Cavity molecular volume

A drawback of the SCRF method is its use of a spherical cavity molecules are rarely exac spherical in shape. However, a spherical representation can be a reasonable first apprc mation to the shape of many molecules. It is also possible to use an ellipsoidal cavity t may be a more appropriate shape for some molecules. For both the spherical and ellipsoi cavities analytical expressions for the first and second derivatives of the energy can derived, so enabling geometry optimisations to be performed efficiently. For these cavil it is necessary to define their size. In the case of a spherical cavity a value for the rad can be calculated from the molecular volume ... 

Tlie molecular volume Vm can in turn be obtained by dividing the molecular weight by density or from refractivity measurements is Avogadro s number. The cavity radius (... 

Molecular volumes are usually computed by a nonquantum mechanical method, which integrates the area inside a van der Waals or Connolly surface of some sort. Alternatively, molecular volume can be determined by choosing an isosurface of the electron density and determining the volume inside of that surface. Thus, one could find the isosurface that contains a certain percentage of the electron density. These properties are important due to their relationship to certain applications, such as determining whether a molecule will fit in the active site of an enzyme, predicting liquid densities, and determining the cavity size for solvation calculations. 

Continuum models of solvation treat the solute microscopically, and the surrounding solvent macroscopically, according to the above principles. The simplest treatment is the Onsager (1936) model, where aspirin in solution would be modelled according to Figure 15.4. The solute is embedded in a spherical cavity, whose radius can be estimated by calculating the molecular volume. A dipole in the solute molecule induces polarization in the solvent continuum, which in turn interacts with the solute dipole, leading to stabilization. 

Leahy, D. E. (1986) Intrinsic molecular volume as a measure of the cavity term in linear solvation energy relationships octanol-water partition coefficients and aqueous solubilities. J. Pharm. Sci. 75, 629-636. 

In the IPCM calculations, the molecule is contained inside a cavity within the polarizable continuum, the size of which is determined by a suitable computed isodensity surface. The size of this cavity corresponds to the molecular volume allowing a simple, yet effective evaluation of the molecular activation volume, which is not based on semi-empirical models, but also does not allow a direct comparison with experimental data as the second solvation sphere is almost completely absent. The volume difference between the precursor complex Be(H20)4(H20)]2+ and the transition structure [Be(H20)5]2+, viz., —4.5A3, represents the activation volume of the reaction. This value can be compared with the value of —6.1 A3 calculated for the corresponding water exchange reaction around Li+, for which we concluded the operation of a limiting associative mechanism. In the present case, both the nature of [Be(H20)5]2+ and the activation volume clearly indicate the operation of an associative interchange mechanism (156). 

We begin with a comparison of the various DO models to each other. Based on a parametric procedure that takes account of the molecular volume encompassed by the 0.001 a.u. electron density envelope, Wong et al. [297] suggested that an appropriate spherical cavity radius is 3.8 A. Szafran et al. [157]... 

In our approach, to estimate the size of the cavity, the solute molecular volume (Vm) is needed. For a spherical cavity the radius is related to the molecular volume (which can be evaluated from the experimental density) according to ... 

As shown in Figure 42 for the Norrish II reactions of a simple ketone, 2-nonanone, not only do the shapes of the products differ from those of the reactant, but so do their molecular volumes [265]. Interestingly, the volume of the fragmentation products, 1-hexene and 2-hydroxypropene (which ketonizes to acetone), are closer in volume to 2-nonanone than is either of the cyclization products. They are also capable of occupying more efficiently the shape allocated by a stiff solvent matrix to a molecule of 2-nonanone in its extended conformation the cross-sectional diameter of either of the cyclobutanols is much larger than that of extended 2-nonanone or the fragmentation products when spaced end-on. Both of these considerations should favor fragmentation processes if isomorphous substitution for the precursor ketone in the reaction cavity is an important requirement for efficient conversion to photoproducts. 

LSER Model of Leahy In the LSER model of Leahy [22], the cavity term is substituted by the molar volume, Vm, at 25°C in g cm-3 or by the intrinsic molecular volume, V), in mLmoL1. The dipolar term and the hydrogen-bonding terms are represented by the dipole moment, n, and the HBA basicity, (3, respectively. Group contribution schemes have been developed to calculate the solvatochromic parameters from molecular structure input [23]. Leahy [22] gives the following equation derived with a diverse set of monofunctional liquids ... 

The correlation between aqueous solubility and molar volume discussed by McAuliffe [5] for hydrocarbons, and the importance of the cavity term in the solvatochromic approach, indicates a significant solubility dependence on the molecular size and shape of solutes. Molecular size and shape parameters frequently used in quantitative structure-water solubility relationships (QSWSRs) are molecular volume and molecular connectivity indices. Moriguchi et al. [33] evaluated the following relationship to estimate Cw of apolar compounds and a variety of derivatives with hydrophilic groups ... 

Leahy, D. E., Intrinsic Molecular Volume as a Measure of the Cavity Term in linear Solvation Energy Relationships Octanol-Water Partition Coefficients and Aqueous Solubilities. J. Pharrn. Sci., 1986 75, 629-636. 

The ratio between the cavity and guest size in terms of their molecular volumes may be expressed in terms of the cavity occupancy factor (p). A p value of 1 represents a completely filled cavity. Occupancy factors for various cryptophanes and guests are shown in Table 6.9. 

A large carcerand has a cavity volume of 120 A3. If the molecular volume of methane is 28.5 A3, calculate the occupancy factor, p, for a 1 1 methane carceplex of this host. What host volume would result in an occupancy factor of 0.67, equivalent to solid methane Calculate the notional pressure of one molecule of methane in a cavity of this size. Do you think that such a carceplex is likely to form ... 

Table 4 Molecular volume of guests (Vg), host cavity (Vc) and PCcavity in the inclusion compounds of CA with monosubstituted benzenes.

A review of this topic is also beyond the scope of this article, but some background is given because some modeling is being used in descriptions of molecular shape, volume, and area. Molecular volume and area calculated by modeling methods are being used particularly in prediction of solubility and partition coefficient. This is because, in any fundamental understanding of these properties, it is necessary to consider the cavity that has to form in water to accommodate the solute. 

Molecular modeling of compounds tested shows molecular volumes similar to those of strigolactones25 and fits into the same hypothetic receptor s cavity. No correlation between the activity and changes in molecular properties such as dipole moments or heat of formation could be established. 

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