In order to study the metal ion binding of optically active p-(2-pyridyl)+ alanine, NH,CH(CH=C, H, N)CO, H, Pyala, and &(6-methyl-2-pyridylla-alanine, NH, CH(CH, C, H, NCH,)CO, H, Mepyala, these pyridine analogs of histidine were synthesized and resolved; absolute configurations were determined for the isolated enatiomers. Protonation constants and formation constants for the binding of L-Pyala, D,L-Pyala, D-Mepyala, and D.L-hiepyala with Cu(II), Ni(II), Co(U), and Zn(II) were determined by potentiometric titration. They show that the formation constant (Rx) for the reaction, M(L-Pyala) + D-Pyala * hW.-Pyala)(D-Pyala), is larger (up to 8.7 times larger) than that <K=) for the coordination of the same enantiomer, M(L-Pyala) f L-Pyala * hi(L-Pyala),. Although the difference between K, and K= cm be explained on a statistical basis for Cu(lI), the larger differences for Ni(II). Co(II), and Zn(I1) demonstrate that their hI(L-Pyala) complexes bind D&ala more favorably than they do L-Pyala. A similar trend was found for the optical isomers of hlepyala except that the stereoselectivity is less than in the Pyala system_ This presumably results from the reduced coordinating abiIity of the 6-methylpyridyl group as compared to the less aowded pyridyi donor. Using ideas previously applied to the analogous histidine system, the observed stereoselectivitier may be explained in terms of the structures of the complexes. * M&A):,, K2 <I) M&A)+ + D-A-* M(L-A) (D-A), K, (2) are different. Gillard et al. 12, 31, Ritsma et al. 141, and Simeon and Weber [S]
found no such stereoselectivity in the coordination of a series of ammo acids with various metal ions. However, with N-benz$proline, the CU(L-A)@-A) complex was found [ 61 to be substantially more stable than Cu(L-A)2 . Several authors [7-l 11 have reported evidence of stereoselectivity in the coordination of histidine by Co(H), Ni(II), Zn(II), and possibly Cu(II).
The tridentate nature of histidine utilizing three different donor groups suggested that other amino acids having this basic structure would also be stereoselective-It was for this reason that we can-led out the synthesis and resolution of &(2-pyridylja-alanine, Pyala, and /I-(6-methyl-%pyridyl)e-alanine, Mepyala: