Organometallic Chemistry

Background/Motivation

Research in the organometallics subgroup of the Mirkin group focuses on two main areas:

1) understanding the nuances of small-molecule-induced signal transduction processes in coordination-based complexes and supramolecular assemblies, and

2) using coordination-based assembly methodologies to construct abiotic allosteric enzyme mimics. In 1998, we introduced the Weak-Link Approach (WLA) to supramolecular assembly, a new and versatile strategy for preparing a wide range of coordination-based systems.

This WLA takes advantage of hemilabile ligands, that contain both strong and weak binding moieties, that can coordinate to metal centers and quantitatively assemble into a single condensed structure. The WLA yields structures that can be manipulated by exploiting the weaker metal-ligand interactions. For example small ligating molecules (e.g. Cl–, CO, CH3CN, COO–), can be used to selectively break the weak metal-ligand bonds, allowing for the conversion of the condensed structure to an open flexible one (Figure 1). This process constitutes a form of allosteric control, and over the last two decades, we have shown the generality of the WLA for constructing a wide array of allosteric supramolecular structures, that vary in terms of metal centers and, pocket size and shape, and number of possible accessible states.

Figure 1

Construction of flexible structures using the WLA.

Allosteric Enzyme Mimics and Signal Amplification Assembled via the Weak-Link Approach

Allosteric regulation of enzyme activity at the inactive sites often takes place through the binding of a small molecule and/or elemental ion at a secondary site. Unlike other coordination-based assembly methodologies, structures assembled via the WLA have the ability to be chemically interconverted between various conformational states, allowing us to prepare systems reminiscent of allosteric enzymes. Using the WLA, we have prepared the first example of an abiotic, allosterically controllable supramolecular catalyst. A bimetallic Zn(II)-salen macrocyclic complex was constructed where in the closed state the catalyst is ‘off’, however, when activated with the appropriate small molecule effectors, it can be turned ‘on’ to catalyze an acyl transfer reaction.

Furthermore, the ability to use an external stimulus to trigger a catalytic reaction provides the basis for a general strategy for highly amplified chemical detection systems. In an extension of the study based on the Zn(II)-salen macrocyclic systems, we discovered that acetate anions can be detected in a PCR-like fashion (PCR – Polymerase Chain Reaction), resulting in target self-amplification (Figure 2).  In both examples the systems are coupled to fluorescent indicators, whereby a trace amount of analyte activates a catalytic reaction that generates a fluorescent surrogate for the analyte. This general detection scheme has led to highly sensitive detection methods for various small molecule and elemental ion analytes.

Figure 2

Allosteric supramolecular bimetallic Zn(II) catalyst in the context of acetate target self-amplification in a PCR-like cascade reaction.

Halide Induced Ligand Rearrangement (HILR)

Our desire to expand the range of catalytic moieties applicable to WLA architectures prompted the discovery and development of the Halide-Induced Ligand Rearrangement (HILR) reaction, whereby two unique hemilabile ligands can be reacted with a Rh(I) precursor to form the corresponding dissymmetric heteroligated products. We have shown that macrocyclic, tweezer, triple-decker, and other well-defined three-dimensional supramolecular structures can form quantitatively in a “one-pot” synthesis at room temperature. This capability allows one to fine-tune the distances between key structural units within the targeted structures. Work on the Rh(I)-based HILR reaction resulted in the synthesis of an allosteric supramolecular triple-layer catalyst used for the ring-opening polymerization of e-caprolactone.

Using the reversible addition and abstraction of chloride ions, we were able to alter the structure of the complex moving the bulky blocking groups away from the active site, thus exposing and activating the buried catalyst (Figure 3). This work illustrates our ability to introduce a variety of functional groups into a WLA-based triple-layered structure via coordination chemistry, and it is a powerful and potentially general method for synthesizing protected active centers that can be reversibly activated and deactivated in situ without substantial loss of catalytic activity as a result of this cycling.

Figure 3

Triple-layer polymerization catalyst synthesized via the Weak-Link Approach (WLA) and HILR reaction.

Assembly and Allosteric Regulation of Host-Guest Interactions in Molecular Capsules via the Weak-Link Approach

In order to regulate biological functions such as breathing, protein folding and signal transduction, enzymes and proteins have evolved advanced active pockets capable of binding substrates with high affinity and specificity. Furthermore, many of these biological hosts will, upon the introduction of an allosteric effector, dramatically change the binding properties of the host structure enabling the biological entity to reversibly switch between one or more configurations. The unique capability of enzymes to allosterically regulate host-guest properties, allows for the existence of complex biological cycles and ensures the realization of homeostasis in organisms. Inspired by the ability of certain enzymatic binding pockets to reversibly switch between multiple guest-binding configurations, we have designed a multi-state allosterically regulated molecular receptor.

