Electronic distribution bond indices

Because of intense theoretical work in this area, dynamic aspects of structure such as rotational barriers of methyl substituents and deviations from planarity have been treated in Section 9.01.2.1. For the same reason, calculated heats of formation, total energies, resonance energies, aspects of delocalization and conjugation, homodesmotic stabilization energies, electron distribution, polarizability and magnetic and bond-order-based aromaticity indexes have been discussed in Section 9.01.2.8. Complexation of the parent 1 by water has also been considered (Section 9.01.2.12). 

Figure 1 Depiction of the relationship between molecular structure and therapeutic effect of a medicine. Underlying all the other properties a compound can exhibit arc its 3D disposition of atomic nuclei and the electronic distribution around the nuclei. These inanimate particles of physics determine the chemistry the compound can undergo (reactivity) and its physical properties (density, index of refraction, dipole moment, etc.). The properties, in turn, determine how that molecule will interact with other molecules. The interactions determine solubility, lipophilicity, association, and stability, which affect how well a compound, if administered to a patient, will be transported to its site of action. These interactions will also determine how well the compound will attach to the receptor by first being recognized as complementary to the receptor structure in shape and electronic structure (acidic, basic, and hydrogen bonding groups). The affinity between the compound and the receptor will determine how well a biochemical or conformational change in the receptor will be induced. The latter change must then lead to a cascade of biochemical events that will eventually be observable in the patient in terms of therapeutic response to the drug...

Aromatic substitution reactions are often complicated and multistep processes. A correlation, however, in many cases can be found between the charged attacking species and the electron density distribution in the molecule attacked during electrophilic and nucleoph c substitution. No such correlation is expected in radical substitution where the attacking particles are neutral, rather a correlation between the reactivities of separate bonds and a free valency index of the bond order. This allows the prediction of the most reactive bonds. Such an approach has been used by researchers who applied quantum calculations to estimate the reactivities of the isomeric thienothiophenes and to compare them with thiophene or naphthalene. " Until recently quantum methods for studying reactivities of aromatics and heteroaromatics were developed mainly in the r-electron approximation (see, for example, Streitwieser and Zahradnik ). The M orbitals of a sulfur atom were shown not to contribute substantially to calculations of dipole moments, polarographic reduction potentials, spin-density distribution, ... 

There are two types of solute-solvent interactions which affect absorption and emission spectra. These are universal interaction and specific interaction. The universal interaction is due to the collective influence of the solvent as a dielectric medium and depends on the dielectric constant D and the refractive index n of the solvent. Thus large environmental perturbations may be caused by van der Waals dipolar or ionic fields in solution, liquids and in solids. The van der Waals interactions include (i) London dispersion force, (ii) induced dipole interactions, and (iii) dipole-dipole interactions. These are attractive interactions. The repulsive interactions are primarily derived from exchange forces (non bonded repulsion) as the elctrons of one molecule approach the filled orbitals of the neighbour. If the solute molecule has a dipole moment, it is expected to differ in various electronic energy states because of the differences in charge distribution. In polar solvents dipole-dipole inrteractions are important. 

The summation in Formnla (4.24) can be calculated for all atom pairs or only for all pairs of bonded atoms. The gravitational index is a measure of the spatial distribution of masses in the molecule and is similar to the geometrical principal moments of the inertia descriptor. An electronic index leie is calcnlated with a similar formula... 

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