Theoretical Conformational Analysis Research Articles

Conformational analysis of 2-substituted nitroethenes

Experimental and theoretical conformational analysis of polyfunctional 2-substituted nitroethenes was carried out by the method of dipole moments and density functional theory calculations. It was established that the nitro and ester (or trichloromethyl) groups are trans-arranged in the molecules of 2-trichloromethyl-(ethoxycarbonyl)-1-nitro- and 1-bromo-1-nitroethenes, i.e., nitroalkenes have E-configuration, their bromo-containing analogues have Z-configuration, and s-cis-orientation of the C=C and C=O double bonds is preferred for nitroacrylates. 2,3-Dibromo-3-nitroacrylates have untrivial Z-configuration in solution.

ChemInform Abstract: Steric Perturbation of the Conjugated Triene Chromophore. Conformational Analysis of (E)- and (Z)-3-Methyl-1,3,5-hexatriene and ( Z)-3-tert-Butyl-1,3,5-hexatriene

A theoretical and NMR-spectroscopic conformational analysis is presented of the 3-methyl-1,3,5-hexatrienes and of (Z)-3-tert-butyl-1,3,5-hexatriene. It is shown that (E)-3-methyl-1,3,5-hexatriene exists mainly as the tEt rotamer and (Z)-3-methyl-1,3,5-hexatriene as the tZt rotamer. Indications are found for steric strain involving the Me group of the E isomer. In contrast to earlier theoretical predictions, this strain does not lead to detectable amounts of s-cis rotamers. Ab-initio calculations reported here agree with this experimental finding, but MMP2 calculations underestimate the energy of the s-cis form. 1H NMR relaxation rates and Nuclear Overhauser Enhancements (NOE) are shown to allow a reliable determination of the predominant ground-state conformation of alkyl-substituted hexatrienes. NOE experiments on (Z)-3-tert-butyl-1,3,5-hexatriene reveal that a tert-Bu group changes the preferred conformation from tZt to cZt but, surprisingly, is unable to completely counteract the strong intrinsic preference for a spatially extended s-trans,s-trans conformation. We estimate the rotamer population as cZt/tZt = 80/20 (±5).

Conformational Studies on Rotenoid and Its Biosynthetic Implications

The conformational studies for three rotenone isomers, using a simple rotenoids model has been analyzed by DFT method in B3LYP level of theory and 6-31G∗ basis set to obtain energy. This study shows how a systematic theoretical conformational analysis contributes to understanding molecular level of chemical processes. The gas phase structures are discussed based on thermodynamic values. The results supported that the biological effects of rotenone can be a consequence of conformational restriction and cis preference. The significance of these results is identifying the rotenone toxicity mechanism.

Experimental and theoretical conformation analysis of eight-membered silocines with planar fragments

The dipole moments of 6-thia-4,5: 6,7-dibenzo-1,3,2-dioxasilocines were determined experimentally and calculated at the DFT B3LYP/6-31G* level of theory and by the additivity scheme. The experimental and theoretical (DFT B3LYP/6-31G*) conformation analysis of eight-membered 1,3,2-dioxasilocines having planar fragments showed that these compounds in solution exist as boat-chair, boat-boat, or twist-boat conformers, depending on the presence of unsaturated planar fragment, nature of the heteroatom in position 6 of the eight-membered ring, and substituents on the silicon atom.

Theoretical conformational analysis of rutin

AbstractThe structural properties of rutin were determined by using a computational multistep progression. In the first step a stochastic strategy based on a molecular mechanics calculation was adopted to obtain a preliminary screening of the low-energy rutin conformations. The most stable structures obtained by the random conformational search were used as a starting point for an Austin Model 1 (AM1) semiempirical optimization. After this treatment, 16 structures characterized by a more stable frontal in respect to back disposition of the glycosidic chain of rutin were identified. To validate the results found from the stochastic search a molecular dynamics simulation was carried out. The results evidenced the presence of a global minimum highly stabilized by a hydrogen bond between the hydroxyl in the 3′ position of the B ring and the endocyclic oxygen of the rhamnose unit followed by approximately 8 kJ mol −1 less stable local minima with similar energy values. Finally, the reliability of the molecular model was confirmed by comparing the calculated electronic absorption spectrum with that measured on a methanolic rutin solution.Graphical abstract[IMAGE]

Crystal structure of the biclotymol–N,N-dimethylacetamide solvate 1:1: experimental and theoretical conformational analysis of biclotymol molecule

