A Parameter (S_I) for Shape Similarity between Substituents Its Correlatiown with Specific Molecular Recognition

Abstract

In the course of our study to verify the "similarity recognition hypothesis"the threedimensional shape similarity between interacting groups in reacting molecules is responsible for more specific and precise molecular recognition than would otherwise be achievedwe developed a parameter (S_I), which evaluates the three-dimensional shape similarity between a given substituent and the standard one. The two substituents in question, each being represented by the three-dimensional coordinates of its atoms and their van der Waals radii, are so arranged as to give a maximal overlap. Examination is made as to whether or not the points located with constant spacing are involved in the substituents (Fig.1). The S_I is defined as the ratio of the number of points involved in both of the substituents to that involved in either of them (Eq.5). Oxi dation of a pair of associating thiols ([1] and [2]) each with the recognition site (R¹ or R²) (Eq.1) gives one unsymmetrical [4] and two symmetrical disulfides ([3] and [5]). The selectivity (r, a measure of the degree of molecular recognition) is represented by the logarithmic ratio of the yield of the unsymmetrical disulfide [4] to twice that of the symmetrical disulfide [3] (Eq.6). The r values had good correlation with the S_I values for R¹=n-C₅H₁₁ and R²=i-C₆H₁₃, cyclo-C₆H₁₁, and Ph (Table 4), for R¹ =Ph and R²=cyclo-C₆H₁₁, i-C₆H₁₃, and n-C₆H₁₃ (Fig.4), and for R¹=n-C₄H₉ and R²=n-C_n H_2n+1 (n=2-6) (Fig.5). The selectivity neither depen ds on the difference in reactivity between the thiols ([1]and [2]) nor on solubility differences between the thiols. Furthermore, the order of the r values cannot be explained by the electronic, steric, or hydrophobic effect of the recognition site (R²). These findings support the "similarity recognition hypothesis" men-tioned above.