Conformational isomerism

About: Conformational isomerism is a research topic. Over the lifetime, 11563 publications have been published within this topic receiving 199312 citations.

Dynamic proton magnetic resonance studies on complex spin systems. Non‐mutual three‐spin exchange in four 1‐substituted cyclohexanes‐2,2,3,3,4,4,5,5‐d8 and mutual four‐spin exchange in cyclohexane‐1,1,2,2,3,3,4,4‐d8

Abstract: The intrinsic advantage proffered by coupled three-proton spin systems in the quantitative study of conformational equilibria and equilibrations, as elaborated and exemplified in the preceding publication, is exploited for the determination of precise thermodynamic and dynamic parameters for octadeuteriocyclohexanes containing a cyano, chloro, bromo or deuteriomethoxy substituent and hydrogen atoms on the substituted and on one contiguous carbon. Dynamic quantities for the ring reversal of cyclohexane-1,1,2,2,3,3,4,4-d8, obtained by bandshape analysis of the deuterium-decoupled proton NMR spectra broadened by mutual four-spin exchange, are also reported. The measured standard entropy differences between the axial and equatorial conformational isomers of the monosubstituted cyclohexanes show that, in addition to the rotational entropy, there must be a significant contribution from the vibrational partition functions. The experimental activation entropies for the cyclohexane chair-to-twist-boat conversion are at variance with conclusions drawn from naive symmetry considerations, but agree with the more sophisticated treatment of Pickett and Strauss; the data establish that there is virtually free pseudorotation in the transition states of the ring reversal for cyclohexane itself as well as for the monosubstituted derivatives studied in this investigation.

Characterization of amide bond conformers for a novel heterocyclic template of N-acylhydrazone derivatives.

Abstract: Herein we describe NMR experiments and structural modifications of 4-methyl-2-phenylpyrimidine-N-acylhydrazone compounds (aryl-NAH) in order to discover if duplication of some signals in their ¹H- and ¹³C-NMR spectra was related to a mixture of imine double bond stereoisomers (E/Z) or CO-NH bond conformers (syn and anti-periplanar). NMR data from NOEdiff, 2D-NOESY and ¹H-NMR spectra at different temperatures, and also the synthesis of isopropylidene hydrazone revealed the nature of duplicated signals of a 4-methyl-2-phenylpyrimidine-N-acylhydrazone derivative as a mixture of two conformers in solution. Further we investigated the stereoelectronic influence of substituents at the ortho position on the pyrimidine ring with respect to the carbonyl group, as well as the electronic effects of pyrimidine by changing it to phenyl. The conformer equilibrium was attributed to the decoplanarization of the aromatic ring and carbonyl group (generated by an ortho-alkyl group) and/or the electron withdrawing character of the pyrimidine ring. Both effects increased the rotational barrier of the C-N amide bond, as verified by the DG(≠) values calculated from dynamic NMR. As far as we know, it is the first description of aryl-NAH compounds presenting two CO-NH bond- related conformations.

Pure Samples of Individual Conformers: The Separation of Stereoisomers of Complex Molecules Using Electric Fields

