Linear free energy relationship general discussion

For further discussion we will suppose that the solid catalyst enters in the same reaction of various structurally related compounds precisely as the same agent. The reason for this is lack of support for the opposite and necessity to simplify our treatment. If this is an approximation it seems to be an acceptable one because general conditions for the linear free-energy relationships require small structural changes within the series of compared substances small differences in structure can probably cause only minor alterations in the nature of the catalyst. 

The development of linear free-energy relationships in purely aliphatic molecules is complicated because steric and conformational effects require more consideration than in the case of meta and para aromatic substituents. A number of successful treatments of aliphatic systems have been accomplished by separating polar effects from steric effects. General reviewscan be consulted for discussions of some of these treatments. 

Charge Distribution Calculations Alternative Approaches Force Fields A General Discussion Linear Free Energy Relationships (LFER) Population Analyses for Semiempiri-cal Methods Quantitative Structure-Property Relationships... 

The concept of the similarity of molecules has important ramifications for physical, chemical, and biological systems. Grunwald (7) has recently pointed out the constraints of molecular similarity on linear free energy relations and observed that Their accuracy depends upon the quality of the molecular similarity. The use of quantitative structure-activity relationships (2-6) is based on the assumption that similar molecules have similar properties. Herein we present a general and rigorous definition of molecular structural similarity. Previous research in this field has usually been concerned with sequence comparisons of macromolecules, primarily proteins and nucleic acids (7-9). In addition, there have appeared a number of ad hoc definitions of molecular similarity (10-15), many of which are subsumed in the present work. Difficulties associated with attempting to obtain precise numerical indices for qualitative molecular structural concepts have already been extensively discussed in the literature and will not be reviewed here. 

Nevertheless the general conclusions discussed here, as well as the overall experimental design for their validation, still follow the same unifying trends. For example, linear extrathermodynamic expressions can be proposed between the free energy change of a polypeptide or protein molecule involved in such hydrophobic interactions and particular molecular property parameters %j. This relationship takes the form of... 

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