New 1H-Pyrazole-Containing Polyamine Receptors Able to Complex L-Glutamate in Water at Physiological pH Values

Article abstract of DOI:10.1021/ja035671m

The interaction of the pyrazole-containing macrocyclic receptors 3,6,9,12,13,16,19,22,25,26-decaazatricyclo-[22.2.1.1 ^11,14]-octacosa-1(27),11,14(28),24-tetraene 1[L₁], 13,26-dibenzyl-3,6,9,12,13,16,19,22,25,26-decaazatricyclo-[22.2.1.1 ^11,14]-octacosa-1(27),11,14(28),24-tetraene 2[L₂], 3,9,12,13,16,22,25,26-octaazatricyclo-[22.2.1.1 ^11,14]-octacosa-1(27),11,14(28),24-tetraene 3[L₃], 6,19-dibenzyl-3,6,9,12,13,16,19,22,25,26-decaazatricyclo-[22.2.1.1 ^11,14]-octacosa-1(27),11,14,(28),24-tetraene 4[L₄], 6,19-diphenethyl-3,6,9,12,13,16,19,22,25,26-decaazatricyclo-[22.2.1.1 ^11,14]-octacosa-1(27),11,14(28),24-tetraene 5[L₅], and 6,19-dioctyl-3,6,9,12,13,16,19,22,25,26-decaazatricyclo-[22.2.1.1 ^11,14]-octacosa-1(27),11,14(28),24-tetraene 6[L₆] with L-glutamate in aqueous solution has been studied by potentiometric techniques. The synthesis of receptors 3-6[L₃-L₆] is described for the first time. The potentiometric results show that 4[L₄] containing benzyl groups in the central nitrogens of the polyamine side chains is the receptor displaying the larger interaction at pH 7.4 (K_eff = 2.04 × 10⁴). The presence of phenethyl 5[L₅] or octyl groups 6[L₆] instead of benzyl groups 4[L₄] in the central nitrogens of the chains produces a drastic decrease in the stability [K_eff = 3.51 × 10² (5), K_eff = 3.64 × 10² (6)]. The studies show the relevance of the central polyaminic nitrogen in the interaction with glutamate. 1[L₁] and 2[L₂] with secondary nitrogens in this position present significantly larger interactions than 3[L₃], which lacks an amino group in the center of the chains. The NMR and modeling studies suggest the important contribution of hydrogen bonding and π-cation interaction to adduct formation.