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High nuclearity carbonyl clusters of ruthenium and osmium are found to exhibit good photoacoustic (PA) activity in the near-IR (NIR) region. Their potential as PA contrast agents for full body imaging has been demonstrated for the first time with mice; intravenous administration of the osmium carbonyl cluster Na-2[Os-10(mu(6)-C)(CO)(24)] afforded up to a four-fold enhancement of the PA signal in various tissues. The cluster exhibits low toxicity, high stability and superior PA stability compared to the clinically approved NIR dye, indocyanine green.

The ruthenacyclic carbamoyl complexes [RuBr(2-NHC(O)C5H3N-4-R)(CO)2(MeCN)] in which the 4-position of the pyridinyl ring is derivatized, have been synthesized. These are ruthenium-based structural mimics of the natural [Fe]-hydrogenase metal cofactor. The derivative with R = H reacts with phosphine to form a disubstituted product [RuBr(2-NHC(O)C5H4N)(CO)(PPh2SPh)2].

Metal carbonyls, a class of organometallic complexes that consist of carbon monoxide (CO) ligands coordinated to a metal center, show intense CO vibrational frequencies in the mid-infrared (IR) 2200-1800 cm-1. This region is unique to the metal carbonyl species and is typically free of interference by other biomolecules. This property can be put to good use for mid-IR bio-sensing, which was first demonstrated by Jaouen and co-workers in the development of IR-based quantitative assays for detecting various biomolecules. In this thesis, the concept is extended to surface-enhanced Raman spectroscopy (SERS) through the development of metal carbonyl-based Raman reporters. The conjugation of two classes of metal carbonyls, namely, metal carbonyl clusters and mononuclear half-sandwich metal carbonyl complexes, onto colloidal gold nanospheres gave good CO vibrational stretches in the 1800-2200 cm-1 region. Alterations to the ligand sphere and the charge (for cluster complexes) were found to be effective in tuning the CO vibrational stretches over a wide frequency range. It was also observed that the SERS enhancement was highly dependent on the extent of aggregation of the colloid. In another extension, a SERS-active planar substrate was utilized in tandem with a triosmium carbonyl cluster-boronic acid conjugate acting as a secondary saccharide probe, in a sensitive and selective SERS-based glucose assay. While investigating extension of this idea to the detection of cancer cells via their surface glycans, thiolato triosmium carbonyl clusters of the type Os3(u-H)(u-SAryl)(CO)10 were found to be cytotoxic. Cell death was found to be via the induction of apoptosis. Metal carbonyl clusters were also demonstrated to be good contrast agents for photoacoustic (PA) imaging. The cluster nuclearity was shown to be a useful parameter for fine-tuning the absorption wavelength, as increasing the cluster nuclearity shifted the absorption into the near-IR region. The high nuclearity carbonyl cluster [Os10(u6-C)(CO)24]2- was shown to exhibit good PA properties in the NIR region, and its sodium salt was applied successfully for the whole body PA imaging of live mice. ​Doctor of Philosophy (SPMS)

Transition metal carbonyls exhibit strong CO absorptions in the 2200–1800 cm−1 region, which is free of interference from other functional groups. This feature has led to their applications in bio-imaging and -sensing, in particular through mid-IR, Raman and more recently, surface-enhanced Raman spectroscopy (SERS). Their use in mid-IR quantitative sensing based on vibrational intensities, and chemical sensing based on frequency shifts and vibrational lifetimes, is reviewed. Their development for Raman sensing following the breakthrough in SERS highlights the potential of coupling metal carbonyls to plasmonic nanostructures as novel optical materials for SERS-based bio-imaging and -sensing. ASTAR (Agency for Sci., Tech. and Research, S’pore) Accepted version

We report, for the first time, the use of a water-soluble organometallic compound as a stable, reliable and high-contrast photoacoustic contrast agent. This gives a significantly higher contrast than that achievable with alternatives such as single-walled carbon nanotubes. Image enhancement of the rat cerebral cortex vasculature was observed using in vivo dark-field photoacoustic microscopy. ASTAR (Agency for Sci., Tech. and Research, S’pore) Accepted version

A metal carbonyl-functionalized nanostructured substrate can be used in a rapid and simple assay for the detection of A1AT, a potential biomarker for bladder cancer, in clinical urine samples. The assay involves monitoring changes in the carbonyl stretching vibrations of the metal carbonyl via surface-enhanced Raman spectroscopy (SERS). These vibrations lie in the absorption spectral window of 1800–2200 cm−1, which is free of any spectral interference from biomolecules. ASTAR (Agency for Sci., Tech. and Research, S’pore) ASTAR (Agency for Sci., Tech. and Research, S’pore)

Conjugates of organometallic osmium carbonyl clusters and gold nanoparticles show a strong carbonyl signal in surface-enhanced Raman spectroscopy. The ease of bio-functionalization and the high stability and good dispersibility in aqueous solution make these conjugates excellent candidates for biomedical applications, as demonstrated by live-cell imaging with the carbonyl signals of OM-NP(PEG)-L conjugates.