Intermolecular forces, steric

Simon, Z. (1974). Specific Interactions. Intermolecular Forces, Steric Requirements, and Molecular Size. Angew.Chem.Int.Ed.Engl., 13,719-727. 

Simon, Z. (1974) Specific interactions. Intermolecular forces, steric requirements, and molecular size. Angew. Chem. Int. Ed. Engl, 13, 1V3-1T]. 

Studies of the molar volumes of perdeuteriated organic compounds might be expected to be informative about non-bonded intermolecular forces and their manifestations, and such studies might be considered to obviate the necessity of investigating steric isotope effects in reacting systems. The results from non-reacting systems could then be simply applied to the initial and transition states in order to account for a kinetic steric isotope effect. 

The nature of intermolecular force is essentially no different from that which participates in the chemical bond or chemical reaction. The factor which determines the stable shape of a molecule, the influence on the reaction of an atom or group which does not take any direct part in the reaction, and various other sterically controlling factors might also be comprehended by a consideration based on the same theoretical foundation. 

The dimerisation energy for derivatives of 2 (ca. 35 kJ mol-1) is considerable, particularly in relation to the strength of intermolecular forces and some persistence is required in order to isolate derivatives of 2 which do not form 7T —7r dimers in the solid state. A survey of the monomeric derivatives has been published recently.26 Since the spin density distribution in 2 is rather insensitive to chemical tuning, approaches to inhibit dimerisation rely exclusively on structural modifications, which affect the nature of the intermolecular forces. Inclusion of sterically demanding groups, such as 13, 14 and 15 has proved partially successful (in the case of the diradical 14 one ring is involved in formation of a dimer, while the other retains its open shell character). 

Electrical effects are the major factor in chemical reactivities and physical properties. Intermolecular forces are usually the major factor in bioactivities. Either electrical effects or intermolecular forces may be the predominant factor in chemical properties. Steric effects only occur when the substituent and the active site are in close proximity to each other and even then rarely account for more than twenty-five percent of the overall substituent effect. 

Examples of the application of correlation analysis to diene and polyene data sets are considered below. Both data sets in which the diene or polyene is directly substituted and those in which a phenylene lies between the substituent and diene or polyene group have been considered. In that best of all possible worlds known only to Voltaire s Dr. Pangloss, all data sets have a sufficient number of substituents and cover a wide enough range of substituent electronic demand, steric effect and intermolecular forces to provide a clear, reliable description of structural effects on the property of interest. In the real world this is not often the case. We will therefore try to demonstrate how the maximum amount of information can be extracted from small data sets. 

The use of sterlo parameters such as and of methods such as the branching equations to represent sterlo effects on bio-activity Is Justified. Transport parameters are composite they are a function of differences In Intermolecular forces. The function of bulk and area parameters Is to provide the proper mix of Intennol-eoular forces required by a particular mode of bloaotlvlty. In the absence of parabolic or bilinear behavior bloactlv-Ity can be modeled by an equation based on Intermolecular forces and steric effects. 

Structural effects are of three types Electrical effects, steric effects and intermolecular force effects. Each of these types can be subdivided into various contributions. 

In the second step the bas is recognized by the receptor site and the bas-rep complex forms. As was noted above, the complex is generally bonded by inter-molecular forces. The bas is transferred from an aqueous phase to the receptor site. The receptor site is very much more hydrophobic than is the aqueous phase. It follows, then, that complex formation depends on the difference in intermolecular forces between the bas-aqueous phase and the bas-receptor site. The importance of a good fit between bas and receptor site has been known for many years. The configuration and conformation of the bas can be of enormous importance. Also important is the nature of the receptor. If the receptor is. a cleft, as is the case in some enzymes, steric effects may be maximal as it may not be possible for a substituent to relieve steric strain by rotating into a more favorable conformation. In such a system, more than one steric parameter will very likely be required in order to account for steric effects in different directions. Alternatively, the receptor may resemble a bowl, or a shallow, fairly flat-bottomed dish. Conceivably it may also be a mound. In a bowl or dish, steric effects are likely to be very different from those in a cleft. Possible examples are shown in Fig. 1, 2, and 3. 

Correlations with MR are so numerous that examples are generally not given here. Abbreviations S, steric B, bulk H, hydrophobicity IMF, intermolecular forces, a) Various examples are given in the reference cited. 

We will find in this section that different electrostatic intermolecular forces, e.g. dipole-dipole, quadrupole-quadrupole, van der Waals, and acceptor-donor interactions contribute to chiral recognition. Most important, however, are hydrogen bonding and steric interactions. 

At any rate, a minimum does represent a situation in which attractions and repulsions are balanced (Brehmer et al. 2000). The nomenclature of these intermolecular interactions is quite variegated and the terms are not always clearly defined or distinguished from one another. Some in common usage include van der Waals interactions, London forces, dipole-dipole interactions (and higher terms), dispersion forces, steric repulsion, hydrogen bonds, charge-transfer interactions (also called donor-acceptor interactions), electrostatic interactions, exchange repulsion forces, etc. 

In general, however, rotation and translation of the molecules are degrees of freedom which are acquired simultaneously on fusion, although sometimes only translational freedom is acquired. This happens, for example, in the case of very long molecules where rotation is prevented by steric factors (anisotropic liquids), and also when the intermolecular forces are powerful and anisotropic as for associated liquids. In these instances the freedom of rotation is achieved progressively as the temperature is raised above the melting point. This is in contrast to spherical molecules which, because of their shape and the symmetry of their force fields, begin to rotate freely in the solid state. 

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