Chromogenic Detection of the Organophosphorus Nerve Agent Simulant DCP Mediated by Rhodium(II,II) Paddlewheel Complexes.

Organophosphorus nerve agents (OPNAs) pose a great threat to humanity. Possessing extreme toxicity, rapid lethality, and an unassuming appearance, these chemical warfare agents must be quickly and selectively identified so that treatment can be administered to those affected. Chromogenic detection is the most convenient form of OPNA detection, but current methods suffer from false positives. Here, nitrogenous base adducts of dirhodium(II,II) acetate were synthesized and used as chromogenic detectors of diethyl chlorophosphate (DCP), an OPNA simulant. UV-vis spectrophotometry was used to evaluate the sensitivity and selectivity of the complexes in the detection of DCP. Visual limits of detection (LOD) for DCP were as low as 1.5 mM DCP, while UV-vis-based LODs were as low as 0.113 µM. The dirhodium(II,II) complexes were also tested with several potential interferents, none of which produced a visual color change that could be mistaken for OPNA response. Ultimately, the Rh2(OAc)4(1,8-diazabicyclo[5.4.0]undec-7-ene)2 complex showed the best combination of detection capability and interferent resistance. These results, when taken together, show that dirhodium(II,II) paddlewheel complexes with nitrogenous base adducts can produce instant, selective, and sensitive detection of DCP. It is our aim to further explore and apply this new motif to produce even more capable OPNA sensors.

Rh(II)-Catalyzed Si-H Insertion with Nosyl-hydrazone-Protected Aryl Donor Diazo Compounds.

Dirhodium(II,II) paddlewheel catalysts were evaluated in silyl-hydrogen insertion reactions of aryl diazo compounds generated from o-nosyl hydrazones. The high reactivity of aryl diazo compounds necessitates their in situ generation from sulfonyl-protected hydrazones. Herein, we describe our efforts to evaluate this transformation utilizing Rh(II) catalysts, including those with tethered, axially coordinating ligands. The heteroleptic catalyst, Rh2(OAc)3(2-OX), provided the highest yield of silanes when dioxane was the solvent.

Effect of Tethered, Axially Coordinated Ligands (TACLs) on Dirhodium(II,II) Catalyzed Cyclopropanation: A Linear Free Energy Relationship Study.

Hammett correlation experiments were used to determine the influence of dirhodium(II,II) paddlewheel complexes with tethered, axially coordinated ligands (TACLs) on the selectivity of rhodium carbenoids in competitive cyclopropanation reactions. The results suggest that dirhodium(II,II) paddlewheel complexes with TACLs are less sensitive to changes in electronics and reduce selectivity in cyclopropanation reactions with acceptor-substituted rhodium carbenoids. Also, Hammett plots with aryl diazoacetates resulted in a nonlinear downward curvature, suggesting a change in the rate-limiting step of the carbene transfer reaction.

Heteroleptic dirhodium(II,II) paddlewheel complexes as carbene transfer catalysts.

This review highlights the applications of dirhodium(II,II) paddlewheel complexes with a heteroleptic scaffold. Dirhodium(II,II) paddlewheel complexes are well known as highly efficient and selective carbene transfer catalysts. While the majority of described complexes are homoleptic, comparatively fewer studies have concerned heteroleptic complexes. Here, we emphasise the use of heteroleptic complexes in order to highlight their benefits as carbene transfer catalysts and spur future research. Methods to synthesise heteroleptic dirhodium(II,II) paddlewheel complexes are discussed as well as a categorical review of their types of heteroleptic complexes and the carbene reactions in which they have been used.

Tuning Rh(II)-catalysed cyclopropanation with tethered thioether ligands.

Dirhodium(ii) paddlewheel complexes have high utility in diazo-mediated cyclopropanation reactions and ethyl diazoacetate is one of the most commonly used diazo compounds in this reaction. In this study, we report our efforts to use tethered thioether ligands to tune the reactivity of RhII-carbene mediated cyclopropanation of olefins with ethyl diazoacetate. Microwave methods enabled the synthesis of a family of RhII complexes in which tethered thioether moieties were coordinated to axial sites of the complex. Different tether lengths and thioether substituents were screened to optimise cyclopropane yields and minimise side product formation. Furthermore, good yields were obtained when equimolar diazo and olefin were used. Structural and spectroscopic investigation revealed that tethered thioethers changed the electronic structure of the rhodium core, which was instrumental in the performance of the catalysts. Computational modelling of the catalysts provided further support that the tethered thioethers were responsible for increased yields.

Synthesis and Catalytic Properties of Dirhodium Paddlewheel Complexes with Tethered, Axially Coordinating Thioether Ligands.

Novel mixed-ligand rhodium(II) paddlewheel complexes incorporating tethered axial thioether ligands have been synthesized and characterized. The thioether moiety is essential for high yields and the suppression of byproducts in cyclopropanation reactions using an electron-deficient diazoacetate. Crystal structures, UV-vis analysis, and cyclic voltammetry experiments shed light on the catalytic performance of the complexes.

Large-Scale Flow Photochemical Synthesis of Functionalized trans-Cyclooctenes Using Sulfonated Silica Gel.

Functionalized trans-cyclooctenes are useful bioorthogonal reagents that are typically prepared using a flow photoisomerization method where the product is captured by AgNO3 on silica gel. While this method is effective, the leaching of silver can be problematic when scaling up syntheses. It is shown here that Ag(I) immobilized on tosic silica gel can be used to capture trans-cyclooctene products at higher loadings without leaching. It is demonstrated that the sulfonated silica gel can be regenerated and reused with similar yields over multiple runs. Nine different trans-cyclooctenes were synthesized, including those commonly utilized in bioorthogonal chemistry as well as new amine and carboxylic acid derivatives.

Conformationally Strained trans-Cyclooctene with Improved Stability and Excellent Reactivity in Tetrazine Ligation.

Computation has guided the design of conformationally-strained dioxolane-fused trans-cyclooctene (d-TCO) derivatives that display excellent reactivity in the tetrazine ligation. A water soluble derivative of 3,6-dipyridyl-s-tetrazine reacts with d-TCO with a second order rate k2 366,000 (+/- 15,000) M-1s-1 at 25 °C in pure water. Furthermore, d-TCO derivatives can be prepared easily, are accessed through diastereoselective synthesis, and are typically crystalline bench-stable solids that are stable in aqueous solution, blood serum, or in the presence of thiols in buffered solution. GFP with a genetically encoded tetrazine-containing amino acid was site-specifically labelled in vivo by a d-TCO derivative. The fastest bioorthogonal reaction reported to date [k2 3,300,000 (+/- 40,000) M-1s-1 in H2O at 25 °C] is described herein with a cyclopropane-fused trans-cyclooctene. d-TCO derivatives display rates within an order of magnitude of these fastest trans-cyclooctene reagents, and also display enhanced stability and aqueous solubility.