Abstract: Many complex molecules have multiple structural isomers; that is, multiple local minima on their potential energy surface. About twenty-five years ago, it was observed that multiple conformers of tryptophan are present even at the low temperatures of a few Kelvin in a supersonic jet. These conformers have been studied extensively since then with sophisticated spectroscopic techniques. Individual conformers can be identified from their distinct electronic or microwave spectra. Information on the conformational structures can be obtained using microwave or multipleresonance infrared spectroscopy, for example. In similar experiments it was even possible to obtain information on the barriers separating the conformers. The preparation of spatially separated conformers would provide unique possibilities for advanced further investigations. The chemical properties of the individual species and their differences could be directly studied in reactive scattering experiments. Such pure samples would also enable a new class of experiments, such as electron and X-ray diffraction or tomographic imaging experiments of complex molecules in the gas phase. Molecular-frame photoelectron angular distributions, ultrafast time-resolved photoelectron spectroscopy, and ultrafast dynamics studies would also benefit from the availability of these pure samples. For charged species, the separation of molecules with different shapes has been demonstrated by utilizing ion mobility in drift tubes. For neutral molecules, the abundance of the conformers in molecular beams can be partly influenced by selective over-the-barrier excitation in the early stage of the expansion or by changing the carrier gas. Herein, we demonstrate that electrostatic deflection, a classic molecular beam manipulation method that dates back to the 1920s, allows the spatial separation of the conformers of a neutral molecule when it is applied to intense beams of rotationally cold molecules produced by a state-ofthe-art pulsed supersonic expansion source. The idea of exploiting electrostatic deflection to separate quantum states was already conceived by Stern in 1926 for light diatomic molecules, and these ideas were recently extended to proposals for the separation of conformers of large molecules. Polar molecules experience a force in an inhomogeneous electric field. This force is due to the spatial variation in the potential energy of the molecules, and is given by F ! = meff·r ! E. The effective dipole moment meff of a molecule in a given quantum state is the negative gradient of the potential energy with respect to the electric field strength E. This force has been used to decelerate small molecules in a supersonic jet to a standstill and subsequently trap them. Similarly, large neutral molecules have been deflected, focused, and decelerated. Passing polar molecules through a strong inhomogenous electric field will spatially disperse them according to their effective dipole moment. In particular, the conformers of a specific biomolecule all have the same mass m, but differ by the relative orientations of their functional groups. Typically, these functional groups have large local dipole moments associated with them, and the vectorial sum of these local dipole moments largely determines the overall dipole moment of the molecule. Herein, we show that the resulting different overall dipole moments of the conformers can be exploited to select individual conformers using an electrostatic deflector. The cis and trans conformers of 3-aminophenol (Figure 1) are used herein as prototypical structural isomers of complex molecules. From the precisely known rotational constants and dipole moments, the energies of the rotational states of cis3-aminophenol and trans-3-aminophenol are calculated as a function of electric field strength. Figure 1 shows the resulting Stark curves for the lowest rotational states of both species. From Figure 1, it is obvious that the effective dipole moments meff of the states of cis-3-aminophenol are considerably larger than for trans-3-aminophenol, and therefore, a strong spatial separation of the conformers is expected. The results on the separation of the cis and trans conformers of 3-aminophenol are complementary to our previous experiments on the separation of the same species using an ac (alternating current) focusing device, and we will briefly discuss the merits of the individual techniques in the Summary. The experimental setup is shown in Figure 2, and a detailed description is given elsewhere. 3-aminophenol (Sigma–Aldrich, 98%), seeded in 90 bar of helium, is released from a pulsed valve into high vacuum. The molecular beam is [*] F. Filsinger, Dr. J. K pper, Prof. Dr. G. Meijer Fritz-Haber-Institut der Max-Planck-Gesellschaft Faradayweg 4–6, 14195 Berlin (Germany) Fax: (+49)30-8413-5892 http://www.fhi-berlin.mpg.de/mp/jochen E-mail: jochen@fhi-berlin.mpg.de

Importance of entropy in the conformational equilibrium of phenylalanine: a matrix-isolation infrared spectroscopy and density functional theory study.

Abstract: The conformational behavior and infrared spectrum of l-phenylalanine were studied by matrix-isolation infrared spectroscopy and DFT [B3LYP/6-311++G(d,p)] calculations. The fourteen most stable structures were predicted to differ in energy by less than 10 kJ mol(-1), eight of them with abundances higher than 5% at the temperature of evaporation of the compound (423 K). Experimental results suggest that six conformers contribute to the spectrum of the isolated compound, whereas two conformers (IIb(3) and IIIb(3)) relax in matrix to a more stable form (IIb(2)) due to low energy barriers for conformational isomerization (conformational cooling). The two lowest-energy conformers (Ib(1), Ia) differ only in the arrangement of the amino acid group relative to the phenyl ring; they exhibit a relatively strong stabilizing intramolecular hydrogen bond of the O-H...N type and the carboxylic group in the trans configuration (O=C-O-H dihedral angle ca. 180 degrees ). Type II conformers have a weaker H-bond of the N-H...O=C type, but they bear the more favorable cis arrangement of the carboxylic group. Being considerably more flexible, type II conformers are stabilized by entropy and the relative abundances of two conformers of this type (IIb(2) and IIc(1)) are shown to significantly increase with temperature due to entropic stabilization. At 423 K, these conformers are found to be the first and third most abundant species present in the conformational equilibrium, with relative populations of ca. 15% each, whereas their populations could be expected to be only ca. 5% if entropy effects were not taken into consideration. Indeed, phenylalanine can be considered a notable example of a molecule where entropy plays an essential role in determining the relative abundance of the possible low-energy conformational states and then, the thermodynamics of the compound, even at moderate temperatures. Upon UV irradiation (lambda > 235 nm) of the matrix-isolated compound, unimolecular photodecomposition of phenylalanine is observed with production of CO(2) and phenethylamine.