CHEMICAL PROPERTIES 5 



The distance between the two centers of negative charge in malonate 

 is of importance in the binding to succinate dehydrogenase. Calculation of 

 this distance (using the following values: C — C — C angle = 111.7°; — C — 

 angle = 125.8°; C— C distance = 1.544, and C— distance = 1.273) 

 leads to a value of 3.28 A. Intercharge distances for various dicarboxylates 

 and other compounds known to inhibit succinate dehydrogenase are given 

 in Table 1-1, and these values will be of interest in comparisons of inhibi- 

 tory activity. Dicarboxylic acids with more than one methylene group are 

 flexible and the intercharge distances may vary between the limits of great- 

 est bending and extension of the molecules. As the chain length increases 

 there will be greater tendency for the intercharge distance in the ions to 

 be less than that of the maximal extension, since the electrostatic repulsion 

 will decrease. The mean statistical intercharge distance in the succinate ion 

 will probably be closer to 4.75 A than the contracted distance of 3.81 A. 

 Indeed, it may be calculated that it would require at least 2.3 kcal/mole 

 to bring succinate from the extended to the contracted configuration, 

 using the dielectric constant obtained from D = 6d — 7 (Eq. 1-6-72)*; 

 since the dielectric constant is probably less due to the hydrocarbon groups 

 between the charges, this would be a minimal energy value. The mean 

 intercharge distance in the succinate ion may be estimated as not less than 

 4.20 A (Gane and Ingold, 1931; Eyring, 1932; Westheimer and Shookhoff, 

 1939) and possibly closer to 4.75 A. The glutarate intercharge distance is 

 probably around 5.2 A. These considerations are of importance in comparing 

 the interactions of these substances with the active center of succinate 

 dehydrogenase. It must be remembered that the bound ions are undoubt- 

 edly held in a configuration different from the statistical mean in solution. 

 The flexibility of the higher homologs allows them to adjust to a specified 

 configuration, but at the expense of the energy and entropy changes neces- 

 sary to bring them from their free configurations. 



Acidic Ionization 



The ionizations of malonic and succinic acids are important in the inter- 

 actions with succinate dehydrogenase and with regard to the penetration of 

 these substances into cells. The pKJs for the simple dicarboxylic acids, in- 

 cluding various derivatives of succinate and malonate, and related succinic 

 dehydrogenase inhibitors, are given in Table 1-2. The dissociation constants 

 change slightly with ionic strength; for malonic acid, dpK^ Ids = — 0.32, 

 and dpK^ jds = — 0.98, for ionic strengths around 0.15, where s is the 



* In cross references of this type, Eq. 1-6-72, the roman number indicates the volume 

 of this treatise in which the equation, table, or figure (as the case may be) may be 

 found, the first arabic number indicates the chapter number, and the second arabic 

 jiumber the equation, table, or figure number. 



