title: Interaction of biotin with Mg-O bonds: bifunctional binding and recognition of biotin and related ligands by the Mg(15-crown-5)2+ unit.
abstract: The interaction between biotin and the macrocyclic magnesium complex Mg(15-crown-5)(Otf)2 (15-crown-5 is 1,4,7,10,13-pentaoxacyclopentadecane, Otf(-) is trifluoromethanesulfonate anion) in solution was studied as a model for metal-biotin interactions that may be important in its speciation and function. Shifts in the solution IR spectrum establish that the interaction is dominated by ligation between the carbonyl oxygen of the ureido ring of biotin and the Mg2+ cation. However, comparative binding studies using NMR spectroscopy and conductivity reveal a substantial enthalpic contribution to binding that arises from interactions between the ureido -NH moiety and the macrocyclic ring. This is interpreted in terms of a weak-to-moderate hydrogen bond formed between the -NH group and an oxygen from the crown, which is simultaneously coordinated to Mg2+. This hypothesis is reinforced by quantitative examination of the binding of N-methylated derivatives of 2-imidazolidone, which shows that N,N'-dimethylation decreases the affinity of Mg(15-crown-5)(Otf)2 for the ligand by 2 orders of magnitude. This can be understood in terms of the structure of Mg(15-crown-5)(Otf)2. It shows a pentagonal bipyramidal coordination geometry where the five equatorial positions are occupied by the macrocyclic oxygen donors. The axial positions are occupied by weakly coordinating Otf(-) anions, which are readily displaced by biotin and related derivatives. The M-O(crown) bond distance ranges from 2.1 to 2.3 A, providing structural complementarity for the 2.2 A C=O...HN- bite distance in the ureido group, which leads to strong interaction. The contribution from hydrogen bonding illustrates the importance of second-shell interactions in the biocoordination chemistry of Mg2+. These can serve to organize cofactor interactions with biomolecules, as was recently demonstrated for a biotin-selective RNA aptamer that depends on a direct biotin-magnesium interaction for recognition of biotin (Nix, J.; Sussman, D.; Wilson, C. J. Mol. Biol. 2000, 296, 1235-1244). These results are significant in the context of the observed magnesium requirement in biotin-dependent carboxylase enzymes, where noncovalent interactions with biotin may be important in its activation toward carboxylation in the first step of biotin-dependent CO2 transfer. The synthetic system presented here also suggests that the Mg-O bond may be considered a constituent design element in the rational preparation of complexes to bind and recognize biotin.
authors.affiliation: Department of Chemistry and Biochemistry, Arizona State University, Box 871604, Tempe, Arizona 85287-1604, USA.
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Sanchez
authors.forename: Mary C
authors.initials: MC
authors.lastname: Gessel
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Groy
authors.forename: M Tyler
authors.initials: MT
authors.lastname: Caudle
mesh_terms: D001710:Biotin / Q000737:chemistry* / Q000378:metabolism; D043844:Crown Ethers; D018360:Crystallography, X-Ray; D004988:Ethers, Cyclic / Q000737:chemistry*; D007700:Kinetics; D008274:Magnesium / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D009942:Organometallic Compounds / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D043844:Crown Ethers; D004988:Ethers, Cyclic; D009942:Organometallic Compounds; C042148:15-crown-5; D001710:Biotin; D008274:Magnesium