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Half-sandwich rhodium(III) transfer hydrogenation catalysts : reduction of NAD+ and pyruvate, and antiproliferative activity
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Soldevila-Barreda, Joan J., Habtemariam, Abraha, Romero-Canelón, Isolda and Sadler, P, J. (2015) Half-sandwich rhodium(III) transfer hydrogenation catalysts : reduction of NAD+ and pyruvate, and antiproliferative activity. Journal of Inorganic Biochemistry, 153 . pp. 322-333. doi:10.1016/j.jinorgbio.2015.10.008 ISSN 0162-0134.
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Official URL: http://dx.doi.org/10.1016/j.jinorgbio.2015.10.008
Abstract
Organometallic complexes have the potential to behave as catalytic drugs. We investigate here Rh(III) complexes of general formula [(Cpx)Rh(N,N′)(Cl)], where N,N′ is ethylenediamine (en), 2,2′-bipyridine (bpy), 1,10-phenanthroline (phen) or N-(2-aminoethyl)-4-(trifluoromethyl)benzenesulfonamide (TfEn), and Cpx is pentamethylcyclopentadienyl (Cp*), 1-phenyl-2,3,4,5-tetramethylcyclopentadienyl (CpxPh) or 1-biphenyl-2,3,4,5-tetramethyl cyclopentadienyl (CpxPhPh). These complexes can reduce NAD+ to NADH using formate as a hydride source under biologically-relevant conditions. The catalytic activity decreased in the order of N,N-chelated ligand bpy > phen > en with Cp* as the η5-donor. The en complexes (1–3) became more active with extension to the CpX ring, whereas the activity of the phen (7–9) and bpy (4–6) compounds decreased. [Cp*Rh(bpy)Cl]+ (4) showed the highest catalytic activity, with a TOF of 37.4 ± 2 h− 1. Fast hydrolysis of the chlorido complexes 1–10 was observed by 1H NMR (< 10 min at 310 K). The pKa* values for the aqua adducts were determined to be ca. 8–10. Complexes 1–9 also catalysed the reduction of pyruvate to lactate using formate as the hydride donor. The efficiency of the transfer hydrogenation reactions was highly dependent on the nature of the chelating ligand and the Cpx ring. Competition reactions between NAD+ and pyruvate for reduction by formate catalysed by 4 showed a preference for reduction of NAD+. The antiproliferative activity of complex 3 towards A2780 human ovarian cancer cells increased by up to 50% when administered in combination with non-toxic doses of formate, suggesting that transfer hydrogenation can induce reductive stress in cancer cells.
Item Type: | Journal Article | ||||||||||
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Subjects: | Q Science > QD Chemistry Q Science > QH Natural history > QH301 Biology R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) |
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry | ||||||||||
Library of Congress Subject Headings (LCSH): | NAD (Coenzyme) , Pyruvates, Antineoplastic agents, Organorhodium compounds | ||||||||||
Journal or Publication Title: | Journal of Inorganic Biochemistry | ||||||||||
Publisher: | Elsevier Science Inc | ||||||||||
ISSN: | 0162-0134 | ||||||||||
Official Date: | December 2015 | ||||||||||
Dates: |
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Volume: | 153 | ||||||||||
Page Range: | pp. 322-333 | ||||||||||
DOI: | 10.1016/j.jinorgbio.2015.10.008 | ||||||||||
Status: | Peer Reviewed | ||||||||||
Publication Status: | Published | ||||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||||
Date of first compliant deposit: | 13 January 2016 | ||||||||||
Date of first compliant Open Access: | 12 February 2016 | ||||||||||
Funder: | European Research Council (ERC), Engineering and Physical Sciences Research Council (EPSRC) | ||||||||||
Grant number: | 247450 ERC, EP/F042159/1 EPSRC |
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