption spectroscopy

Theoretical calculations of structures, stability and vibrational spectra of 1-butene secondary ozonide (SOZ) conformers were performed using DFT method B3LYP with a 6-311++G(3df, 3pd) basis set. The calculations predict six staggered structures of 1-butene SOZ. The FTIR spectra of 1-butene SOZ isolated in Ar, N₂ and Xe matrices were recorded. It was found that nitrogen is the best suited for the matrix isolation of 1-butene SOZ. The bandwidth of the spectral bands of the ozonide isolated in nitrogen was as narrow as 2 cm⁻¹. For the first time the existence of five conformers of 1-butene SOZ were confirmed experimentally by means of matrix isolation infrared absorption spectroscopy. The equatorial gauche (∠OCCC=−66.1°) conformer was proved theoretically and experimentally to be the most stable. It was found that due to high potential barriers of the conformational transitions annealing of the matrix is useless for the assignment of spectral bands to various conformers of 1-butene SOZ. Using the hot nozzle technique the van’t Hoff experimental plots were made for three additional conformers of 1-butene SOZ and experimental ΔH values for these additional conformers were established. The crystallization problems of 1-butene SOZ are discussed which accounts for the rich conformational diversity of the ozonide as well as high conformational barriers for axial-equatorial transitions.      

35Cl NQR Spectra and ab initio Calculations of gem-Substituted 1-Chlorocyclohexane Derivatives

The ³⁵Cl NQR spectra of gem-substiutted 1-chlorocyclohexane derivatives C₆H₁₀XCl (X = H, CH₃, CH₃O, Cl) at 77 K were measured. Ab initio RHF/6-31G(d) calculations of their conformers, and also of conformers of monosubstituted cyclohexanes were performed. Based on the calculation results, the NQR lines were assigned and the conformational energies of the substituents were evaluated. The relative conformational energies of the Cl atom and CH₃O group disagree with previous data.     

Vibrational spectra,conformational equilibria,ab initio calculations and vibrational assignments of ethylmethylfluorosilane

The infrared spectra of ethylmethylfluorosilane (CH₃SiHFCH₂CH₃) have been recorded as a vapour, liquid and solid at 78 K in the 4000–50 cm⁻¹ range and isolated in an argon matrix at ca. 5 K. Infrared spectra of two different solid phases were obtained after annealing to temperatures of 120 and 130 K, and recooling to 78 K. Although the IR spectra were quite similar in the MIR region, certain differences were noted in the FIR region below 400 cm⁻¹. The most stable conformer MeMe was present after annealing to 130 K, but three bands belonging to MeH were detected after annealing to 120 K. Various infrared bands changed intensity when the argon matrix was annealed to temperatures between 20 and 35 K, and some of these were related to changes in the conformational abundance.Raman spectra of the liquid were recorded at room temperature and at various temperatures between 295 and 153 K. Spectra of an amorphous and annealed solid were recorded at 78 K. In the variable temperature Raman spectra, various bands changed in intensity and were interpreted in terms of conformational equilibria between the three possible conformers. Complete assignments were made for all the bands of the most stable conformer MeMe. From various bands assigned to the three conformers, the conformational enthalpy difference ΔH from MeMe to the intermediate energy conformer MeH was found to be 0.5 kJ mol⁻¹ and to the highest conformer MeF was 0.7 kJ mol⁻¹. At ambient temperature this leads to 39% MeMe, 32% MeH and 29% of the MeF conformer in the liquid.Ab initio calculations in the RHF, MP2, DFT approximations and very accurate G2 calculations were carried out. With one exception, the MeMe conformer had the lowest enthalpy in all these calculations, the MeH had the intermediate and the MeF the highest enthalpy, and the calculations were in good agreement with the measurements.     

Vibrational Circular Dichroism Spectroscopy of Three Multidentate Nitrogen Donor Ligands: Conformational Flexibility and Solvent Effects

A series of multidentate nitrogen donor ligands have been synthesized and characterized and their conformational distributions in solution have been investigated. Vibrational absorption (VA) and vibrational circular dichroism (VCD) spectroscopy, complemented with DFT calculations, have been used to probe the conformations of these important ligands in solution directly. These three ligands demonstrate very different conformational flexibility; the pyridine subunits and amine groups may adopt a number of different conformations. Experimental VA and VCD data measured in CDCl₃ have been compared to the theoretical spectra of all possible most stable conformers. Solvent effects have been taken into account by using the implicit polarizable continuum model and explicit solvation model. The explicit hydrogen‐bonding solvation model is important for explaining the VCD sign‐reverse phenomenon in the amide I region. Good agreement has been achieved between experimental and predicted spectra for all three ligands; thus allowing detailed examination of the related conformational structures and distributions in solution.     

