Reduction of Quinones by NADH Catalyzed by Organoiridium Complexes

Liu, Zhe; Deeth, Robert J.; Butler, Jennifer S.; Habtemariam, Abraha; Newton, Mark E.; Sadler, Peter J.

doi:10.1002/ange.201300747

Cited by 32 publications

(21 citation statements)

References 48 publications

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“…Ther eduction of quinones has been investigated by chemical, photochemical, and enzymatic methods because of its biological and industrial significance. [18] In these processes,m etal complexes or coenzyme NADH were used as electron donors.H owever, our experimental and theoretical investigations suggested that the boryl radical intermediate (INT4)may act as anovel electron donor for the reduction of quinones (see Scheme S5). Therefore,the present Lewis base/B 2 (pin) 2 system provides an ew strategy for the reduction of quinones.…”

Section: Methodsmentioning

confidence: 99%

Homolytic Cleavage of a B−B Bond by the Cooperative Catalysis of Two Lewis Bases: Computational Design and Experimental Verification

et al. 2016

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Density functional theory (DFT) investigations revealed that 4-cyanopyridine was capable of homolytically cleaving the BÀB s bond of diborane via the cooperative coordination to the two boron atoms of the diborane to generate pyridine boryl radicals.Our experimental verification provides supportive evidence for this new B À Ba ctivation mode.Witht his novel activation strategy,wehave experimentally realized the catalytic reduction of azo-compounds to hydrazine derivatives,d eoxygenation of sulfoxides to sulfides, and reduction of quinones with B 2 (pin) 2 at mild conditions. Diborane compounds,R 2 B À BR 2 ,a re highly useful synthetic modules for concise synthesis of organoboronates, [1] which are versatile building blocks for the generation of new chemical bonds using the Suzuki-Miyaura crossing-coupling reactions. [2] Many transition-metal complexes are known to be able to effectively cleave the B À Bb ond of diborane and catalyze the borylation or diboration of unsaturated organic substrates. [3,4] On the other hand, transitionmetal-free catalytic systems for activating the BÀB bond of diborane compounds have also attracted much attention. [5] Recently,t he Lewis adducts of sp 2 -sp 3 diborane compounds have been reported for the borylation or diboration of unsaturated substrates. [5][6][7][8][9] It has been shown that diborane compounds became asource of nucleophilic boryl moiety,w hen one of the boron atoms of the diborane was tetracoordinated to as trong base (Scheme 1a). In such cases,t he B-(sp 2 ) À B(sp 3 )b onds are always cleaved heterolytically. [6c, 7b] In addition, reductive addition of diboranes to sterically hindered pyrazines in the presence of bipyridine derivatives has also been reported. [10] Nevertheless,t he mechanistic details of this reaction are unclear yet. Owing to the high BÀBbond dissociation energy (BDE) of diborane derivatives, [11] strong bases such as N-heterocyclic carbenes (NHC), [6] Cs 2 CO 3 , t-BuOK [7b] are usually used in the activation of diborane compounds.Given the considerable utility of diboranes in synthetic chemistry,i ti sh ighly desirable to develop new strategies for the activation of B À Bb ond.Note that in the Lewis adducts of sp 2 -sp 3 diborane compounds,t here is another sp 2 hybridized boron atom. We envisioned that if the empty porbital of the uncoordinated boron atom is associated with as econd Lewis base,t he BÀB bond would be further weakened, and might be cleaved in ahomolytic manner.With appropriate Lewis bases,the boryl radical generated from the homolytic cleavage of diborane BÀBb ond could be sufficiently stable,t hrough the possible captodative effect. [12] Pyridines with electron-withdrawing substituents may act as appropriate Lewis bases to activate the B À Bbond of diborane compounds as aresult of their high boryl radical stabilization energies (see Scheme S1 in the Supporting Information). Herein, we report ac omputationally designed and experimentally verified catalyst which can homolytically cleave the BÀBb ond of B 2 (pin) 2 via the coo...

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Section: Methodsmentioning

confidence: 99%

Homolytic Cleavage of a B−B Bond by the Cooperative Catalysis of Two Lewis Bases: Computational Design and Experimental Verification

et al. 2016

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“…44,45 Our recent work demonstrates that potent Ir anticancer complexes such as 3 and 12 can accept hydride from NADH in aqueous solution ( 1 H NMR Ir–H −14.7 ppm). The hydride can further be transferred to oxygen to generate H 2 O 2 , Figure 16b.…”

Section: Organometallic Iridium Anticancer Agentsmentioning

confidence: 99%

“…(d) Proposed mechanism for the catalytic reduction of duroquinone by NADH/Ir system. Adapted from ref (45). …”

Section: Organometallic Iriii Complexes As Biocatalystsmentioning

confidence: 99%

Organoiridium Complexes: Anticancer Agents and Catalysts

2014

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ConspectusIridium is a relatively rare precious heavy metal, only slightly less dense than osmium. Researchers have long recognized the catalytic properties of square-planar IrI complexes, such as Crabtree’s hydrogenation catalyst, an organometallic complex with cyclooctadiene, phosphane, and pyridine ligands. More recently, chemists have developed half-sandwich pseudo-octahedral pentamethylcyclopentadienyl IrIII complexes containing diamine ligands that efficiently catalyze transfer hydrogenation reactions of ketones and aldehydes in water using H2 or formate as the hydrogen source. Although sometimes assumed to be chemically inert, the reactivity of low-spin 5d6 IrIII centers is highly dependent on the set of ligands. Cp* complexes with strong σ-donor C∧C-chelating ligands can even stabilize IrIV and catalyze the oxidation of water. In comparison with well developed Ir catalysts, Ir-based pharmaceuticals are still in their infancy. In this Account, we review recent developments in organoiridium complexes as both catalysts and anticancer agents.Initial studies of anticancer activity with organoiridium complexes focused on square-planar IrI complexes because of their structural and electronic similarity to PtII anticancer complexes such as cisplatin. Recently, researchers have studied half-sandwich IrIII anticancer complexes. These complexes with the formula [(Cpx)Ir(L∧L′)Z]0/n+ (with Cp* or extended Cp* and L∧L′ = chelated C∧N or N∧N ligands) have a much greater potency (nanomolar) toward a range of cancer cells (especially leukemia, colon cancer, breast cancer, prostate cancer, and melanoma) than cisplatin. Their mechanism of action may involve both an attack on DNA and a perturbation of the redox status of cells. Some of these complexes can form IrIII-hydride complexes using coenzyme NAD(P)H as a source of hydride to catalyze the generation of H2 or the reduction of quinones to semiquinones. Intriguingly, relatively unreactive organoiridium complexes containing an imine as a monodentate ligand have prooxidant activity, which appears to involve catalytic hydride transfer to oxygen and the generation of hydrogen peroxide in cells. In addition, researchers have designed inert IrIII complexes as potent kinase inhibitors. Octahedral cyclometalated IrIII complexes not only serve as cell imaging agents, but can also inhibit tumor necrosis factor α, promote DNA oxidation, generate singlet oxygen when photoactivated, and exhibit good anticancer activity. Although relatively unexplored, organoiridium chemistry offers unique features that researchers can exploit to generate novel diagnostic agents and drugs with new mechanisms of action.

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“…6). The complex [Cp*Ir(phen)Cl]PF 6 was employed to catalyze the reduction of quinones in a biomimetic reaction of ubiquinone oxidoreductase [37]. Sadler analyzed the influence of the nature of the arene cap and the N,N-bidentate ligand for Noyori type ruthenium complexes.…”

Section: Pioneering Non-enzymatic Approaches For the Regeneration Of mentioning

confidence: 99%