S. DYQERT, G. MUZII,AND H. SAROFF
2016
The Ionization of Clusters. I. The Dicarboxylic Acids by S. L. Dygert, Giovanna Muzii,’ and H. A. Saroff National Institute of Arthritis and Metabolic Diseases, National Institutes of Health, Public Health Service, U.8. Department of Health, Education and Welfare, Bethesda, Maryland 90014 (Received June SO, 1969)
A method for extracting values for the intramolecular hydrogen bonding constants and the factor E (“electrostatic factor”) for symmetrical dicarboxylic acids is presented. This method is applied to several series of symmetrical dicarboxylic acids from the literature. The structural factors correlated with changes in E and the intramolecular hydrogen-bonding constants are pointed out. It is concluded that large values of K1/4Kz (over 300) usually indicate intramolecular hydrogen bonding, and that it is possible for a strong intramolecular hydrogen bond to exist in aqueous solution. Sodium binding to malonic acid is found to be approximately equal to the binding of sodium to diethylmalonic acid. This contrasts with the much stronger intramolecular hydrogen bond found for the diethyl derivative as compared to malonic acid.
Studies on the binding of hydrogen and other ions to proteins have resulted in a number of interpretations invoking localized interactions between charged sites on protein molecules. I n the case of serum alburninj2 @-lact~globulin,~~ and myosin,8bpairing of carboxylate and ammonium ions was invoked. I n ribon~clease,~ clusters of positive charges interacted with both internal carboxylate ions and other anions in solution. Such clustering of positive and negative charges was demonstrated in the models constructed from the X-ray data for both ribonuclease5 and ribonuclease-
s
.6
In this communication we consider, as a possible model for the Clustering of charged groups in proteins, the symmetrical dicarboxylic acids. The model includes charge effects and intramolecular hydrogen bonding. A technique for evaluating the charge effect and hydrogen-bonding constants is presented and the implications of the analysis are discussed.
1. Explanation of Model Ratios of the two macroscopic association constants for the malonic acids and other symmetrical dibasic acids have been the subject of considerable study emphasizing both charge eff ects7 and the intramolecular hydrogen bond.8 The model considered in this paper includes both hydrogen bonding and the effect of the charge of the neighboring carboxyl group (factor E ) on the hydrogen ion association constant. Consider the reactions in eq 1, The microscopic association constants (eq 2-5) can be defined from this scheme, where brackets refer t o activities.
(3) (4) The Journal of Physical Chemistry
9
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