Ground-state conformational equilibrium of previtamin D and its E-isomer: Effect on the absorption characteristics

The ground-state conformational analysis of previtamin D, its E-isomer, tachysterol, their 10-desmethyl analogues and 1-methyl-1-hydroxy-previtamins have been performed by force-field calculations. Differences in the absorption characteristics of these compounds are discussed in view of the chromophore geometry and abundance (%) of the calculated conformers according to a Boltzmann distribution at 298 K. On the basis of present calculations, the red shift of previtamin D low-temperature UV and CD spectra determined earlier is attributed to the shift of conformational equilibrium in favour of more stable cZc geometries. The effect of complex formation with simplest model cluster of silica surface ((H₃SiO)₃SiOH), on previtamin D and tachysterol conformational equilibria and on UV-absorbance maxima has been evaluated.     

Matrix isolation FT-IR spectroscopy and molecular orbital study of sarcosine methyl ester

N-methylglycine methyl ester (sarcosine-Me) has been studied by matrix isolation FT-IR spectroscopy and molecular orbital calculations undertaken at the DFT/B3LYP and MP2 levels of theory with the 6-311++G(d,p) and 6-31++G(d,p) basis set, respectively. Twelve different conformers were located in the potential energy surface of the studied compound, with the ASC conformer being the ground conformational state. This form is analogous to the dimethylglycine methyl ester most stable conformer and is characterized by a NH?O intramolecular hydrogen bond; in this form, the ester group assumes the cis configuration and the OC-C-N and Lp-N-C-C (where Lp is the nitrogen lone electron pair) dihedral angles are ca. −17.8 and 171.3°, respectively. The second most stable conformer (GSC) differs from the ASC conformer essentially in the conformation assumed by the methylamino group, which in this case is gauche (Lp-N-C-C dihedral angle equal to 79.4°). On the other hand, the third most stable conformer (AAC) differs from the most stable form in the conformation of the OC-C-N axis (151.4°). These three forms were predicted to differ in energy by less than ca. 5 kJ mol⁻¹ and represent ≈95% of the total conformational population at room temperature. FT-IR spectra were obtained for sarcosine-Me isolated in argon matrices revealing the presence in the matrices of the three lowest energy conformers predicted by the calculations. The matrices were prepared by deposition of the vapour of the compound using two different nozzle temperatures, 25 and 60 °C. The relative populations of the three conformers trapped in the matrices were found to be consistent with occurrence of conformational cooling during matrix deposition and with a stabilization of the most polar GSC and AAC conformers in the matrices compared to the gas phase. Indeed, like it was previously observed for the methyl ester of dimethylglycine [Phys. Chem. Chem. Phys. 5 (2003) 52] the different strength of the interactions between the conformers and the matrix environment seem to lead to a change in the relative order of stabilities of GSC and ASC upon going from the gas phase to the matrices, with the first conformer becoming the conformational ground state in the latter media. The assignment of the bands observed in the matrix spectra to the three experimentally observed conformers of sarcosine-Me is presented and discussed.     

Raman spectra,conformational stability,structural parameters,vibrational assignment,and ab initio calculations for epifluorohydrin

The Raman spectra (3200–100 cm⁻¹) of epifluorohydrin, OCH₂CH(CH₂F), in variable solvents, as well as that of the gas have been recorded and several of the bands due to the two less stable conformers have been identified. The variable solvent studies were inconclusive on the relative conformer stabilities. The conformational energy differences and optimized geometries for all three conformers have been obtained from ab initio calculations with the 3–21G, 4–31G and 6–31G* basis sets. A normal coordinate analysis has also been performed for each conformer with a force field determined from the 3–21G basis set. Assignment of the vibrational fundamentals observed in the Raman spectra of the fluid phases is proposed based on the normal coordinate calculations. In the liquid phase, one of the conformers with a large dipole moment predominates and it appears to be the gauche-I form which is the only one found in the solid. Utilizing the three rotational constants previously reported for each conformer, along with restricted relative distances for several of the structural parameters among the conformers from ab initio calculations, r₀ structural parameters for the heavy atoms have been determined.     

