Half-sandwich rhodium(III) transfer hydrogenation catalysts : reduction of NAD+ and pyruvate, and antiproliferative activity

Article English OPEN
Soldevila-Barreda, Joan J. ; Habtemariam, Abraha ; Romero-Canelón, Isolda ; Sadler, P, J. (2015)

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.\ud
  • References (56)
    56 references, page 1 of 6

    [1] S. Ogo, T. Matsumoto, A. Robertson, The development of aqueous transfer hydrogenation catalysts, Dalton Trans. 40 (2011) 10304-10310.

    [2] X. Wu, C. Wang, J. Xiao, Asymmetric transfer hydrogenation in water with platinum group metal catalysts, Platin. Met. Rev. 54 (2010) 3-19.

    [3] S. Gladiali, E. Alberico, Asymmetric transfer hydrogenation: chiral ligands and applications, Chem. Soc. Rev. 35 (2006) 226-236.

    [4] P. Brandt, P.G. Andersson, J. Backvall, J.S.M. Samec, Mechanistic aspects of transition metal-catalyzed hydrogen transfer reactions, Chem. Soc. Rev. 35 (2006) 237-248.

    [5] T.R. Ward, Artificial metalloenzymes based on the biotin-avidin technology: enantioselective catalysis and beyond, Acc. Chem. Res. 44 (2011) 47-57.

    [6] J. Wu, F. Wang, Y. Ma, X. Cui, L. Cun, J. Zhu, J. Deng, B. Yu, Asymmetric transfer hydrogenation of imines and iminiums catalyzed by a water-soluble catalyst in water, Chem. Commun. 1766-1768 (2006).

    [7] D.S. Matharu, D.J. Morris, G.J. Clarkson, M. Wills, An outstanding catalyst for asymmetric transfer hydrogenation in aqueous solution and formic acid/triethylamine, Chem. Commun. (2006) 3232-3234.

    [8] T. Völker, E. Meggers, Transition-metal-mediated uncaging in living human cells-an emerging alternative to photolabile protecting groups, Curr. Opin. Chem. Biol. 25 (2015) 48-54.

    [9] J.J. Soldevila-Barreda, P.J. Sadler, Approaches to the design of catalytic metallodrugs, Curr. Opin. Chem. Biol. 25 (2015) 172-183.

    [10] P.K. Sasmal, C.N. Streu, E. Meggers, Metal complex catalysis in living biological systems, Chem. Commun. 49 (2013) 1581-1587.

  • Related Research Results (1)
  • Metrics
    No metrics available
Share - Bookmark