Molecular orbital prediction conformation

Agonists - The existence of two receptor populations for histamine raises the interesting question of whether the chemical mechanism of histamine interaction differs between the two receptor types. Some indications of the chemical properties which may differentiate receptor action come from studies of histamine chemistry and from structure-activity considerations of congeners. Histamine in aqueous solution is a mixture of equilibrating species, viz. ionic forms, tautomers and conformers nmr studies confirm earlier pK work indicating a N -H N -H (structures 1 and 2) tautomer ratio of approximately 4 1 for histamine monocation, and a comparable ratio for histamine base. The latter result contrasts with crystal structure data and molecular orbital predictions, and may indicate an influence of solvent on tautomer stability. Recent studies of properties pertinent to consideration of ligand-receptor interactions are conformation (MO calculations and infra-red comparison of solid state and chloroform solutions of histamine base ), electronic charge distribution, metal complexation, and phospholipid inter-... 

The geometries and relative energies of the different conformations of model chalcogen diimides E(NR)2 (E = S, Se R = H, Me, Bu and SiMe3) have been investigated by using ab initio and DET molecular orbital methods.The cis,trans conformation is predicted to be most stable with the exception of the parent molecules E(NH)2 and the unsymmetrical systems RNSNH, for which the cis,cis conformation is slightly more stable than the cis, trans isomer. 

Molecular orbital based molecular mechanical (MOMM) calculations have been carried out on 3H-2-benzazepinyl phosphonates.43 Similar calculations on 5//-dibenz[Z>,/]azepine lead to the prediction that there are two stable boat conformations for the seven-membered ring both of which are more stable than the planar form by 22.6 and 10.9 kJ moP, respectively the more stable conformer being the one in which the proton on nitrogen is exo lo the azepine... 

Acetylenes XCCY with n conjugated substituents, X and Y, on both carbon atoms have planar or perpendicular conformations. The substituents can be electron-donating or -accepting. The planar conformers are linear conjugate D-TI-D, D-IT-A, or A-IT-A systems whereas the perpendicular conformers are composed of ri-D and IT-A not in conjugation with each other. The orbital phase is continuous only in the planar conformations of D-TI-A (Scheme 23, cf. Scheme 4). The acetylenes with X=D (OR, NR ) and Y=A (RCO, ROCO) prefer planar conformations. When both substituents are electron-donating or accepting, the phase is discontinuous. The acetylenes then prefer perpendicular conformations. The predicted conformational preference was confirmed by ab initio molecular orbital calculations [32]. Diacetylenic molecules show similar conformational preference, which is, however, reduced as expected [32]. 

The only selenium diimide to be structurally characterized in the solid state, Se(NAd)2 (Ad=adamantyl),129 adopts the cis,trans conformation. By using ab initio and DFT molecular orbital methods, the cis,Irons conformation is predicted to be most stable for E(NR)2 (E=S, Se R=H, Me, lBu and SiMe3) with the exception of the parent molecules E(NH)2 147 and the unsymmetrical... 

A satisfactory theoretical model for ethylene oxide should take into account as many as possible of the physical properties discussed above, but should be able to predict or explain its chemical properties as well. Three such ogodels have been proposed which are based on molecular-orbital theory s 1-3W.1 ° and two more which conform rather to tho valence-bond representation of chemical structure.1M, W 7 The relative merits of all these models have been discussed in recent reviews.8 7 1301... 

Intramolecular energy calculations have been made on polygermane chains, so additional information on their conformational preferences is available 43 More specifically, molecular orbital calculations have been carried out as a function of rotations about the backbone bonds. For poly(dimethylgermane), the results predict a broad energy minimum located at the trans conformation, with two symmetrical, steeper and somewhat shallower minima near the usual gauche locations. The results are very similar to those for poly(dimethylsilane), except that the barriers are considerably lower.43 This is apparently due to the fact that Ge-Ge bonds are approximately 0.30 A longer than Si-Si bonds.44 6 Unfortunately, no relevant experimental data might be used to test the validity of the calculations are available at the present time. 

