Michael J. Wiester

Enzyme Mimics Based Upon Supramolecular Coordination Chemistry

Recent advances in supramolecular coordination chemistry have allowed chemists to synthesize macromolecular complexes that exhibit various properties intrinsic to enzymes. This Review focuses on structures inspired by properties and functions observed in enzymes rather than precise models of enzyme active sites. These structures are synthesized using convergent, modular, and high-yielding coordination-chemistry-based methods, which allow one to tailor the size, shape, and properties of the resulting complexes. Many of the structures discussed exhibit reactivity and specificity reminiscent of natural systems, and some of them have functions that exceed the natural systems which provided the inspiration for initially making them.

Heteroligated supramolecular coordination complexes formed via the halide-induced ligand rearrangement reaction.

Supramolecular coordination chemistry allows researchers to synthesize higher-order structures that approach the nanoscale dimensions of small enzymes. Frequently, such structures have highly symmetric macrocyclic square or cage shapes. To build functional structures that mimic the complex recognition, catalytic, and allosteric properties of enzymes, researchers must do more than synthesize highly symmetric nanoscale structures. They must also simultaneously incorporate different functionalities into these structures and learn how to regulate their relative arrangement with respect to each other. Designing such heteroligated coordination complexes remains a significant challenge for supramolecular chemists. This Account focuses on the discovery and development of a novel supramolecular reaction known as the halide-induced ligand rearrangement (HILR) reaction. Two hemilabile ligands with different binding strengths combine with d(8) transition metal precursors that contain halide ions. The reaction spontaneously results in heteroligated complexes and is highly modular and general. Indeed, it not only can be used to prepare tweezer complexes but also allows for the rapid and quantitative formation of heteroligated macrocyclic triple-decker/step and rectangular box complexes from a variety of different ligands and transition metal ions. The relative arrangement between functional groups A and B in these structures can be regulated in situ using small ancillary ligands such as halides, CO, and nitriles. Based on this reaction, zinc- and magnesium-porphyrin moieties can be incorporated into heteroligated macrocyclic or tweezer scaffolds. These examples demonstrate the convergent and cofacial assembly of functional sites that are known to be involved in numerous processes in enzymes. They also show how the relative spatial and lateral distances of these sites can be varied, in many cases reversibly. Researchers can use such complexes to study a wide range of enzymatic processes, including catalysis, molecular recognition, electron transfer, and allosteric signal transfer.

A coordination chemistry dichotomy for icosahedral carborane-based ligands

Although the majority of ligands in modern chemistry take advantage of carbon-based substituent effects to tune the sterics and electronics of coordinating moieties, we describe here how icosahedral carboranes-boron-rich clusters-can influence metal-ligand interactions. Using a series of phosphine-thioether chelating ligands featuring meta- or ortho-carboranes grafted on the sulfur atom, we were able to tune the lability of the platinum-sulfur interaction of platinum(II)-thioether complexes. Experimental observations, supported by computational work, show that icosahedral carboranes can act either as strong electron-withdrawing ligands or electron-donating moieties (similar to aryl- or alkyl-based groups, respectively), depending on which atom of the carborane cage is attached to the thioether moiety. These and similar results with carborane-selenol derivatives suggest that, in contrast to carbon-based ligands, icosahedral carboranes exhibit a significant dichotomy in their coordination chemistry, and can be used as a versatile class of electronically tunable building blocks for various ligand platforms.

Spectroscopic Tracking of Molecular Transport Junctions Generated by Using Click Chemistry

Click to fill the gap: The in situ modular fabrication of molecular transport junctions in nanogaps generated by on-wire lithography is achieved by using click chemistry (see picture). The formation of molecular junctions proceeds in high yields and can be used to test different molecules; the triazole group also maintains conjugation in the molecular wires. Raman spectroscopy is used to characterize the molecular assembly processes.

Inversion of product selectivity in an enzyme-inspired metallosupramolecular tweezer catalyzed epoxidation reaction

This study describes a heteroligated, hemilabile Pt(II)-P,S tweezer coordination complex that combines a chiral Jacobsen-Katsuki Mn(III)-salen epoxidation catalyst with an amidopyridine receptor, which leads to an inversion of the major epoxide product compared to catalysts without a recognition group.