Double resonance spectroscopy of different conformers of the neurotransmitter amphetamine and its clusters with water

In this paper the conformational landscape of amphetamine in the neutral ground state is examined by both spectroscopy and theory. Several spectroscopic methods are used: laser-induced fluorescence (LIF), resonance-enhanced two-photon ionization (R2PI), dispersed fluorescence and IR/R2PI hole burning spectroscopy. The latter two methods provide for the first time vibrationally resolved spectra of the neutral ground state of dl-amphetamine and the amphetamine–(H₂O)_1,2 complexes. Nine stable conformers of the monomer were found by DFT (B3LYP/6-311++G(d,p)) and ab initio (MP2/6-311++G(d,p)) calculations. For conformer analysis the vibrations observed in the IR/R2PI hole burning and dispersed fluorescence spectra obtained from single vibronic levels (SVLF) of a selected conformer were compared with the results of an ab initio normal mode analysis. By this procedure three S₀ → S₁ transitions in the R2PI spectrum were assigned to three different conformer structures. Another weak transition earlier attributed to another conformer could be assigned to a vibronic band of one of the three conformers. Furthermore spectra of amphetamine–(H₂O)_1,2 are tentatively assigned.     

Solvent Effects on IR Modes of (R)-3-Methylcyclopentanone Conformers: A Computational Investigation

Density Functional Theory (DFT) calculations of infrared spectra for the optimized geometries of the R-(+)-3-methylcyclopentanone (R3MCP) equatorial-methyl and axial-methyl conformers were performed in eleven common solvents with a wide polarity range, within the framework of polarizable continuum model (PCM). The DFT correlation function type B3LYP, using a powerful basis set (aug-cc-pVDZ), yielded different linear correlations between solvent polarity and R3MCP equatorial and axial conformers for frequencies of IR modes, intensities, and enthalpies. DFT calculations of the dipole moments of R3MCP equatorial and axial conformer components in 3D were also carried out and found to have a linear correlation with the solvent polarity. An increasing trend for the hypsochromic (blue) shift in the equatorial conformer??s IR frequencies is observed, in comparison to bathochromic (red) shift for the axial-methyl conformer IR modes, as a function of the solvent polarity.     

Solvated potential energy surfaces for MePC

A conformational study of methylphosphocholine (MePC) was performed from a conformational map calculated considering the dihedral angles that most affected the energy of the system. This conformational map was obtained from interpolations of energy values found from calculations that took into account the presence of solvent through a dielectric continuum approach. We used a quantum–mechanical method based on the Density Functional Theory (DFT) and the 6-31G(d,p) basis set. Conformational samplings were performed in stability regions and the most stable conformers were identified. Comparisons of samplings in solvated and non-solvated conformational maps were performed, and although very different from each other, they furnish equivalent final conformational sets. Both the sets reproduced satisfactorily the experimental shift observed for the vibrational modes of –[P(O₂)]⁻– and –CH₂– methylene groups of MePC when the system was solvated.     

Full MP2 study of solvent implicit and explicit effect on tautomers of Dithio-Biuret

Dithio biuret conformers were optimised and frequency calculations were performed at MP2/6–311++G(d,p) level of theory. Classification of conformers was done to five different tautomers and the most stable conformer of each tautomer was selected. Tautomer 3 having trans conformation of amino and thiocarbonyl functional group was the most stable tautomer in the gas phase. Optimisation and frequency calculations were also done in four different solvents as follows: benzene, acetonitrile, DMSO and water. Stability of tautomers were compared in these solvents to explore effect of polarity on stabilisation of tautomers. Inter-conversion of selected tautomers was investigated both in the gas phase and in four different media. Results showed that when solvent is used as an implicit media, it has negligible effect on proton transfer. Water-explicit effect was also investigated and the results exhibited high dependency of proton transfer mechanism on water molecules when they participate in breaking and formation of bonds.     

