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

• Published in: Journal of the American Chemical Society Vol. 126; no. 3; pp. 823 - 833
• Main Authors: Miranda, Carlos, Escartí, Francisco, Lamarque, Laurent, Yunta, María J. R, Navarro, Pilar, García-España, Enrique, Jimeno, M. Luisa
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 28.01.2004; Amer Chemical Soc
• Subjects: Biomimetic Materials - chemical synthesis; Biomimetic Materials - chemistry; Chemistry; Chemistry, Multidisciplinary; Glutamic Acid - chemistry; Hydrogen-Ion Concentration; Models, Molecular; Nuclear Magnetic Resonance, Biomolecular; Physical Sciences; Polyamines - chemical synthesis; Polyamines - chemistry; Potentiometry; Pyrazoles - chemical synthesis; Pyrazoles - chemistry; Receptors, Glutamate - chemistry; Science & Technology; Water - chemistry; RECOGNITION; AMINO-ACIDS; SELECTIVE BINDING; FORCE-FIELD; ACETYLCHOLINE-BINDING; PARAMETERS; SIMULATION; MOLECULAR-MECHANICS; DICARBOXYLATE ANIONS; NUCLEIC-ACIDS
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja035671m

The interaction of the pyrazole-containing macrocyclic receptors 3,6,9,12,13,16,19,22,25,26-decaazatricyclo-[22.2.1.111,14]-octacosa-1(27),11,14(28),24-tetraene 1[L 1 ], 13,26-dibenzyl-3,6,9,12,13,16,19,22,25,26-decaazatricyclo-[22.2.1.111,14]-octacosa-1(27),11,14(28),24-tetraene 2[L 2 ], 3,9,12,13,16,22,25,26-octaazatricyclo-[22.2.1.111,14]-octacosa-1(27),11,14(28),24-tetraene 3[L 3 ], 6,19-dibenzyl-3,6,9,12,13,16,19,22,25,26-decaazatricyclo-[22.2.1.111,14]-octacosa-1(27),11,14(28),24-tetraene 4[L 4 ], 6,19-diphenethyl-3,6,9,12,13,16,19,22,25,26-decaazatricyclo-[22.2.1.111,14]-octacosa-1(27),11,14(28),24-tetraene 5[L 5 ], and 6,19-dioctyl-3,6,9,12,13,16,19,22,25,26-decaazatricyclo-[22.2.1.111,14]-octacosa-1(27),11,14(28),24-tetraene 6[L 6 ] with l-glutamate in aqueous solution has been studied by potentiometric techniques. The synthesis of receptors 3−6[L 3 −L 6 ] is described for the first time. The potentiometric results show that 4[L 4 ] 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[L 5 ] or octyl groups 6[L 6 ] instead of benzyl groups 4[L 4 ] 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[L 1 ] and 2[L 2 ] with secondary nitrogens in this position present significantly larger interactions than 3[L 3 ], 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.