The crystal structure of the N,N-dimethylacetamide–biclotymol 1:1 solvate has been determined at room temperature by X-ray single-crystal diffraction. The molecular geometry of the biclotymol molecule is compared to the geometries observed in the N,N-dimethylformamide and dimethylsulfoxide solvates, and in the unsolvated form Phase-I. Rotational energy profile of the isolated molecule was obtained by semi-empirical AM1 calculations with respect to two selected torsional angles, which were rotated from 0° to 360° by steps of 10°. Not only, we find the two conformations experimentally observed, but also the conformation proposed by simple force fields calculations 30 years ago. Moreover, we propose three additional possible conformations that may offer potential candidates for the structure biclotymol Phase-II, which remains to be solved.

Tautomerism of the natural thymidine nucleoside and the antiviral analogue D4T. Structure and influence of an aqueous environment using MP2 and DFT methods

A comparative theoretical conformational analysis of the tautomerism of the four most stable conformers of the antiviral analogue D4T (stavudine) and natural thymidine (Thy) nucleosides was carried out, by using the B3LYP and MP2 quantum chemical methods. The calculated structure data and energy values of the tautomers were compared with the T1 keto form and with the results determined for the thymine molecule. For each conformer, only two stable enol forms, T3 and T5, were obtained when considering different positions of hydrogen around the base. Tautomer T3 always appears more stable than T5, and more stable in the natural nucleoside Thy than in thymine or in D4T.The effect of water on the tautomers was estimated by using an explicit number of up to five water molecules to surround the nucleoside, and also by Tomasi's polarized continuum model (PCM). A total of about 200 clusters were optimised and the geometrical parameters and energies discussed. The water net differs in the three tautomers of D4T and Thy. Depending on the nature of the tautomers, cyclic, distributed water molecules, or clustered structures are formed. The deformation and interaction counterpoise (CP)-corrected energies between the nucleoside and water molecules were determined. The relative stabilities of all tautomers were established. The microhydrated environment stabilizes remarkably the enol forms more than the canonical keto one, although this one continues being the most stable. The changes in the intramolecular H-bondings and in the total atomic charges were discussed. Intramolecular H-bonds being stronger in D4T than in Thy could indicate a higher molecular flexibility for Thy.

Experimental and Theoretical Conformational Analysis of 5‐Benzylimidazolidin‐4‐one Derivatives – a ‘Playground’ for Studying Dispersion Interactions and a ‘Windshield‐Wiper’ Effect in Organocatalysis

AbstractThe PF6 salts of 5‐benzyl‐1‐isopropylidene‐ and 5‐benzyl‐1‐cinnamylidene‐3‐methylimidazolidin‐4‐ones 1 (Scheme) with various substituents in the 2‐position have been prepared, and single crystals suitable for X‐ray structure determination have been obtained of 14 such compounds, i.e., 2–10 and 12–16 (Figs. 2–5). In nine of the structures, the Ph ring of the benzyl group resides above the heterocycle, in contact with the cis‐substituent at C(2) (staggered conformation A; Figs. 1–3); in three structures, the Ph ring lies above the iminium π‐plane (staggered conformation B; Figs. 1 and 4); in two structures, the benzylic CC bond has an eclipsing conformation (C; Figs. 1 and 5) which places the Ph ring simultaneously at a maximum distance with its neighbors, the CO group, the NC‐π‐system, and the cis‐substituent at C(2) of the heterocycle. It is suggested by a qualitative conformational analysis (Fig. 6) that the three staggered conformations of the benzylic CC bond are all subject to unfavorable steric interactions, so that the eclipsing conformation may be a kind of ‘escape’. State‐of‐the‐art quantum‐chemical methods, with large AO basic sets (near the limit) for the single‐point calculations, were used to compute the structures of seven of the 14 iminium ions, i.e., 3, 4/12, 5–7, 13, and 16 (Table) in the two staggered conformations, A and B, with the benzylic Ph group above the ring and above the iminium π‐system, respectively. In all cases, the more stable computed conformer (‘isolated‐molecule’ structure) corresponds to the one present in the crystal (overlay in Fig. 7). The energy differences are small (≤2 kcal/mol) which, together with the result of a potential‐curve calculation for the rotation around the benzylic CC bond of one of the structures, 16 (Fig. 8), suggests that the benzyl group is more or less freely rotating at ambident temperatures. The importance of intramolecular London dispersion (benzene ring in ‘contact’ with the cis‐substituent in conformation A) for DFT and other quantum‐chemical computations is demonstrated; the benzyl‐imidazolidinones 1 appear to be ideal systems for detecting dispersion contributions between a benzene ring and alkyl or aryl CH groups. Enylidene ions of the type studied herein are the reactive intermediates of enantioselective organocatalytic conjugate additions, Diels–Alder reactions, and many other transformations involving α,β‐unsaturated carbonyl compounds. Our experimental and theoretical results are discussed in view of the performance of 5‐benzyl‐imidazolidinones as enantioselective catalysts.

