Supermolecule models

Since the approach angle was not optimized in these calculations, a separate assessment of the factors governing deviation from the direction normal to the carbonyl plane was made. Energy optimization for the model supermolecule HCHO-l-H" (fixed distance 1.5 A) and overlap calculations for H" and jt (C=0) were carried out for approach angles from 90° to 115° by increments of 5°. The optimal angle was found to be 110°. The authors concluded that the deviation is due almost entirely to the interaction with the 7t (C=O) orbital, since maximal overlap is obtained for 105°. 

MI + MLg M = Fe, Co, or Ru, L = H2O or NH3, have been analyzed in terms of various orbital concepts. The matrix elements are based on ab initio wavefunctions for model supermolecule clusters of the type,... 

On one hand, there are the dielectric properties, which are especially important for polai solvents like water. Bulk properties can, on the other hand, only be modeled by using a supermolecule approach with explicitly defined solvent molecules. 

In the second group come molecular dynamics and Monte Carlo simulations, especially those where the solvent is modelled without being explicitly included. Their fourth class is the related supermolecule class, where we actually include solvent molecules in the simulation, and treat the entire array of molecules according to the rules of quantum mechanics or whatever. 

The simplest discrete approach is the solvaton method 65) which calculates above all the electrostatic interaction between the molecule and the solvent. The solvent is represented by a Active molecule built up from so-called solvatones. The most sophisticated discrete model is the supermolecule approach 661 in which the solvent molecules are included in the quantum chemical calculation as individual molecules. Here, information about the structure of the solvent cage and about the specific interactions between solvent and solute can be obtained. But this approach is connected with a great effort, because a lot of optimizations of geometry with ab initio calculations should be completed 67). A very simple supermolecule (CH3+ + 2 solvent molecules) was calculated with a semiempirical method in Ref.15). 

The continuum models represent a real alternative to the supermolecule approach. In this cases the solvation energy Esolv is assumed to be a sum of individual terms which can be calculated separately (see Eq. (6)). 

In Eq. (6) Ecav represents the energy necessary to create a cavity in the solvent continuum. Eel and Eydw depict the electrostatic and van-der-Waals interactions between solute and the solvent after the solute is brought into the cavity, respectively. The van-der-Waals interactions divide themselves into dispersion and repulsion interactions (Ed sp, Erep). Specific interactions between solute and solvent such as H-bridges and association can only be considered by additional assumptions because the solvent is characterized as a structureless and polarizable medium by macroscopic constants such as dielectric constant, surface tension and volume extension coefficient. The use of macroscopic physical constants in microscopic processes in progress is an approximation. Additional approximations are inherent to the continuum models since the choice of shape and size of the cavity is arbitrary. Entropic effects are considered neither in the continuum models nor in the supermolecule approximation. Despite these numerous approximations, continuum models were developed which produce suitabel estimations of solvation energies and effects (see Refs. 10-30 in 68)). 

In Ref.125) the calculation of an activation barrier for reaction (21) in the gas phase is considered to be an error of the MINDO/3 method and the process is assumed to be activationless. But in respect to the medium effect a barrier of 54 k J mol-1 is obtain-ed which agrees again with the results from Huron-Claverie calculations. Bertran et al. calculated the influence of the solvation on the electrophilic attack of a proton 133) or a methyl cation 134,135) on ethene using a MINDO/3 supermolecule model. Smaller reaction enthalpies also result in solution than in the gas phase in addition to the appearance (H+ + ethene) or the increase (CH 4 + ethene) of an activation barrier1361. 

Explicit calculation of the electronic coupling matrix element, Hah, is performed by modeling the transition state (Fig. 3) as a supermolecule, [M(H20)6]2+, and optimizing its geometry under the constraint of having an inversion center of symmetry The numerical value of Hab is then obtained from the energy gap between the appropriate molecular orbitals of the supermolecule. 

Supermolecule-Based Subtype Pharmacophore and QSAR Models... 

On a quantitative basis, an accurate correlation analysis was carried out and some significant linear QSAR models were obtained, based on ad hoc defined size-shape descriptors. One of the best linear correlations based on the Vin index indicated that the higher the volume shared by a generic antagonist and the supermolecule (obtained by superimposing abanoquil and WB4101, Scheme 8.1), the higher is... 

The best statistical parameters were obtained by correlating the in vivo selectivity with the Vdif descriptor defined with respect to the oqa-AR supermolecule. It is worth noting that the oqa is the adrenergic receptor subtype of functional relevance for the urethra tissue (dog model) [8]. Thus, ligands showing high potency and selectivity for the lower urinary tract are those, which better fit the volume of the supermolecule that represents the binding site of the ala-AR subtype. 

A very similar QSAR approach for the modeling and prediction of selectivity of oq-AR antagonists has recently been carried out by Eric el al. It confirms the usefulness of the supermolecules approach and of the ad hoc shape descriptors in the rationalization of cq-ARs affinity and cq-AR subtype selectivity [98]. 

Cocchi, M. and De Benedetti, P.G. (1998) Use of the supermolecule approach to derive molecular similarity descriptors for QSAR analysis. Journal of Molecular Modelling, 4, 113-131. 

Ab initio STO-3G calculationswere performed on the supermolecules formed by a nucleophile and a chiral substrate (2-chloropropanal or 2-methylbutanal). The nucleophile, simulated by H , is located at 1.5 A from the carbon atom, in a direction perpendicular to the carbonyl axis. Hence, to each reaction correspond two diastereoisomeric supermolecules resulting from attack on one face or the other of the 7T system. These molecules are thus models of the diastereoisomeric transition states. In Fig Ill and IV, their relative energies are plotted as a function of their conformations. The solid (dashed) lines correspond to the transition states of type 5... 

Metalloreceptors, and the supermolecules that they form, thus open up a vast area for the study of interactions and reactions between simultaneously co-bound organic and inorganic species [4.67,4.68]. In view of the number of metal-ion complexes known and of the various potential molecular substrates, numerous types of metalloreceptors may be imagined that would be of interest as abiotic chemical species or as bioinorganic model systems. 

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