Carlos Romão Lab

	The Laboratory of Organometallic Chemistry is presently studying new metal carbonyl complexes to be used as Carbon Monoxide Releasing Molecules (CORM) a new class of drugs based on the therapeutic activity of CO.
	Carlos C. Romão Professor Catedrático, retired PhD in 1998, Instituto Superior Técnico, Portugal Phone (+351) 214469751 Extension 1751 ccr@itqb.unl.pt

Research Interests

Carbon monoxide (CO) is an odorless, colorless, toxic gas at atmospheric pressure which is usually generated upon incomplete combustion of organic matter or fuels. Electronically similar to N₂, it is rather inert. However, in contrast to N₂, CO binds transition metals forming metal carbonyls (MC). The chemistry of MCs has been intensively explored since it allows CO to be used as an industrial source of organic molecules like synthetic gasoline and aldehydes. Some metals and even bacteria also catalyze the reaction of CO with water to produce hydrogen.

The perplexing observation (1949) that CO is produced in our body as the result of normal metabolic and catabolic functions led to the discovery that CO is involved in multiple cellular defense mechanisms in physiologic and pathologic situations, e.g. as a strong anti-inflammatory, anti-apoptotic, vasodilation and bactericidal agent. Inhalation of CO gas produces significant therapeutic effects in many animal models of disease and is being tested in several human clinical trials. However, the toxicity of inhaled CO gas at high concentrations, as needed for therapy, poses safety limitations to its therapeutic application. This problem can be circumvented by the use of molecules that are able to deliver CO to the diseased tissues in a controlled manner. In this way, the amount of CO needed for the therapeutic action is very small avoiding general CO toxicity. Such molecules are called CO Releasing Molecules (CORM). Mimicking Nature, that uses metal complexes like hemes to transport CO, the group became an early developer of metal based CORMs, namely through its spin-off start-up, Alfama Inc, recently merged with Proterris Inc. Over a decade of research led the group to establish the methodology for building drug-like organometallic CORMs behaving in vivo as therapeutically effective prodrugs for several clinical indications. Presently, the main research goals are the discovery of new biocidals and of new neuroprotective CORMs.

Group Members

• Joana Teixeira Marques Post-Doc   (50% with Ligia M Saraiva Lab)

Selected Publications

1. Nobre LS, Jeremias H, Romão CC, Saraiva LM. 2016. Examining the antimicrobial activity and toxicity to animal cells of different types of CO-releasing molecules. Dalton Trans. 45(4):1455-1466.

2. Spontaneous CO Release from RuII(CO)2–Protein Complexes in Aqueous Solution, Cells, and Mice.-Protein Complexes Spontaneously Release CO in Aqueous Solution, Live Cells and Mice. Chaves-Ferreira M, Albuquerque IS, Matak-Vinkovic D, Coelho AC, S. M. Carvalho, Saraiva LM, Romão CC and Bernardes GJL Angew. Chem. Int. Ed., 2015, 54, 1172 –1175

3. Romão CC, Blättler WA, Seixas JD and Bernardes GJL 2012. Developing drug molecules for therapy with carbon monoxide. Chem. Soc. Rev. 41, 3571-3583 (highly cited paper)

Laboratory's Website

For further information please visit the laboratory's website

Química Organometálica (PT)

Em aparente contraste com o seu estatuto público de “assassino silencioso” o  monóxido de carbono (CO) é produzido por quase todos os organismos vivos e utilizado por eles em vários mecanismos de defesa celular contra uma grande variedade de agentes de stress. Em consequência dessa defesa, o CO tem efeitos terapêuticos numa larga gama de doenças. Testes em animais, conduzidos com inalação controlada de CO gasoso, confirmaram o seu papel curativo em enfermidades como o enfarte de miocárdio, transplantes, esclerose múltipla e outras. Testes clínicos em humanos estão em curso. No entanto, os riscos associados à inalação de CO limitam o seu uso terapêutico. Essa limitação pode ser evitada usando fármacos capazes de libertar pequenas quantidades de CO apenas nos órgãos afectados tornando a dose de CO libertada no organismo muito inferior à dose tóxica e, portanto, segura. Este tipo de compostos chamados moléculas libertadoras de CO (CORM em inglês) têm sido desenvolvidos por este grupo, através da start-up Alfama Inc recentemente integrada na Proterris Inc, que tem uma posição de liderança mundial neste domínio. Os alvos da actual investigação no grupo são a descoberta de novos CORMs antibióticos e novos agentes de protecção neurológica.

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