Evidence for the importance of conformational equilibria in Rh-diphosphine complexes for the enantioselection in Rh-catalyzed asymmetric hydrogenation

The conformations of the chelate cycles in the X-ray structures of norbornadiene- and cyclooctadiene-rhodium complexes of (R,R)-1,2-bis[(o-methylphenyl)phenylphosphino]ethane are dramatically different. Nevertheless, they demonstrate the same sense of enantioselection in asymmetric hydrogenation of dehydroamino acids.     

Compensation effect in the thermodynamics of conformational equilibria

The solvent dependence of thermodynamic parameters of conformational equilibria in trans-1,2-dichlorocyclohexane and trans-1,2-bromochlorocyclohexane was investigated by infrared absorption spectra. The results obtained show the existence of a compensation effect in the thermodynamics of conformational equilibria: the enthalpy (ΔH₀) and entropy (ΔS₀) differences change in the same direction when going from one solvent to another. A semi-quantitative estimation of the effect is given on the basis of the equations of statistical thermodynamics. It is shown that the temperature dependence of the ΔS₀ value must be taken into account when determining the enthalpy difference of the conformers. This yields the equality of the true and observed ΔH₀ values.     

Dielectric studies of conformational equilibria in acetylpyridines

Results of both linear and non-linear dielectric studies of the tautomeric equilibria in benzene solutions of 2- and 4-acetylpyridines are presented. The suggestion that 2-acetylpyridine occurs only in its trans conformation has been confirmed. The analysis for 4-acetylpyridine has shown the correctness and specific utility of the dielectric methods (particularly the non-linear) to studies of conformational equilibria.     

Electronic structure and conformational equilibria of phenyl-propylcarbocations

Modified CNDO calculations were performed on different conformations of various phenyl propyl cations and related compounds. Molecular energies and electronic structures are presented and discussed. A substituted secondary benzyl cation, the 1-phenyl-1-propyl carbocation (12) is found to be the most stable isomer. The open chain 1-phenyl-2-propyl carbocation (11b) has a lower energy than the propylene benzenium cation (11d). In contrary, previous calculations of 2-phenyl-1-ethyl cation lead to the result that in this case the ethylene benzenium cation is the most stable structure. Rotational barriers for different substituted 1-propyl and 2-propyl cations were calculated. The results are explained by hyperconjugative stabilization.     

Fluctuation theory of molecular association and conformational equilibria

General expressions relating the effects of pressure, temperature, and composition on solute association and conformational equilibria using the fluctuation theory of solutions are provided. The expressions are exact and can be used to interpret experimental or computer simulation data for any multicomponent mixture involving molecules of any size and character at any composition. The relationships involve particle-particle, particle-energy, and energy-energy correlations within local regions in the vicinity of each species involved in the equilibrium. In particular, it is demonstrated that the results can be used to study peptide and protein association or aggregation, protein denaturation, and protein-ligand binding. Exactly how the relevant fluctuating properties may be obtained from experimental or computer simulation data are also outlined. It is shown that the enthalpy, heat capacity, and compressibility differences associated with the equilibrium process can, in principle, be obtained from a single simulation. Fluctuation based expressions for partial molar heat capacities, thermal expansions, and isothermal compressibilities are also provided.     

Effect of lanthanide shift reagents on conformational equilibria

The conformational equilibrium constants for a series of 1-alkyl substituted cyclohexanols have been determined using a lanthanide shift reagent, and the results compared with other methods. In comparison to other technique greater preference is shown by the hydroxyl group for the equatorial position. This is rationalized by the effect on the equilibrium of the bulky shift reagent.     

