Hydrogen Bond Acidity and Basicity

Hydrogen bonds between fluorinated substrates and biological macromolecules have been postulated in some enzyme-substrate complexes. However, it is rather difficult to determine if these hydrogen bonds really exist other factors may stabilize the conformation corresponding to the short H- F interatomic distance observed. Indeed, this conformation can be favored by other factors (e.g., other stronger hydrogen bonds, gauche effect), without participation of an H- F interaction to stabilize the supramolecular structure. The existence and possible 

Compound AGacid (kcal/mol) Compound AGacid (kcal/mol) 

GENERAL REMARKS ON STRUCTURAL, PHYSICAL, AND CHEMICAL PROPERTIES 

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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...

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