In this example, chemical effectors are used to modulate the coordination state of a Pt(II) metal center, which dictates the overall charge and size of the calix[4]arene-based binding pocket in the molecular receptor (Figure 4). Overall, three configurations are accessible via the weak-link approach: a closed, inactive configuration and two active configurations, semi-open and fully open. Only in the active configurations is the formation of host-guest complexes possible since the binding pocket in the closed configuration has completely collapsed. On the other hand, guest selectivity in the active configurations, is achieved by controlling the charge and intermolecular interactions between the semi-open and fully open configurations.

Finally, reversibility between the different binding configurations is easily achieved in situ by the simple addition or abstraction of elemental anions from solution. This reversibility allows different guests to occupy the cavity of the molecular receptor. Overall, this work shows how the WLA can be used to assemble biomimetic supramolecular host architectures guest-binding properties that can be modulated in a manner reminiscent to those seen in biological systems.

Figure 4

Modulation of host-guest properties in a three-state allosteric molecular receptor via the Weak-Link Approach.

Allosteric Regulation of Photoredox Catalysts and Photochemical Transformations via the Weak-Link Approach

In Nature, light harvesting is allosterically regulated via conformational and electronic changes on the photosynthetic antenna protein complexes. The allosteric regulation of Photosystem II is important for preventing damage to biological machinery due to overexposure to sunlight and to keep the concentration of ions at healthy levels. Although there is a large number of photoredox complexes, fundamental limitations in current approaches to regulating inorganic light-harvesting mimics, prevents their application in fields such as catalysis. Here, we show that a light-harvesting antenna/reaction biomimic can be regulated by utilizing a coordination framework incorporating antenna hemilabile ligands that was assembled via the WLA (Figure 5).

Allosteric regulation is afforded by coupling the conformational changes to the disruptions in the electrochemical landscape of the Rh(I) and organic framework upon recognition of small molecule effectors. The hemilabile ligands enable switching using redox-inactive inputs, such as chloride anions, allowing one to regulate the photoredox catalytic activity of the photosynthetic mimic reversibly and in situ. This assembly shows that bioinspired regulatory structures assembled via the WLA can be utilized as inorganic light-harvesting arrays that display switchable catalytic properties, with potential uses in solar energy conversion and photonic devices.

Figure 5

Regulation of a bioinspired light-harvesting antenna mimic via the Weak-Link Approach. Photocatalytic behavior is controlled via coordination chemistry at a distal, redox-active Rh(I) center. The light-harvesting antenna is shown in green, and the photoredox center is shown in magenta and blue.

Allosteric Regulation of Supramolecular Hydrogen-Bonding Oligomers and Catalytic Activity via the Weak-Link Approach

In this example, we demonstrate that the activity of a hydrogen-bond-donating (HBD) catalyst embedded within a coordination framework can be allosterically regulated in situ by controlling oligomerization via simple changes in coordination chemistry at distal Pt(II) nodes (Figure 6). Using the halide-induced ligand rearrangement reaction (HILR), a heteroligated Pt(II) triple-decker complex can be formed, which contains a catalytically active diphenylene squaramide moiety and two hydrogen-bond-accepting (HBA) ester moieties. Due to the hemilabile nature of the ligands, the resulting complex can be interconverted between a flexible, semi-open state and a rigid, fully closed state in situ and reversibly. FT-IR spectroscopy, 1H DOSY, and 1H NMR spectroscopy titration studies were used to demonstrate that, in the semi-open state, intermolecular hydrogen-bonding between the HBD and HBA moieties drives oligomerization of the complex and prevents substrate recognition by the catalyst.

In the rigid, fully closed state, these interactions are prevented by steric and geometric constraints. Thus, the diphenylene squaramide moiety is able to catalyze a Friedel–Crafts reaction in the fully closed state, while the semi-open state shows no reactivity. This work shows that controlling catalytic activity by regulating aggregation through supramolecular conformational changes, a common process observed in living systems, can be applied to abiotic catalytic frameworks that are relevant to materials synthesis, as well as the detection and amplification of small molecules.

Figure 6

Allosteric regulation of a catalytic squaramide-based triple-decker complex via the Weak-Link Approach. In the flexible semi-open state, self-association via a hydrogen-bond network prevents the squaramide from engaging in catalytic activity. Meanwhile, the rigid conformation of the closed state prevents the formation of oligomers, allowing the substrate to bind the squaramide and initiate the catalytic cycle.

Organometallic Subgroup Members

Standing (L-R): Andy Wang, Yuan Liu, David Walker, Kacper Sjakuj, Yashin Manraj, Ho Cheng, Oliver Hayes, Ashlee Robison

Sitting (L-R): EunBi Oh, Andrea D’Aquino (leader), Lam-Kiu Fong, Janet McMillan