10.1007/s11176-008-2016-8

Theoretical conformational analysis of 1-nitro- and 1-bromo-1-nitro-2-(trichloromethyl)ethenes dissolved in methylene chloride and benzene was carried out by the B3LYP/6-31G* method. The calculated structures of these compounds were found to nicely fit experiment: Both in the gas phase and in solution, 1-nitro-(2-trichloromethyl)ethene is an E isomer, while its bromine-containing analog is a Z isomer.

Microwave measurements and ab initio calculations of structural and electronic properties of N-Et-1,2-azaborine

Rotational transitions for N-Et-1,2-azaborine were measured in the 5-13 GHz range using a Flygare-Balle type Fourier transform spectrometer system. Twelve distinct rotational transitions with over 130 resolved hyperfine components, which included a-dipole and b-dipole transitions, were measured and analyzed to obtain rotational constants and (11)B and (14)N nuclear quadrupole coupling constants in the principal rotational axis system. Rotational constants obtained are A=4477.987(4), B=1490.5083(7), and C=1230.6728(6) MHz. The quadrupole coupling constants for (11)B are eQq(aa)=-1.82(1), (eQq(bb)-eQq(cc))=-3.398(4) MHz, and for (14)N, eQq(aa)=1.25(1), (eQq(bb)-eQq(cc))=0.662(4) MHz. Quantum electronic structure calculations predict a ground-state structure with the ethyl group perpendicular to the azaborine plane and rotational constants in very good agreement with the measured structure and rotational constants. The theoretical conformational analysis of the ethyl group rotation around the N[Single Bond]C bond in relation to the heterocyclic ring yielded an asymmetric torsional potential energy surface with barrier heights of about 900 and 1350 cm(-1) for the N-Et-1,2-azaborine. Results of the measurements and calculations indicate that the basic molecular structure of N-Et-1,2-azaborine is similar to ethylbenzene. Electrostatic potential calculations qualitatively show that pi-electron density is somewhat delocalized around the 1,2-azaborine ring.

Theoretical and Experimental Studies on α/ε-Hybrid Peptides: Design of a 14/12-Helix from Peptides with Alternating (S)-C-Linked Carbo-ε-amino Acid [(S)-ε-Caa(x)] and l-Ala

An (S)-C-linked carbo-epsilon-amino acid [(S)-epsilon-Caa((x))] was prepared from the known (S)-delta-Caa. This monomer was utilized together with l-Ala to give novel alpha/epsilon-hybrid peptides in 1:1 alternation. Conformational analysis on penta- and hexapeptides by NMR (in CDCl(3)), CD, and MD studies led to the identification of robust 14/12-mixed helices. This is in agreement with the data from a theoretical conformational analysis on the basis of ab initio MO theory providing a complete overview on all formally possible hydrogen-bonded helix patterns of alpha/epsilon-hybrid peptides with 1:1 backbone alternation. The "new motif" of a mixed 14/12-helix was predicted as most stable in vacuum. Obviously, the formation of ordered secondary structures is also possible in peptide foldamers with amino acid constituents of considerable backbone lengths. Thus, alpha/epsilon-hybrid peptides expand the domain of foldamers and allow the introduction of desired functionalities via the alpha-amino acid constituents.

Theoretical conformational analysis of unsaturated phospines and phosphinechalcogenides

A theoretical conformational analysis was performed for vinylphosphine CH2=CHPH2 and three vinylphosphinechalcogenides CH2=CHPXH2 (X = O, S, Se). According to the quantum-chemical calculations on the level of the second order perturbation theory MP2/6-311G** the prevailing conformations, their molar ratios, and relative energies were established for each compound. The analysis of the angular distribution of the probability density for the population of the rotational conformations calculated proceeding from the potential curves of the internal rotation made it possible to establish that each compound from this series existed as a mixture of two conformers, planar s-cis and twice degenerate orthogonal. The conformers transform into each other through the corresponding transition states whose nature was established as a result of the harmonic vibration analysis carried out in every case.

