Rhodathiaboranes with `anomalous' electron counts: synthesis, structure and reactivity

Analysis of the structures of 8,8-(PPh₃)₂-8,7-nido-RhSB₉H₁₀ and 9,9-(PPh₃)₂-9,7,8-nido-RhC₂B₈H₁₁ by RMS misfit calculations has confirmed that these rhodaheteroboranes possess nido 11-vertex cluster geometries in apparent contravention of Wade's rules. However, examination of the molecular structures of both species shows that the {RhP₂} planes are inclined by ca. 66° with respect to the metal-bonded SB₃ or CB₃ faces, and that two weak ortho-CHRh agostic interactions occupy the vacant co-ordination position thereby created. As a consequence of these agostic bonds the Rh atom, and hence the overall cluster, is provided with an additional electron pair, meaning that their nido structures are now fully consistent with Wade's rules. The chelated diphosphine compound 8,8-(dppe)-8,7-nido-RhSB₉H₁₀ is similar to the PPh₃ compound in showing the same agostic bonding. Attempts to prepare a bis-P(OMe)₃ analogue result in ligand scavenging and the formation of 8,8,8-{P(OMe)₃}₃-8,7-nido-RhSB₉H₁₀. Similarly, reaction between Cs[6-arachno-SB₉H₁₂] and RhCl(dmpe)CO does not result in CO loss but in formation of 8,8-(dmpe)-8-(CO)-8,7-nido-RhSB₉H₁₀, shown to exist as a mixture of two of three possible rotamers. Deprotonation of 8,8-(PPh₃)₂-8,7-nido-RhSB₉H₁₀ and 8,8-(dppe)-8,7-nido-RhSB₉H₁₀ with MeLi yields the anions [1,1-(PPh₃)₂-1,2-closo-RhSB₉H₉]⁻ and [1,1-dppe-1,2-closo-RhSB₉H₉]⁻, respectively, with octadecahedral cage structures. It is argued that anion formation causes the agostic bonding to be `switched-off' and results in the cluster adopting the closo architecture predicted by Wade's rules. This structural change is fully reversible on reprotonation, and if reprotonation of [1,1-(dppe)-1,2-closo-RhSB₉H₉]⁻ is carried out in MeCN, the product 8,8-(dppe)-8-(MeCN)-8,7-nido-RhSB₉H₁₀ forms. Interestingly, 8,8-(dppe)-8-(MeCN)-8,7-nido-RhSB₉H₁₀ reconverts to 8,8-(dppe)-8,7-nido-RhSB₉H₁₀ on standing in CDCl₃, suggesting that the agostic bonding is sufficiently strong to displace co-ordinated MeCN. All new compounds are fully characterised by multinuclear NMR spectroscopy and, in many cases, by single crystal X-ray diffraction.     

Stability and Structure of Activated Macrocycles. Ligands with Biological Applications

Single p-toluic acid pendant groups were attached to 1,4,7,10,13-pentaazacyclopentadecane (15aneN5) and 1,4,8,11-tetraazacyclotetradecane (cyclam) to prepare bifunctional reagents for radiolabeling monoclonal antibodies with (64,67)Cu. The ligands are 1,4,7,10,13-pentaazacyclopentadecane-1-(alpha-1,4-toluic acid) (PCBA) and 1,4,8,11-tetraazacyclotetradecane-1-(alpha-1,4-toluic acid) (CPTA). For the parent macrocycles and their pendant arm derivatives, the 1:1 Cu(2+) complexes dissociate only below pH 2. At pH 0.0 and 25 degrees C the CPTA-Cu complex has a half-life toward complete dissociation of 24 days. A new approach was developed for the estimation of the Cu(2+) stability constant for the kinetically robust CPTA. All other formation constants were determined at 25.0 degrees C with batch spectrophotometric techniques. Potentiometric titrations were used to determine the protonation constants of the macrocyclic ligands as well as of the metal chelates. The protonation constants, stability constants, and pM's are discussed in terms of both molecular mechanics calculations and the ligands' potential applicability as copper(II) radiopharmaceuticals.     

Short-chain reactive probes as tools to unravel the Pseudomonas aeruginosa quorum sensing regulon

In recent years, the world has seen a troubling increase in antibiotic resistance among bacterial pathogens. In order to provide alternative strategies to combat bacterial infections, it is crucial deepen our understanding into the mechanisms that pathogens use to thrive in complex environments. Most bacteria use sophisticated chemical communication systems to sense their population density and coordinate gene expression in a collective manner, a process that is termed “quorum sensing” (QS). The human pathogen Pseudomonas aeruginosa uses several small molecules to regulate QS, and one of them is N-butyryl-l-homoserine lactone (C₄-HSL). Using an activity-based protein profiling (ABPP) strategy, we designed biomimetic probes with a photoreactive group and a ‘click’ tag as an analytical handle. Using these probes, we have identified previously uncharacterized proteins that are part of the P. aeruginosa QS network, and we uncovered an additional role for this natural autoinducer in the virulence regulon of P. aeruginosa, through its interaction with PhzB1/2 that results in inhibition of pyocyanin production.

Short-chain reactive probes can be used as tools to shed new light on virulence mechanisms in bacterial pathogens.     

Molecular Mechanics Investigation of Gadolinium(III) Complexes

Parameters for the commercially available modeling package SYBYL have been developed for Gd(3+) complexes allowing these to be studied with molecular mechanics. With these parameters and a technique termed the "coordination scan", the coordination numbers of Gd(III) based complexes can be predicted, and thus the hydration number q determined. Knowledge of q has allowed the prediction of molar relaxivities based on correlations to literature values. In addition, the calculated value DeltaE(coord) was found to successfully predict the thermodynamic stability constants for polyamino carboxylate ligands with Gd(3+). Gadolinium complexes are commonly utilized as MRI contrast agents, and thus the techniques utilized in this work should aid in the development of new contrast agents.