Toward functional carboxylate-bridged diiron protein mimics: achieving structural stability and conformational flexibility using a macrocylic ligand framework

A dinucleating macrocycle, H(2)PIM, containing phenoxylimine metal-binding units has been prepared. Reaction of H(2)PIM with [Fe(2)(Mes)(4)] (Mes = 2,4,6-trimethylphenyl) and sterically hindered carboxylic acids, Ph(3)CCO(2)H or Ar(Tol)CO(2)H (2,6-bis(p-tolyl)benzoic acid), afforded complexes [Fe(2)(PIM)(Ph(3)CCO(2))(2)] (1) and [Fe(2)(PIM)(Ar(Tol)CO(2))(2)] (2), respectively. X-ray diffraction studies revealed that these diiron(II) complexes closely mimic the active site structures of the hydroxylase components of bacterial multicomponent monooxygenases (BMMs), particularly the syn disposition of the nitrogen donor atoms and the bridging μ-η(1)η(2) and μ-η(1)η(1) modes of the carboxylate ligands at the diiron(II) centers. Cyclic voltammograms of 1 and 2 displayed quasi-reversible redox couples at +16 and +108 mV vs ferrocene/ferrocenium, respectively. Treatment of 2 with silver perchlorate afforded a silver(I)/iron(III) heterodimetallic complex, [Fe(2)(μ-OH)(2)(ClO(4))(2)(PIM)(Ar(Tol)CO(2))Ag] (3), which was structurally and spectroscopically characterized. Complexes 1 and 2 both react rapidly with dioxygen. Oxygenation of 1 afforded a (μ-hydroxo)diiron(III) complex [Fe(2)(μ-OH)(PIM)(Ph(3)CCO(2))(3)] (4), a hexa(μ-hydroxo)tetrairon(III) complex [Fe(4)(μ-OH)(6)(PIM)(2)(Ph(3)CCO(2))(2)] (5), and an unidentified iron(III) species. Oxygenation of 2 exclusively formed di(carboxylato)diiron(III) compounds, a testimony to the role of the macrocylic ligand in preserving the dinuclear iron center under oxidizing conditions. X-ray crystallographic and (57)Fe M?ssbauer spectroscopic investigations indicated that 2 reacts with dioxygen to give a mixture of (μ-oxo)diiron(III) [Fe(2)(μ-O)(PIM)(Ar(Tol)CO(2))(2)] (6) and di(μ-hydroxo)diiron(III) [Fe(2)(μ-OH)(2)(PIM)(Ar(Tol)CO(2))(2)] (7) units in the same crystal lattice. Compounds 6 and 7 spontaneously convert to a tetrairon(III) complex, [Fe(4)(μ-OH)(6)(PIM)(2)(Ar(Tol)CO(2))(2)] (8), when treated with excess H(2)O.     

Raman study on conformational equilibria of fluoroacetone in aqueous solutions

The effects of water and heavy water on conformational equilibria of fluoroacetone have been investigated via Raman spectroscopy. Additional Raman bands have been observed in the C-F stretching and the C-C-C symmetric stretching regions for the aqueous solutions. Based on enthalpy and volume differences between the conformers, these bands are assigned to the syn conformer which has hydrogen bonds between the fluorine atom and water molecules (syn' conformer). The number of H2O molecules binding to the syn' conformer is estimated to be 2.4 from the concentration dependence of the spectrum. The enthalpy and the volume differences between the cis and syn conformers in the aqueous solutions show anomalous values in comparison with those in organic solvents. We discuss these thermodynamic behaviors from the viewpoint of the hydration structures of fluoroacetone.     

Metal ligation regulates conformational equilibria and binding properties of cavitands

A self-folding cavitand binds quinuclidinium cation in its vase conformation and lanthanum ions in its kite conformation. Metal coordination provides a novel switching mechanism for the uptake and release of guests.     

Analytical applications of mixed ligand extraction equilibria Nickel-ditbizone-phenanthroline complex

The mixed ligand nickel-dithizone-phenanthroline complex provides a sensitive method for determination of nickel and also permits evaluation of the extraction constant for nickel dithizonate. The value log K(ex) = -0.7 was obtained, in agreement with a value of -0.2 obtained by others, and in contrast to an earlier value of -2.9. The addition of phenanthroline substantially increases the rate of extraction.     

