Ferric ion-specific sequestering agents. 7. Synthesis, iron-exchange kinetics, and stability constants of n-substituted, sulfonated catechoylamide analogues of enterobactin

Journal Article · Wed Aug 26 00:00:00 EDT 1981 · J. Am. Chem. Soc.; (United States)

DOI:https://doi.org/10.1021/ja00407a030· OSTI ID:5896855

Pecoraro, V L; Weitl, F L; Raymond, K N

Two analogues of enterobactin are reported which exhibit (i) stability to base-catalyzed hydrolysis of the central ring, (ii) water solubility, and (iii) N-substitution to block peptidase hydrolysis of the amide bonds. The first compound 1,3,5-tris(N-methyl-N-(2,3-dihydroxysulfobenzoyl)aminomethyl)benzene (Me/sub 3/MECAMS) was prepared, via the amide of trimesoyl chloride and MeNH/sub 2/, in four steps and 6% overall yield. The proton-dependent formation constant (log K* = log ((FeL/sup 6 -/)(H/sup +/)/sup 3/)/((Fe/sup 3 +/)(H/sub 3/L/sup 6 -/))) is 5.21, which gives an equilibrium concentration of (Fe/sup 3 +/) at pH 7.4 x 1 x 10/sup -27/ M for 10/sup -5/ M Me/sub 3/MECAMS and 10/sup -6/M total Fe/sup 3 +/. Me/sub 3/MECAMS (6.0 mM) removed 3.7% of the ferric iron initially sequestered by the iron-storage protein ferritin after 6 h. The human iron-transport protein transferrin releases iron to Me/sub 3/MECAMS with a pseudo-first-order rate constant of 1.9 x 10/sup -3/ min/sup -1/ (ligand concentration 2 x 10/sup -4/ M, T = 25/sup 0/C, ..mu.. = 0.10 M). Two related compounds have been prepared in which the catechol ring is attached to the amide nitrogen through a methylene group. In 1,3,5-tris(N-acetyl-N-(2,3-dihydroxysulfobenzyl)aminomethyl)benzene (NAcMECAMS) and its unsulfonated precursor, the amide linkage of the catechoyl amides such as Me/sub 3/MECAMS has been shifted from an endo position relative to the benzene and catechol rings to an exo position in which the amide carbonyl is not conjugated with the catechol ring and cannot form a stable chelate ring in conjunction with a catechol oxygen. As a result of the removal of the carbonyl group from conjugation with the catechol ring, the acidity of NAcMECAMS is less than Me/sub 3/MECAMS. While the estimated log ..beta../sub 110/ = 40 is approximately the same as for the Me/sub 3/MECAMS, the effective formation constant (log K*) and pM (-log(Fe/sub aq//sup 3 +/)) values are lower (4.0 and 25.0, respectively).

• Research Organization: Univ. of California, Berkeley
• DOE Contract Number: W-7405-ENG-48
• OSTI ID: 5896855
• Journal Information: J. Am. Chem. Soc.; (United States), Journal Name: J. Am. Chem. Soc.; (United States) Vol. 103:17; ISSN JACSA
• Country of Publication: United States
• Language: English

Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
400301* -- Organic Chemistry-- Chemical & Physicochemical Properties-- (-1987)
AMIDES
CHEMICAL PREPARATION
CHEMICAL REACTIONS
COMPLEXES
DECOMPOSITION
ENZYMES
HYDROLYSIS
IRON COMPLEXES
LYSIS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
SOLVOLYSIS
STABILITY
SYNTHESIS
TRANSITION ELEMENT COMPLEXES