Dicarboxylic acid binding

The 9-coordinate complexes [Ln(DPA)3] (Ln is a general lanthanoid ion and H3DPA is pyridine-2,6-dicarboxylic acid) bind effectively to proteins and can be used as paramagnetic shift reagents for protein NMR spectroscopic studies. The structure of the [La(DPA)3] ion is shown below. 

It is noteworthy that the value of this substrate is smaller by one order compared to non-cyclic compounds. According to the discussions proposed above, this is considered to be due to its conformation already being fixed to the one that fits to the binding site of the enzyme. This estimation was demonstrated to be true by the examination of the effect of temperature on the kinetic parameters. Arrhenius plots of the rate constants of indane dicarboxylic acid and phenyl-malonic acid showed that the activation entropies of these substrates are —27.6 and —38.5 calmol K , respectively. The smaller activation entropy for the cyclic compound demonstrates that the 5yn-periplanar conformation of the substrate resembles the one of the transition state. 

The question arises, whether and to what extent the dicarboxylic acid 1 is capable of binding other solvents besides ethanol (starting observation, cf. Sect. 1) in the crystal lattice. For this purpose, to begin with, crystallization experiments using further alcohols (straight-chain, branched, univalent and polyvalent) were carried out. It was found that 1 is apt to form crystal inclusions on a large scale, i.e. with alcohols of various constitutions. A list of different examples is given in Table 1 (Entries 1-16). 

The hydrolysis of esters by the nickel derivative (271) provided an early example of the use of a metal-capped cyclodextrin as a catalyst (shown here as its p-nitrophenyl acetate inclusion complex) (Breslow Overman, 1970 Breslow, 1971). The synthesis of this host involves the following steps (i) covalent binding of the pyridine dicarboxylic acid moiety to cyclodextrin, (ii) coordination of Ni(n) to this species, and (iii)... 

The actual determination of a correlation function from experimental data depends on the method used to measure the binding constants. The most common method for dicarboxylic acids is from the limiting behaviors at C 0 (the high pH limit) and at C — (the low pH limit). These two limiting behaviors of the BI are (see Section 2.2). 

Perhaps the simplest two-site cooperative systems are small molecules having two binding sites for protons, such as dicarboxylic acids and diamines. Despite their molecular simplicity, most of these molecules do not conform with the modelistic assumptions made in this chapter. Therefore, their theoretical treatment is much more intricate. The main reasons for this are (1) there is, in general, a continuous range of macrostates (2) the direct and indirect correlations are both strong and intertwined, so that factorization of the correlation function is impossible. In addition, as with any real biochemical system, the solvent can have a major effect on the binding properties of these molecules. 

We denote by the first intrinsic binding constant, and by Arj the second intrinsic binding constant. The latter is the same as 1 ,/ i.e., the conditional binding on the second site, given that the first site is occupied. Figure 4.23 shows two alternative, but equivalent, ways of describing the binding of protons to a dicarboxylic acid. 

First and Second Intrinsic Binding Constants (in iiter/moi). Pair Correlations, and Corresponding Work W(l, 1) (in kcal/mol) for o,0[)-Dicarboxylic Acid COOH(CH2) COOH... 

It has been found experimentally [see Edsall and Wyman (1958), p. 485] that the monoester of dicarboxylic acid has a value of the dissociation constant nearly half of the Ki iss value of the dibasic acid. This is equivalent to saying that the binding constant ks to the monoester is nearly the same as the second intrinsic binding constant for the dicarboxylic acid, i.e., kg = k n. 

Table 5.1 presents some values for the intrinsic binding constants, and also pair and triplet correlations for benzoic acid, benzene dicarboxylic acids, and benzene tricarboxylic acids. 

Reaction of the m-nitrophenyl ester of pyridine-2,5-dicarboxylic acid with cyclodextrin (see Section 3) gives a picolinate ester [52] of a cyclodextrin secondary hydroxyl group (Breslow, 1971 Breslow and Overman, 1970) which will bind metal ions or a metal ion-pyridine carboxaldoxime complex. Such a complex will catalyse hydrolysis of p-nitrophenyl acetate bound within the cyclodextrin cavity leading to a rate constant approximately 2000-fold greater at... 

Binding Constants of Protons to Dianions of Dicarboxylic Acids Thermodynamic Functions for Oxygenation of Hemoglobin A Few Well-Known Structural Domains... 

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