13C-13C spin-spin coupling constants in structural studies: XLIV. Carbonyl-containing oximes

13C-13C spin-spin coupling constants in carbonyl-containing oximes were calculated in terms of the second-order polarization propagator approximation (SOPPA) with account taken of the results of theoretical conformational analysis. Stable conformations of all carbonyl-containing oximes were found to have s-trans orientation of the carbonyl group in the E and Z isomers. The corresponding 13C-13C coupling constants showed a characteristic dependence upon internal rotation of the carbonyl-containing substituent, which may be used to determine predominant rotational conformations of these compounds. A relation between orientation of the C=O bond and 13C-13C coupling constants for the adjacent bonds in oximes was revealed; it may be attributed to hyperconjugation between the corresponding carbon-carbon bond and antibonding orbital of the C=O bond.

Theoretical conformational analysis of divinyl selenide

Theoretical conformational analysis of divinyl selenide was performed in terms of the Moller-Plesset second-order perturbation theory (MP2/6-311G**). Angular distribution of the probability density of populations of its rotational conformers was determined by analysis of the rotational potential energy surface. Divinyl sulfide was found to exist as an equilibrium mixture of three conformers having essentially nonplanar structure; the major conformer is syn-s-cis-s-trans, and the two others are syn- and anti-s-trans-s-trans with higher energy.

Influence of the Introduction of Short Alkyl Chains in Poly(2-(2-Thienyl)-1H-pyrrole) on Its Electrochromic Behavior

We report the significant effect of the introduction of short alkyl chains on the electrochromic behavior of poly(2-(2-thienyl)-1H-pyrrole), poly(1). Hence, poly(3-ethyl-2-(2-thienyl)-1H-pyrrole), poly(2), and poly(3-n-propyl-2-(2-thienyl)-1H-pyrrole), poly(3), presented multicolor electrochromism (both cathodic and anodic) exhibiting several colors: blue-grayish (+0.8 V), light blue (+0.2 V), light brown (0 V), brown (−0.1 V), dark orange (−0.2 V) and light orange (−0.8 V). Both poly(2) and poly(3) films showed a maximum optical contrast (ΔTmax) of ∼30% at a film thickness <100 nm. For both polymers, the optical responses for the oxidation and reduction process were in the range of a few seconds with a coloration efficiency during the bleaching process of 107−108 cm2/C. The new multichromic polymers were thermally stable up to 200 °C and showed reduced weight loss in the temperature range from 400 to 800 °C. The doping level for poly(2) and poly(3) was in the range of 26−31%. AFM images illustrated that poly(2) presented a much rougher surface than poly(3). The morphology corresponding to the oxidized state for both polymers was sharp, showing a significant smoothening of the surface upon reduction. Geometry optimizations and theoretical conformational analysis performed at the B3LYP/6-311G* level pointed to an increased population of s-cis conformers in 2 and 3 that presumably will be also retained in poly(2) and poly(3).

Theoretical conformational analysis of substituted nitroethenes in solution

Theoretical conformational analysis of 1-nitro- and 1-bromo-1-nitro-2-(trichloromethyl)ethenes dissolved in methylene chloride and benzene was carried out by the B3LYP/6-31G* method. The calculated structures of these compounds were found to nicely fit experiment: Both in the gas phase and in solution, 1-nitro-(2-trichloromethyl)ethene is an E isomer, while its bromine-containing analog is a Z isomer.

Triosmium cluster with the bridging aminooxime derivative of pinane: Synthesis, crystal structure and conformational analysis

The reaction of 1R,2R,5R-2-dimethylamino-2,6,6-trimethylbicyclo[3.1.1]heptane-3-one oxime (pinaneoxime) with Os3(CO)10(NCMe)2 was used to synthesize the (μ-H)Os3(μ-κ1-O-N=C12H21N)(CO)10 cluster with coordination of the ligand through the oxime O atom and invariable terpenoid structure. The structure of the synthesized cluster was determined by X-ray diffraction analysis. The theoretical conformational analysis of the above cluster in a solution and in crystal state was performed by a combined MM3/MERA method. The rotation of a ligand about the O(1)-N(2) bond was found impossible due to a high energy barrier (E > 550 kJ/mol).