Molecular orbital calculations of varying sophistication have been used to try to predict the relative stabilities of the W, S, and U conformers. The earliest using the EHMO method predicted that the U conformer is the most stable (70), but MNDO (74) suggests that the W form is of lowest energy for the parent C5H7 anion. Most of these calculations relate to the gaseous ion, but similar conclusions were reached by inclusion of lithium or BeH (71-73). The merits and demerits of the calculations are discussed by Dewar et al. (74). 

Semiempirical molecular orbital computations have been used in numerous studies to establish various properties of heteroaromatics, such as conformations and rotational barriers. The value of such calculations is more difficult to estimate sometimes good agreement with experiment is obtained, sometimes not, making their predictional power questionable. The benefits of semiempirical MO computations are, of course, that large systems may be studied at much lower expense in terms of computer time. Thus, MINDO/3 calculations, which also take solvent effects into account, have been used to rationalize the syn-anti preference in the 2-formyl derivatives of furan, pyrrole, and thiophene (81JHC1055). 

In this connection, a very recent paper by Allinger (8) should be mentioned. A force field has been developed to permit molecular mechanics calculations on various molecular structures of elemental sulfur. The conformational characteristics of sulfur rings containing five to 12, 14, 16, 18, or 20 sulfur atoms have been examined. Comparison with experimental data is made in all cases where such data exist, and predictions are made for other cases. Ab initio molecular orbital calculations using an STO-3G basis set were carried out for cyclohexasulfur and are consistent with the molecular mechanics calculations in indicating that the chair and the twist forms are two stable conformations, with the chair about 15 kcal/mol more stable while the boat (C2t,) is a twist rotational transition state. Calculation of possible conformations of the pro-... 

Another approach which has become available in the past decade is the use of all-valence electron, semiempirical molecular orbital theory. This approximation of quantum mechanics makes it possible to calculate for fairly large molecules, a total energy behaving in an approximately parallel fashion to the true molecular energy. The consideration of all valence electrons makes this calculated total energy sensitive to the conformation of the molecule. Thus, energy minimization as a function of bond angle variation is possible, and the prediction of a preferred conformation is a consequence. 

Molecular orbital calculations led to the prediction that two distinctly different conformations of equal preference prevailed for histamine (Figure 10) (25). The conformation of Figure 10 (bottom) was predicted to exist without any hydrogen bonding between an onium hydrogen and the ring nitrogen atom. Recent NMR analysis of an aqueous solution of histamine revealed that the two conformers predicted from EHT—MO do in fact... 

Whereas empirical force-field calculations predict a ring A boat conformation for lanost-8-en-3-one, combined empirical force-field-extended Hiickel molecular orbital calculations favour a ring A chair conformation. Europium-shift n.m.r. results indicate that the molecule adopts the latter conformation. Studies on the peracetic acid-boron trifluoride etherate Baeyer-Villiger oxidation of 4,4-dimethyl-3-keto-triterpenoids to 5-lactones (18) and their subsequent ring contraction to y-lactones have been reported. Dehydrogenation of lanost-8-en-3j8-ol with 2,3-dichloro-5,6-dicyanobenzoquinone afforded, in addition to the corresponding 7,9(1 l)-diene, the aromatic seco-lanostane derivatives (19)... 

Molecular orbital theory has been applied to the problem of cyclohexane conformations by Dewar and SchoUer.32) Preliminary results using the MINDO/2 method predict a barrier considerably lower than found experimentally. 

Molecular orbital calculations based on the principles of quantum mechanics may be used to detennine energy minima of rotating bonds and to predict preferred conformations for the molecule. By means of molecular mechanics, theoretical contbrmational analysis has found that ACh has an energy minimum for the tz torsion angle at about 84° and that the preferred confimnation of ACh corresponds clo.sely in ttqueous solution to that found in the crystal stale. 

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