Control of the conformational equilibria in aza-cis-decalins: structural modification,solvation, and metal chelation

A series of amino alcohol- and diamino-cis-decalins were synthesized and their conformational properties investigated. The equilibrium distributions of the conformational isomers were measured via NMR spectroscopy. The equilibrium ratios depend on the position of the substituents on the decalin ring system and the solvent. The 7-substituted 1-aza-cis-decalins are more likely to adopt the N-in form than the 5-substituted analogues. The N-in form is generally favored in nonpolar solvents, while the N-out form is favored in polar solvents. Complexation with LiClO4 and Et2Zn alters the equilibrium to favor the N-in decalin conformer. Both conformers coordinate lithium ions such that "on/off" conformational switching is not observed for these decalins. Comparison of the results with complexation studies of (-)-sparteine allows the criteria for an ideal "on/off" conformational switch to be defined.     

'Objective' determination of coupling constants and conformational equilibria by solvent variation: a comment

Following the preceding paper, the 'objective' method of Abraham et al. for determining the conformational equilibrium between molecules rapidly interconverting between a number of different conformers has been re-evaluated. The method relies on the acquisition of a sufficient data set of nuclear couplings in different solvents to obtain an over-determined system with more equations than unknowns. The example considered by Deutsch and Roberts, of 1,2-dichloro-1-fluoroethane, is re-evaluated here. A simple but mathematically rigorous computer scanning process is used to analyse the data set instead of the iterative but not mathematically rigorous process used previously and the results compared with those of Deutsch and Roberts. It is shown that both treatments give similar solutions. However, it is emphasized that in these multi-dimensional analyses the probable errors in the derived parameters (in this case the conformer couplings) may be much larger than the r.m.s. (observed versus calculated) errors and this error analysis is essential for a considered appraisal of the method.     

Isotope effects—III: Hydrogen isotope effects on conformational equilibria derivatives of cyclohexane

Conformational equilibrium isotope effects (in J mol^?1) have been measured for deuteriation of one methyl or methylene group in the trans stereoisomers of 1,3-dimethylcyclohexane (?46 ±10), 2,6- (?80 ±28) and 3,5-dimethylcyclohexanone (?40 ±15), and 3-methyl- (48 ±3) and 3-hydroxymethyl 1-trifluoromethylcyclohexane (45—49 ± 3 in toluene, acetone or methanol). The observed effects are independent of solvent for the hydroxymethyl group The isotope effects for the methyl group in trans-4 are proportional to the number of deuterium atoms.     

'Objective' determination of coupling constants and conformational equilibria by solvent variation: a re-evaluation

An 'objective' method for determining conformational equilibria in substituted ethanes, proposed by Abraham et al., has been evaluated by computational methods. Abraham's method involves measuring vicinal couplings, such as (3)J(H,H) and (3)J(H,F), between methine and methylene protons with methine, methylene protons and fluorine in a range of solvents, on the assumption that the underlying coupling constants of the individual conformers are constant, but the fractions of each conformer in each solvent are different and unknown. Abraham posited that this would produce an 'over-determined' data set with more equations than unknowns would. Abraham's procedure is re-evaluated, and it is demonstrated that the type of system being considered here, where there are more equations than unknowns, is not necessarily over-determined. A computer equation solver and Monte Carlo-type procedures were employed to demonstrate that multiple numerical solutions exist for a representative 'over-determined' data set provided by Abraham. A statistical method was also developed to determine precisely which parameter sets constitute plausible solutions.     

Importance of ligand conformational energies in carbohydrate docking: Sorting the wheat from the chaff

Docking algorithms that aim to be applicable to a broad range of ligands suffer reduced accuracy because they are unable to incorporate ligand‐specific conformational energies. Here, we develop a set of Carbohydrate Intrinsic (CHI) energy functions that quantify the conformational properties of oligosaccharides, based on the values of their glycosidic torsion angles. The relative energies predicted by the CHI energy functions mirror the conformational distributions of glycosidic linkages determined from a survey of oligosaccharide‐protein complexes in the protein data bank. Addition of CHI energies to the standard docking scores in Autodock 3, 4.2, and Vina consistently improves pose ranking of oligosaccharides docked to a set of anticarbohydrate antibodies. The CHI energy functions are also independent of docking algorithm, and with minor modifications, may be incorporated into both theoretical modeling methods, and experimental NMR or X‐ray structure refinement programs. © 2013 Wiley Periodicals, Inc.