Gas-phase molecular structures of substituted 1,3-bisketenes: A challenge for theory and experiment

Molecular structures of dimethylbis(trimethylsilylketyl)silane (Me 2Si[C(SiMe 3) C O] 2), dimethylbis(trimethylgermylketyl)silane (Me 2Si[C(GeMe 3) C O] 2), and dimethylbis(trimethylstannylketyl)germane (Me 2Ge[C(SnMe 3) C O] 2) have been studied in the gas phase by electron diffraction accompanied by high level ab initio and DFT calculations. Extensive theoretical conformational analyses of the molecules in the vapour predicted a possibility of existence of two types of conformers with small energy differences. The first type had gauche– gauche arrangements of the ketenyl groups in the central C( C O)XC( C O) fragments directed away from each other. The second type had nearly syn– gauche arrangements of the ketenyl groups. In addition, the energy differences were found to depend on the level of computations used. The experimental analysis, in turn, was unable to distinguish between different conformers due to the large number of similar overlapping distances. The experimental data were fitted by an averaged single-conformer model, which nevertheless allowed reliable determination of bonds and bonded angles in the molecules. Main experimental ( r h1) structural parameters for Me 2Si[C(SiMe 3) C O] 2, Me 2Si[C(GeMe 3) C O] 2, and Me 2Ge[C(SnMe 3) C O] 2, i.e. Me 2X[C(YMe 3) C O] 2 (X,Y = Si, Ge, Sn), are (X–C) mean 187.7(1) pm, 194.6(2) pm, 216.1(3) pm; (Y–C) mean, 187.7(1) pm, 188.8(8) pm, 194.6(4) pm; (C C) mean, 135.3(5) pm, 131.6(5) pm, 131.5(13) pm; (C O) mean, 117.0(7) pm, 117.4(7) pm, 119.0(11) pm; (C–H) mean, 110.6(7) pm, 110.0(4) pm, 109.1(13) pm; (X(Y)–C C) mean, 114.4(2)°, 115.6(1)°, 115.6(2)°; (C–X(Y)–C Me) mean, 108.3(3)°, 108.4(3)°, 108.9(13)°; C(2)–C(1)–Y(4)–C(10), −19(6)°, 5(4)°, −9(10)°; C(7)–C(6)–Y(9)–C(38),−22(7)°, −32(3)°, −9(10)°; C(2)–C(1)–X(5)–C(6), 128(4)°, 142(1)°, 108(9)°; C(7)–C(6)–X(5)–C(1), 92(6)°, 115(2)°, 108(9)°, respectively.

Computation techniques in the conformational analysis of carbohydrates

A growing number of modern studies of carbohydrates is devoted to spatial mechanisms of their participation in the cell recognition processes and directed design of inhibitors of these processes. Any progress in this field is impossible without the development of theoretical conformational analysis of carbohydrates. In this review, we generalize literature data on the potentialities of using of different molecular-mechanic force fields, the methods of quantum mechanics, and molecular dynamics to study the conformation of glycoside bond. A possibility of analyzing the reactivity of carbohydrates with the computation techniques is also discussed in brief.

Calculation of conformations and vibrational spectra of a monomeric fragment of the 2,6-carboxymethyl cellulose molecule

A theoretical conformational analysis has been carried out for the side substituents of a fragment of the molecule for 2,6-carboxymethyl cellulose (a water-soluble cellulose ether), and the frequencies and the potential energy distribution of the normal vibrations have been calculated for the most stable conformers of the ether groups of this fragment in the approximation of the molecular mechanics method. It has been shown that the most stable conformers are those that have the conformations gg, t, g−, g−, g−-for the groups of atoms on the bonds C5-C6, C6-O6, C13-O6, C10-C13, C10-O9 and the conformations g+g−, g+, g−, g−; g+g−, g−, g−, g−; g+g−, g−, g+, t for the groups of atoms on the bonds C2-O2, C11-O2, C7-C11, C7-O8. Comparative analysis of the calculated frequencies and the potential energy distribution of the normal vibrations for 13 of the most stable conformers showed, as in the case of the 2,6-hydroxyethyl cellulose molecule, that the frequencies and modes of the normal vibrations are highly sensitive to conformational transitions in the analyzed spectral region (800–1500 cm−1). The characteristic patterns for the change in the frequencies and modes of the normal vibrations have been established in connection with conformational transitions within both side substituents. The observed conformational lability of the bulky substituents in the cellulose ether molecules and its manifestations in the vibrational spectrum provide a basis for hypothesizing that one of the major mechanisms for the process of their thermal gelation in aqueous solutions is conformational transitions within these substituents.