Hybridization-induced "off-on" 19F-NMR signal probe release from DNA-functionalized gold nanoparticles

therapeutic delivery, [ 2 ] imaging, [ 3 ] and applications that combine modalities (i.e., theranostic). [ 4 ] In addition to tracking the location of nanoparticles, [ 5 ] imaging modalities also can be used to detect specifi c molecular interactions within cells by way of nanoparticle-enabled “off–on” switches. [ 6 ] Nucleicacid-functionalized gold nanoparticles (DNA or RNA AuNPs, structures where nucleic acids are covalently attached to gold nanoparticles) [ 7 ] are a promising new gene regulation platform. In addition to exhibiting excellent cell transfection capabilities (over 50 different cell lines), [ 7e ] they can be combined with imaging agents (e.g., gadolinium), allowing researchers to track their location using magnetic resonance imaging (MRI). [ 8 ] AuNPs are also effi cient distancedependent quenchers of molecular fl uorescence, [ 9 ] and have been used to develop a new class of nucleic-acid and smallmolecule probes, which release fl uorescent signaling agents

Solvent and temperature induced switching between structural isomers of Rh(I) phosphinoalkyl thioether (PS) complexes.

To develop functional systems based on the weak-link approach (WLA), it is important to understand how solvent and ligand binding strength alter the coordination geometry of complexes formed from this method. A series of phosphinoalkyl thioether (PS) hemilabile ligands with varying electron donating abilities were synthesized and incorporated into homoligated Rh(I)(PS)2Cl complexes to help understand the effects of solvent and ligand binding strength on the preferred coordination modes. The switching between closed and semiopen structural isomers of these Rh(I)(PS)2Cl complexes was studied by variable temperature 31P NMR spectroscopy in different solvent mixtures of CH2Cl2 and tetrahydrofuran (THF) to obtain thermodynamic parameters (DeltaG(o), DeltaH(o), TDeltaS(o), and K(eq)). The isomers differ in the position of the chloride counterion. In the closed isomer, the Cl- anion occupies the outer coordination sphere, while in the semiopen isomer, the Cl- has moved inner sphere and displaced one of the Rh-S bonds. The closed isomer is favored in CH2Cl2 and the semiopen isomer is favored in THF. The preference for either isomer at equilibrium depends on the solvent polarity, based upon the E(T)(N) solvent polarity scale, as was determined from 15 different solvents, with more polar solvents favoring the closed isomer. The isomer preference also depends on the electron donating ability of the group attached to the sulfur of the PS ligand, with electron donating groups favoring the closed isomers and electron withdrawing groups favoring the semiopen isomers. The formation of the semiopen isomer from the closed isomer is entropically favored but enthalpically disfavored under all conditions studied. Elucidation of the principles and environments that determine the equilibrium between the two isomers will aid in the design of functional complexes prepared by the WLA.

Elucidating the mechanism of the halide-induced ligand rearrangement reaction

The formation of heteroligated Rh(I) complexes containing two different hemilabile phosphinoalkyl ligands, (κ(2)-Ph(2)PCH(2)CH(2)S-Aryl)(κ(1)-Ph(2)PCH(2)CH(2)O-C(6)H(5))RhCl, through a halide-induced ligand rearrangement (HILR) reaction has been studied mechanistically. The half-life of this rearrangement reaction depends heavily on the Rh(I) precursor used and the chelating ability of the phosphinoalkyl thioether (PS) ligand, while the chelating ability of the phosphinoalkyl ether (PO) ligand has less of an effect. An intermediate complex which contains two PO ligands, (nbd)(κ(1)-Ph(2)PCH(2)CH(2)O-C(6)H(5))(2)RhCl (nbd = norbornadiene), converts to (nbd)(κ(1)-Ph(2)PCH(2)CH(2)O-C(6)H(5))RhCl resulting in a free PO ligand. The free PO ligand can then react with a homoligated PS complex [(κ(2)-Ph(2)PCH(2)CH(2)S-Aryl)(2)Rh](+)Cl(-) producing the heteroligated product. The PS ligand generated during the reaction pathway can be trapped by the monoligated PO complex (nbd)(κ(1)-Ph(2)PCH(2)CH(2)O-C(6)H(5))RhCl, leading to the formation of the same heteroligated product. In this study, some of the key intermediates and reaction steps underlying the HILR reaction have been identified by variable temperature (31)P{(1)H} NMR spectroscopy and in two cases by single-crystal X-ray diffraction studies. Significantly, this work provides mechanistic insight into the HILR process, which is a key reaction used to prepare a large class of highly sophisticated three-dimensional metallosupramolecular architectures and allosteric catalysts.

Water-Soluble Macrocycles Synthesized via the Weak-Link Approach

We report a general, high-yielding method for the synthesis of water-soluble complexes, which is based upon the weak-link approach to supramolecular coordination chemistry. Specifically, we have utilized oligomeric ethylene glycol functional groups appended to the aryl groups of the diphenylphosphine moieties to achieve solubility. Small molecules or halide ions can be used to expand these complexes into larger, more flexible macrocyclic structures. The realization of this approach should allow for the preparation of allosteric biomimetic structures which can be used in aqueous media.