Structural Relevance of Intramolecular H-Bonding in Ortho-Hydroxyaryl Schiff Bases: The Case of 3-(5-bromo-2-hydroxybenzylideneamino) Phenol

A new Schiff base compound, 3-(5-bromo-2-hydroxybenzylideneamino)phenol (abbreviated as BHAP) was synthesized and characterized by ¹H- and ¹³C- nuclear magnetic resonance and infrared spectroscopies. DFT/B3LYP/6-311++G(d,p) calculations were undertaken in order to explore the conformational space of both the E- and Z- geometrical isomers of the enol-imine and keto-amine tautomers of the compound. Optimized geometries and relative energies were obtained, and it was shown that the most stable species is the E-enol-imine form, which may exist in four low-energy intramolecularly hydrogen-bonded forms (I, II, V, and VI) that are almost isoenergetic. These conformers were concluded to exist in the gas phase equilibrium with nearly equal populations. On the other hand, the infrared spectra of the compound isolated in a cryogenic argon matrix (10 K) are compatible with the presence in the matrix of only two of these conformers (conformers II and V), while conformers I and VI convert to these ones by quantum mechanical tunneling through the barrier associated with the rotation of the OH phenolic group around the C–O bond. The matrix isolation infrared spectrum was then assigned and interpreted with help of the DFT(B3LYP)/6-311++G(d,p) calculated infrared spectra for conformers II and V. In addition, natural bond orbital (NBO) analysis was performed on the most stable conformer of the experimentally relevant isomeric form (E-enol-imino conformer V) to shed light on details of its electronic structure. This investigation stresses the fundamental structural relevance of the O–H···N intramolecular H-bond in o-hydroxyaryl Schiff base compounds.     

Conformational equilibrium and potential energy surface of 1-fluorobutane by microwave spectroscopy and Ab initio calculations

The rotational spectra of four (GT, TT, TG, and GG) of the five possible conformers of 1-fluorobutane have been assigned by combining free jet and conventional microwave spectroscopy. The geometry optimization was performed at the MP2 (full) level of theory with the 6-31G (d) and 6-311G (d, p) basis sets and by using the B3LYP (3df, 3pd) density functional method. The relative stability of the five rotamers is calculated at the QCISD (T)/6-311G (d, p) level of theory. In spite of the fact that ab initio calculations indicated the unobserved GG' conformer to be more stable than at least one of the observed conformers it was not possible to detect its rotational spectrum. GT and TG are the most and the least stable species, respectively. The rotational spectra of several vibrational satellites of the four conformers have been studied by conventional microwave spectroscopy. The overall conformational equilibrium is governed by the two-dimensional potential energy surface of the skeletal torsions MeC-CC and FC-CC, which have been evaluated by a flexible model analysis, based on the experimental values of the relative conformational and vibrational energy spacings, and on the shifts of second moments of inertia upon conformational change and vibrational excitation. The relative energy of the fifth stable conformer (GG') was determined to be 333 cm(-1) from flexible model calculations, and to be 271 cm(-1) from the most accurate ab initio calculations.     

Simulated Raman spectra of four tetraphenylbutadiene polymorphs

We report a combined experimental and theoretical investigation on the Raman spectra of the polymorphs α, β, γ, and δ of 1,1,4,4‐tetraphenyl‐1,3‐butadiene (TPB), in the region of the intramolecular modes. The interpretation of the polarized spectra is supported by ab‐initio calculations for the isolated molecules and by lattice dynamics calculations for the crystals. The calculations reproduce the peculiar, and surprisingly large, differences among the spectra of the various polymorphs. The phenyl groups of 1,1,4,4‐tetraphenyl‐1,3‐butadiene may arrange themselves around the butadiene skeleton in 2 stable conformers, which have either inversion (C_i) or 2‐fold (C₂) symmetry and therefore exhibit intramolecular vibrations with quite different Raman selection rules and spectra. The compound forms 4 crystalline polymorphs (α, β, γ, and δ) with different combinations of C_i and C₂ conformers, and correspondingly different intramolecular spectra. The theoretical calculations provide a quantitative analysis of the various spectra.     

