TIFR
Department of Chemical Sciences
School of Natural Sciences

November 8, 2017 at 2.30 pm in AG-80

Title :

Chemical Detoxification of Neurotoxic Methylmercury by Smart Molecules

Abstract :

Methylmercury (MeHg+) is considered to be the most toxic form of mercury due to its ability to accumulate in fat tissues leading to its bio-magnification within the food chain. The toxicological implications associated with the ingestion of MeHg+ may also differ according to its chemical form.1 All seafood, mainly fish, contains mercury, primarily in the form of methylmercury. Consumption of mercury contaminated fish on a regular basis therefore could cause adverse neurodevelopmental, cardiovascular, and immunological health effects. High levels of mercury in fish stocks have been found in mining (Singrauli region in MP and Sonbhadra district in UP), and coastal areas, particularly Ulhas River Estuary and Thane Creek areas, Mumbai (mercury levels in fish from these contaminated areas: 0.89-1.78 mg total Hg/kg dry weight (dw); crabs had 1.42-4.94 mg total Hg/kg dw mercury compared to the permissible limit of 0.5 mg/kg).

 

In nature, however, several microorganisms have been reported as being MeHg+ tolerant due to their ability to convert highly toxic MeHg+ to either less toxic volatile elemental mercury, Hg0 or biologically inert insoluble HgS (metacinnabar). For instance, bacterial organomercurial lyase (MerB) catalyzes the protolytic cleavage of the otherwise inert Hg-C bond of MeHg+ and produces methane (CH4) gas and ionic mercury Hg2+, while a second enzyme mercuric ion reductase (MerA) reduces the product Hg2+ to volatile Hg0. On the other hand, several sulfate reducing bacteria (SRB) convert highly toxic MeHg+ to less toxic insoluble HgS(s) by producing H2S during metabolism.3 In addition, insoluble mercury selenide (HgSe) particles have also been found in a wide range of tissues of marine mammals (whales and dolphins) and also detected in various organs (kidney, liver, muscle, and brain) of humans exposed to MeHg+. HgSe is considered to be much less toxic than mobile, soluble MeHg+ species including MeHgCys and MeHgSG. In this talk I will mainly focus on how small organic molecules can be used intelligently to detoxify highly neurotoxic methylmercury by two distinct pathways, similar to those observed in nature.4-8

 

References:

 

  1. Harris, H. H. et al. Science 2003, 301, 1203; Stern, A. H. et al. Science 2004, 303, 763–766; Korbas, M. et al. ACS Chem. Biol. 2012, 7, 411–420.
  2. Menon, J. S. Indian J. Mar. Sci. 2013, 42, 812; Report of Centre for Science and Environment (CSE), 2012; Deshpande. A et al. Environ Monit assess 2009, 159, 493.
  3. Baldi, F et al. Appl. Environ. Microbiol. 1993, 59, 2479; Clarkson, T. W. et al. Crit. Rev. Toxicol. 2006, 36, 609; Benison, G. C. et al. Biochemistry 2004, 43, 8333; Hong, B. et al. Biochemistry 2010, 49, 8187; Omichinski, J. G. et al. J. Biol. Chem. 2009, 284, 938;
  4. Roy, G. et al. Angew. Chem., 2015, 127, 9455; Angew. Chem. Int. Ed., 2015, 54, 9323. This work is highlighted in Cover Page; Angew. Chem., 2015, 127, 9551; Angew. Chem. Int. Ed., 2015, 54, 9419.
  5. Roy, G. et al. Chem. Eur. J, 2017, 23 (24), 5696. This article is highlighted in "Frontispiece" and considered as "Hot Paper"
  6. International Patent filed (PCT): WO2017168451. 
  7. Roy, G. et al. Inorg. Chem. 2017, xx, xxxx (DOI: 10.1021/acs.inorgchem.7b01301). 
  8. Roy, G. et al. Inorg. Chem. 2017, xx, xxxx (DOI: 10.1021/acs.inorgchem.7b01048).