TRIPODAL TRISAMIDES BASED ON NICOTINIC AND PICOLINIC-ACID DERIVATIVES

A number of polydentate arylamide ligands have been prepared by coupli ng various acyclic tripodal or linear polyamines with derivatives of n icotinic and picolinic acids. Two synthetic procedures were utilized; tris {[(2-hydroxynicotinyl)carbonyl]-2-aminoethyl} (H3NICTREN) was pre pared by Method A, the HOSu/DCC method, and the other arylamides in th is study were prepared by Method B, the CDI method. Method A involved the reaction of N-hydroxysuccinimide with 2-hydroxynicotinic acid (in the presence of dicyclohexylcarbodiimide (DCC) as a dehydrative coupli ng reagent) to form the succinimide ester, followed by reaction with T REN to yield H3NICTREN. Method B involved reaction of a carboxylic aci d (2-hydroxynicotinic, 3-hydroxypicolinic, nicotinic, or picolinic aci ds) with carbonyldiimidazole (CDI) to form the N-acylimidazolide, foll owed by reaction with the amine (TREN, TAME, spermidine, or TRPN) to y ield the desired arylamide. The X-ray structure of 1,1,1-tris{[(3 -hyd roxypicolinyl) carbonyl] -2-aminomethyl} ethane (H3PICTBME) was determ ined; crystals of H(3)PICTAME are monoclinic, a = 10.257(2), b = 15.57 2(3), c = 15.208(2) Angstrom, beta = 96.124(15)degrees, Z= 4, space gr oup P2(1)/a. The structure was solved by direct methods and refined by full-matrix least-squares procedures to R = 0.041 and R-w = 0.038 for 2506 reflections with I greater than or equal to 3 sigma(I). In the s olid state, H(3)PICTAME contains an extensive hydrogen-bonding network , with eight intra- and one intermolecular ii-bonds per molecule; the ligand is partially preorganized for metal ion chelation. The acid dis sociation constants of H3NICTREN and those of 1,1,1-tris { [(2-hydroxy nicotinyl)carbonyl]-2-aminomethyl} (H(3)NICTAME) have been determined; pK(a1) = 11.2 (10.68), pK(a2) = 10.7 (10.58), pK(a3) = 10.0 (9.71), a nd pK(a3) = 6.25 for H3NICTREN (H(3)NICTAME); the high phenolic pK(a)' s are consistent with the hydrogen bonding observed in the solid state .