PNNL

Abstract

We present an extended MM3 model for catecholamide ligands and their Fe3+ complexes and the application of this model to understand how ligand architecture effects Fe3+ binding affinity. Force field parameters were fit to geometries and energies from electronic structure calculations, and to crystal structure data. Optimized geometries are reported for phenol, acetamide, the phenol-phenol dimer, the acetamide-phenol dimer, and N-methylsalicylamide (HMSA) at the BLYP/DZVP2/A2 level of theory. MP2/aug-cc-pVTZ single point energies at the BLYP geometries yield phenol-phenol and acetamide-phenol dimerization energies and relative energy of two HMB conformations. Optimized geometries and relative energies are reported for the psuedo-octahedral ground state and the trigonal planar transition state of [Fe(CAT)3]3- at the VWN/DZVP2/A1 level of theory. VWN/DZVP2/A1 calculations also yielded potential energy surfaces for distortion of Fe-O distances and Fe-O-C-C dihedral angles in this complex. The MM3 model is validated by comparison of calculated structures with crystal structures containing 1,2-dihydroxybenzene (H2CAT) and 2,3-dihydroxy-N-methylbenzamide (H2MBA) fragments, crystal structures of [Fe(CAT)3]3- and tris-catecholamide Fe3+ complexes, and comparison of MM3 (6.8 kcal/mol) and VWN (5.9 kcal/mol) barriers for intramolecular octahedral inversion in [Fe(CAT)3]3-. The MM3 model also rationalizes the higher inversion barrier (14 to 18 kcal/mol) reported for [Ga(N,N-diisopropylterephthalamide)3]3- ([Ga(DIPTA)3]3-). Conformational searches were performed on enterobactin (H6ENT), 1,3,5-tris(2,3-dihydroxybenzamido- methyl)-2,4,6-triethylbenzene (H6EMECAM), 1,3,5-tris(2,3-dihydroxybenzamido- methyl)-2,4,6-trimethyl-benzene (H6MMECAM), 1,3,5-tris(2,3-dihydroxybenzamido- methyl)-benzene (H6MECAM), and 1,5,9-N,N',N''-tris(2,3-dihydroxybenzoyl)-cyclo- triazatridecane (H6-3,3,4-CYCAM) and Fe3+ complexes with each of these ligands...