Synthesis of novel pendant arm macrocyclic ligands as potential models for enterobactin




Cameron, Beth

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A series of pendant arm tris-catecholate macrocyclic ligands were synthesized. The first, based on 1,4,7- triaminopropyl-1, 4, 7-triazacyclononane, was prepared via condensation with 2,3-dimethoxybenzoyl chloride. The deprotection of the catechol moieties was achieved with boron tribromide in 80% yields. The ferric complexes were characterized by electronic absorption spectroscopy. The second series of ligands described are based on the pendant arm macrocyclic ligand, 1, 4, 7-triaminoethyl-1, 4, 7- triazacyclononane. New routes to the preparation of this ligand were investigated; the best approach used chloroacetyl chloride as the reagent in functionalizing the nitrogen atoms of the triazacyclononane ring. The ligands, 1, 4, 7-tris-((2, 3- dihydroxyphenethyl) aminoethyl)-1, 4, 7-triazacyclononane (34) and 1, 4, 7-tris-((2, 3-dihydroxybenzyl)aminoethyl)-1, 4, 7- triazacyclononane (36) were prepared through a series of acid chloride condensation reactions, followed by reduction of the amides with diborane. The mononuclear ferric complexes of compounds 34 and 36 Were prepared and characterized by uv-visible spectroscopy. Mononuclear nickel, cobalt, and copper complexes of these ligands were also characterized by uv-visible spectroscopy. The binuclear complexes, Na[NiFe(34)] and Na[NiFe(36)], were prepared and characterized by electronic absorption spectroscopy. Tris-((2, 3-dihydroxybenzylamino)ethyl) amine, tris-((2, 3- dihydroxybenzoyl)aminoethyl)amine, and tris-((2 ,3-dihydroxyphenethyl)aminoethyl)amine were prepared by Schiff base condensation reactions, or acid chloride condensation of tris-(2-aminoethyl)amine and the appropriate catecholate moiety. The ferric complexes of these ligands were prepared and characterized by uv-visible spectroscopy. The A1(III) tris-((2,3-dihydroxybenzyl)aminoethyl)amine complex was examined by nmr spectroscopy. The Ni(II), Cu(Il) and Co(III) complexes were investigated by electronic absorption spectroscopy. The rates of base hydrolysis of [Co(tacn) (en)Cl]2+ (tacn=1, 4, 7-triazacyclononane), [Co(tacn) (amp)Cl]2+ (amp=2- aminomethylpyridine), [Co(tacn) (tn)Cl]2+, ufac-I- [Co(dien) (amp)Cl]2+ (dien=l,4,7-triazaheptane), ufac-Il- [Co (dien) (amp)]2+ and [Co (bicycloN5) C1]2+ (bicycloN5=1, 5, 8, 12, 15-pentaazabicyclo [10.5.2] nonadecane), were measured using stopped flow techniques. The base hydrolysis rates (kCH, M-1s-1; [ionic strength (M)]) are 9.66 [0.1], 154 [0.1], 40.6 [0.1], 334 [0.1], 762 [0.1], and 3X103 [1.0], respectively. The rate of [NCS-] anation of [Co (bicycloN5) (OH2)]3+, and the rates of [Br-] and [NCS-] anation of [Co (tacn) (en) (OH2)]3+ were measured as a function of pH. The pKa of the coordinated water molecules are 3.8 ([Co (bicycloN5) (OH2)]3+) and 6.5 ((Co(tacn) (en) (OH2)]3+) . The anation rates increase as the pH increases, indicating a base catalysed anation reaction through the deprotonation of the coordinated amine. In the case of the [Co(tacn) (en) (OH2)]3+ complex, the rate increases as the pH increases until the pH ~ 7, then there is no reaction after that point, suggesting some sort of blockage at the five-coordinate intermediate.



Macrocyclic compounds, Ligands