Molecular mechanics calculations, structural effects

The functionalization of zinc porphyrin complexes has been studied with respect to the variation in properties. The structure and photophysics of octafluorotetraphenylporphyrin zinc complexes were studied.762 Octabromoporphyrin zinc complexes have been synthesized and the effects on the 11 NMR and redox potential of 2,3,7,8,12,13,17,18-octabromo-5,10,15,20-tetraarylporphyrin were observed.763 The chiral nonplanar porphyrin zinc 3,7,8,12,13,17,18-heptabromo-2-(2-methoxyphenyl)-5,10,15,20-tetraphenylporphyrin was synthesized and characterized.764 X-ray structures for cation radical zinc 5,10,15,20-tetra(2,6-dichlorophenyl)porphyrin and the iodinated product that results from reaction with iodine and silver(I) have been reported.765 Molecular mechanics calculations, X-ray structures, and resonance Raman spectroscopy compared the distortion due to zinc and other metal incorporation into meso dialkyl-substituted porphyrins. Zinc disfavors ruffling over doming with the total amount of nonplanar distortion reduced relative to smaller metals.766 Resonance Raman spectroscopy has also been used to study the lowest-energy triplet state of zinc tetraphenylporphyrin.767... 

In this part, two series of 44 copolymers with coiled main-chain structures and 45 copolymers with stiff main-chain conformations were described. It was concluded that both optically inactive 42 and 43 adopt helical conformations with an equal proportion of P and M screw senses by means of UV and CD spectra as well as molecular mechanics calculations. A marked positive cooperative induction effect of the preferential screw sense in 44 and 45 copolymers was found. However, there is a marked difference in the helical cooperativity between 44 and 45, probably because of the differences in their global and local conformations. This difference can be related to the persistence of the helical conformation against defects allowing change of... 

Another approach to evaluating homoaromaticity is to compute various reaction properties such as heats of reaction. A typical example of this approach is a recent paper by Storer and Houk (1992) using molecular mechanics calculations (MM2) of the heats of hydrogenation of triquinacene [118]. In this study they conclude that the anomalous heat of hydrogenation can be explained without invoking homoaromaticity. The use of this type of computational data suffers the same problems as experimentally measured values there is an ambiguity with regard to separation of structural and electronic effects and how to choose appropriate reference systems. 

From among the different classes of compounds considered in this work, most of the computational work was done on amines, while less examples are found for nitro compounds and very few for nitroso ones. The different studies may be classified into several major areas (1) conformational analysis and structural investigation (2) spectroscopic experiments and study of chemical effects (3) investigation of chemical reactions mechanism (4) heats of formation and density calculations, especially of high energetic materials. In the following sections we will concentrate on molecular mechanics based research studies, or on such where molecular mechanics calculations played a... 

There are two apparent exceptions to the rule of Hooker et al. 1,170 These are c(-Ala-Ala-) and c[-(Me)Ala-(Me)Ala-]. The X-ray structure of c(-Ala-Ala-) 171 172 gives a positive p, but the NV couplet is observed to be negative. However, molecular mechanics calculations 173174 predict a negative p for c(-Ala-Ala-) and its A-methyl analogue, in agreement with the CD assignment, so crystal packing effects are responsible for the apparent exception. 

An inverse y-turn mimetic, containing a 3-morpholinone ring 23 (Scheme 14) as the key structural feature was prepared enantiospecifically.[43] Molecular mechanics calculations revealed that the torsional angles of the second residue of the mimetic were effectively constrained in an inverse y-turn-like conformation. 

Usually, force field parameters are developed on the basis of solid-state data, e.g., crystal structural coordinates. It is therefore not appropriate to refer to these molecular mechanics calculations as gas-phase calculations , even if the environment is not explicitly included in the structure optimization procedure. Environmental effects such as ion-pairing and hydrogen bonds to counter ions, co-crystallized solvent molecules, and neighboring molecules are present in crystal lattices. Therefore, an averaged influence of these is implicitly included in the force field and at least partially mimics a nonspecific environment, similar to that present in solution. 

The estimate of relative stabilities via the comparison of total strain energies is in general limited to a series of conformers and isomers (see for instance Chapter 7 and the relevant chapters in Parts I and III). The determination by molecular mechanics calculations of relative stabilities of a series of complexes with metal ions having differing geometric preferences (electronic effects) and preferences in terms of donor atoms is therefore a questionable approach. A comparative study is only useful if the structural preferences of the different metal ions are similar and/or if the electronic effects may be separated from steric effects. 

Because of the approximations involved in this analysis, the thermodynamic results have to be considered with caution. This is not only due to a rather crude analysis of the electrostatic effects but also, and this is a general problem, to the neglect of solvation in the molecular mechanics refinement. However, the structures presented in Fig. 9.6 are valuable because they are based not only on the structure optimization by molecular mechanics but also on spectroscopic data. This example is therefore instructive for two reasons first, it demonstrates that, depending on the study, the often-neglected electrostatic effects may be of considerable importance. Second, not only may experimental observables help to refine solution structures, they can prevent a wrong conclusion. As in this example, the combination of experimental data with molecular mechanics calculations is often the only way to get reliable structural information. 

Structure optimization of main group molecules with generic force fields has the same advantages and problems as molecular mechanics calculations of organic and organometallic compounds with similar approaches on one hand there is no need to fit a specialist force field, on the other hand is the expectation of lower accuracy1279,2801. The structural results are especially poor for molecules where electronic effects are important, e.g., those with hypervalent or dative bonds. 

Ken pioneered the modeling of transition states with force field methods. Before modem tools existed for locating transition structures in all but the simplest reactions, his group used ab initio calculations to find the geometries of transition states and to determine force constants for distortions away from these preferred geometries. These force constants could then be used in standard molecular mechanics calculations, in order to predict how steric effects would affect the geometries and energies of the transition structures when substituent were present. 

Because of the ease with which molecular mechanics calculations may be obtained, there was early recognition that inclusion of solvation effects, particularly for biological molecules associated with water, was essential to describe experimentally observed structures and phenomena [32]. The solvent, usually an aqueous phase, has a fundamental influence on the structure, thermodynamics, and dynamics of proteins at both a global and local level [3/]. Inclusion of solvent effects in a simulation of bovine pancreatic trypsin inhibitor produced a time-averaged structure much more like that observed in high-resolution X-ray studies with smaller atomic amplitudes of vibration and a fewer number of incorrect hydrogen bonds [33], High-resolution proton NMR studies of protein hydration in aqueous... 

One reason that salts of general structure 7 were chosen for investigation is that molecular mechanics calculations showed the benzocyclohexadienone framework to be planar. This planarity translates into an equal opportunity of forming either enantiomer of photoproduct 8, or to put it another way, the photochemistry of these salts is conformationally unbiased with respect to enantioselec-tivity. As a result, any ee in the crystalline state would have to be due to an essentially pure topochemical effect. Only one of the salts investigated (7b) gave a respectable ee in the solid state, and unfortunately, it has not been possible to obtain an X-ray crystal structure of this material, thus precluding an analysis of the specific topochemical factors responsible for asymmetric induction in this case. 

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