posted on 2014-09-02, 00:00authored bySimone Bosch, Peter Comba, Lawrence R. Gahan, Gerhard Schenk
It
is becoming increasingly apparent that the secondary coordination
sphere can have a crucial role in determining the functional properties
of biomimetic metal complexes. We have therefore designed and prepared
a variety of ligands as metallo-hydrolase mimics, where hydrogen bonding
in the second coordination sphere is able to influence the structure
of the primary coordination sphere and the substrate binding. The
assessment of a structure–function relationship is based on
derivates of 2,6-bis{[bis(pyridin-2-ylmethyl)amino]methyl}-4-methylphenol
(HBPMP = HL1) and 2-{[bis(pyridin-2-ylmethyl)amino]methyl}-6-{[(2-hydroxybenzyl)(pyridin-2-ylmethyl)amino]methyl}-4-methylphenol
(H2BPBPMP = H2L5), well-known phenolate-based
ligands for metallo-hydrolase mimics. The model systems provide similar
primary coordination spheres but site-specific modifications in the
secondary coordination sphere. Pivaloylamide and amine moieties were
chosen to mimic the secondary coordination sphere of the phosphatase
models, and the four new ligands H3L2, H3L3, HL4, and H4L6 vary in the type and geometric position of the H-bond donors and
acceptors, responsible for the positioning of the substrate and release
of the product molecules. Five dinuclear ZnII complexes
were prepared and structurally characterized in the solid, and four
also in solution. The investigation of the phosphatase activity of
four model complexes illustrates the impact of the H-bonding network:
the Michaelis–Menten constants (catalyst–substrate binding)
for all complexes that support hydrogen bonding are smaller than for
the reference complex, and this generally leads to higher catalytic
efficiency and higher turnover numbers.