Conformational by molecular mechanics

Make molecular models of the two chair conformations of cis 1 tert butyl 4 phenyl cyclohexane What is the strain energy calculated for each conformation by molecular mechanics Which has a greater preference for the equatorial onentation phenyl or tert butyD... 

Empirical force-field (EFF) calculations failed to predict the A-ring chair conformation of lanost-8-en-3-one, which was indicated by n.m.r. studies. Combined EFF-extended Hiickel MO calculations were successful, however, giving a preference of 1.14 kcal mol over the boat form, although quantitative accuracy is not claimed for the present method of calculation. A treatment of alcohol conformations by molecular mechanics may have applications in predicting the preferred conformations of hydroxy-steroids. 

An example illustrates the point Suppose a blind person stands before an undulated model surface. She must find the deepest basins on this surface by throwing balls on it. She detects height acoustically. Even if this person has a very sophisticated technique of throwing balls on the surface, different runs will lead to different results. She does not deduce the deepest basin on the surface.11 In the same way, the actual process of deriving stable conformations by molecular mechanics is not entirely deductive.12... 

Fig. 2.29 Calculated PI conformations by molecular mechanics method. Reproduction by permission from [33].

Figure 4.18 The structure of Tamiflu (oseltamivir phosphate), an antiviral agent active against type A influenza, and a molecular model of its minimum-energy conformation, as calculated by molecular mechanics.

Using molecular mechanics calculations to assess the three-dimensional shape of a molecule, various surface properties such as polarity and size can be calculated. The dynamic molecular surface properties can be determined from the (low energy) conformation(s) of the drug molecule obtained by molecular mechanics calculations of conformational preferences. The potential advantage of this method is that the calculated surface character-sitics determine numerous physicochemical properties of the molecules including lipophilicity, the energy of hydration and the hydrogen bond formation capacity [187-... 

The conformation of the mixed p agonist/5 antagonist H-Tyr-c[-D-Orn-2-Nal-D-Pro-Gly-] in comparison to that of H-Tyr-c[-D-Orn-Phe-D-Pro-Gly-] was studied in DMSO-d6 by NMR spectroscopy and by molecular mechanics calculations [62,64]. Neither peptide showed nuclear Overhauser effects between C H protons or chemical exchange cross peaks in spectra obtained by total correlation and rotating frame Overhauser enhance-... 

Schei, S. H. 1984a. 3-Chloro-l-Butene Gas-Phase Molecular Structure and Conformations as Determined by Electron Diffraction and by Molecular Mechanics and Ab Initio Calculations. J. Mol. Struct. 118, 319-332. 

Fig. 33 (a) AMI-optimised transition state for reaction of IV-formyloxy-lV-methoxyform-amide with G-N7 (b) conformation of 31b in the major groove of DNA constrained to transition state in (a) with side chains minimised by molecular mechanics. 

Semiempirical and molecular mechanics calculations have been widely used. Thus, conformation of indolo benzazepine 423 (Figure 8) with its conjugated benzo and indole rings has been studied by molecular mechanics (MMX force field). Its planarity was estimated from a calculation of dihedral angle Ti 2 3 4 the value of ca. 22° is due to strain as contributed by azepine ring. This characteristic was further compared to that of the open-chain and six-membered... 

For CH3SC50 four local conformational minima are obtained by molecular mechanics calculations using the MMX force field (Figure 6.4) [7]. Thereby, as shown in Figure 6.4, the asymmetric conformation for this radical is preferred. 

Figure 6.4 Structures of the preferred local conformational minima of the radical CHjSC q" obtained by molecular mechanics calculations [7. ...

In the case of flexible molecules all chiral conformers contribute to the observed CD spectrum. This usually leads to substantial reduction of the magnitude of the exciton Cotton effect. Nevertheless, if the conformation of the main contributor is established independently (e.g.. by molecular mechanics or NMR spectroscopy), its absolute configuration can be deduced from the exciton Cotton effect. Thus, for 3-(l-naphthalenyl)phthalide 5, the preferred conformation is 5 a. The negative couplet is in accordance with the left-handed screw between the phthalide 1 Ld and the naphthalene lBb transition dipole moment vectors, when the absolute configuration is R121. 

There are two principal methods of performing computational conformational analyses Molecular mechanics(18-19) and quantum mechanics.(20) Molecular mechanics consideres a molecule as a set of balls (the atoms), coated with sticking paste, connected by a set of springs (the bonds) according to a prescribed set of valence angles. Quantum mechanics views the molecule as a set of nuclei in space with electrons moving about the nuclei. 

A second major area of interest in the design of bioactive molecules is that of the process of molecular recognition which is vital to the formation of the bas-rep complex. The functional groups required for recognition and activity, in their appropriate arrangement in space, or conformation, constitute the pharmacophore of a bas. The study of the possible conformations of a bas may be carried out by molecular mechanics or quantum chemical calculations. Another important factor is the nature and geometry of the receptor site. 

---