Thermodynamical properties of ε-caprolactone

The values of the combustion and enthalpies of formation for ε-caprolactone were determined by means of combustion calorimetry. The vapor pressures of lactone were measured in the range of 283–353 K, and the value of its enthalpy of vaporization was estimated by the transpiration method. Conformational analysis and calculations of the equilibrium structures, inertia moments, and sets of fundamental vibrations was performed by the B3LYP/6-311++G(3 df, 3 pd) quantum-chemical method. The total energies of the most stable lactone conformers were found and Δ_fH(g) was estimated using the composite G3MP2 method. The set of fundamental vibrations for the most stable conformers of the compound was developed on the basis of the available experimental IR spectra and calculated vibration frequencies. The values of the thermodynamic properties of ε-caprolactone were determined in the ideal ga s state in the range of 0—1500 K. A set of reliable and interconsistent thermodynamic parameters for ε-caprolactone was created. Thermodynamic analysis for liquid-phase polymerization of s-caprolactone in the temperature range of 220—500 K was carried out.     

Potential energy distributions and potential scans for the internal rotation of two rotors in 3,3-dichloro and 3,3,3-trichloropropanals.

The conformational behavior and structural stability of 3,3-dichloropropanal and 3,3,3-trichloropropanal were investigated by ab initio calculations. The 6-311 + + G** basis set was employed to include polarization and diffuse functions in the calculations at B3LYP level. From the calculation, the trans conformer of 3,3,3-trichloropropanal was predicted to be the predominant conformer with about 2 kcal mol(-1) of energy lower than the cis form. Additionally, 3,3 dichloro-propanal was predicted to exist as a mixture of three stable conformers. The potential function scans were calculated for the two molecules from which the rotational barriers could be estimated. The vibrational frequencies were computed at B3LYP level and complete vibrational assignments were made based on normal coordinate calculations for the conformers of the two molecules. Vibrational Raman and infrared spectra of the mixture of the stable conformers were computed at 300 K.     

Molecular conformations of a partially halogenated ether: A study based on infrared spectroscopy and density functional theory calculations

A new partially halogenated ether (ClCF₂CF(CF₃)OCF₂CH₃) has been synthesized and characterized using DSC, GC, ¹H and ¹⁹F NMR, IR. The experimental infrared spectra of this “flexible” molecule have been successfully interpreted on the basis of reliable Density Functional Theory calculations. An efficient method useful for the identification of the many stable conformers has been developed and applied. Infrared spectra of the stable conformers have been simulated after full geometry optimization. The results obtained allow detection of conformation-sensitive bands, making possible the interpretation of fine details in the spectra.     

Spectroscopic and theoretical investigation of (R)-3-methylcyclopentanone. The effect of solvent and temperature on the distribution of conformers

Temperature-dependent electronic circular dichroism (CD) spectra are reported for (R)-(+)-3-methylcyclopentanone (R3MCP) in 34 solvents. Analysis of these data yielded the enthalpy and entropy differences between axial methyl and equatorial methyl conformers, the dominant conformers for R3MCP. The weakly absorbing n-->pi* transition exhibited a decrease in lambdamax as the solvent polarity increased. Vibrational CD fine structure of the n-->pi* transition was observed in the gas phase in addition to several of the solvents. Vapor-phase CD spectra were compared to both the solution-phase spectra and theoretical calculations of the axial and equatorial methyl conformers. Optical rotation (OR) measurements for R3MCP in cyclohexane solution in the visible region showed excellent agreement with OR DFT calculations of the equatorial and axial methyl conformers. Density functional calculations with B3LYP and the 6-13G* and aug-cc-pVDZ basis sets, which incorporate the solvent dielectric constant, yielded trends in thermodynamic quantities as a function of polarity and solvent dipole moments that are only weakly or not observed in experiments.     

Vibrational Spectra, Assignment, Conformational Stability and Ab Initio/DFT Calculations for 1-Nitropropane

The infrared spectra (4000–400 cm^{– 1}) of solid and the Raman spectra (3500–30 cm^{– 1}) of liquid and solid 1-nitropropane, CH₃CH₂CH₂NO₂, have been registered. Both the trans and gauche conformers have been identified in the fluid phase, while the trans form remains in the stable solid. Temperature dependence (190–230K) of the liquid 1-nitropropane Raman spectra has been carried out. From these data, the enthalpy difference was determined to be 870 ± 105 J-mol^–1, with the gauche conformer being the more stable rotamer. Ab initio and DFT calculations at different levels of approximation (HF, MP2, B3LYP, B3PW91) gave optimized geometries, harmonic force fields, and vibrational frequencies for the trans and gauche conformers. All the calculations (except the B3PW91/6-31G* level) predicted gauche as the low-energy conformer. Theoretical force constants are analyzed for formulating constraints in the molecular force field model of 1-nitropropane.