Inspired by Nature-Functional Analogues of Molybdenum and Tungsten-Dependent Oxidoreductases

Abstract

Throughout the previous ten years many scientists took inspiration from natural molybdenum and tungsten-dependent oxidoreductases to build functional active site analogues. These studies not only led to an ever more detailed mechanistic understanding of the biological template, but also paved the way to atypical selectivity and activity, such as catalytic hydrogen evolution. This review is aimed at representing the last decade's progress in the research of and with molybdenum and tungsten functional model compounds. The portrayed systems, organized according to their ability to facilitate typical and artificial enzyme reactions, comprise complexes with non-innocent dithiolene ligands, resembling molybdopterin, as well as entirely non-natural nitrogen, oxygen, and/or sulfur bearing chelating donor ligands. All model compounds receive individual attention, highlighting the specific novelty that each provides for our understanding of the enzymatic mechanisms, such as oxygen atom transfer and proton-coupled electron transfer, or that each presents for exploiting new and useful catalytic capability. Overall, a shift in the application of these model compounds towards uncommon reactions is noted, the latter are comprehensively discussed.

Keywords: OAT; acetylene hydratase; dithiolene; functional models; hydrogen evolution; oxidoreductases.

Figure 1

Potential redox activity (and intramolecular electron transfer) of the dithiolene ligand system constituting the foundation of its non-innocent nature.

Figure 2

Classification of mononuclear molybdenum and tungsten-dependent oxidoreductases enzymes into families according to Hille (all shown as fully oxidized metals) and the chemical structure of molybdopterin: (a) DMSO reductase family (b) sulfite-oxidase family (c) xanthine oxidase family (d) formate dehydrogenase family (e) aldehyde ferredoxin oxidoreductase family (f) acetylene dehydratase (g) molybdopterin (MPT, reduced form) [5,6,7].

Figure 3

Catalytic cycle of sulfite oxidase with its two half reactions: the OAT (right) and the PCET (left).

Figure 4

Selected dithiolene ligands used for the catalytic and the non-catalytic examination of oxygen atom transfer (OAT) reactivity.

Figure 5

Mechanism of E atom transfer reactions (E = chalcogenide atom) from metal centers to organophosphines (PR₃). The formal oxidation state of the metal changes from +VI to +IV; phosphorous is concomitantly oxidized. k₁, k₋₁, and k₂ represent the respective reaction rates. The figure was adapted from the original literature [38,46].

Figure 6

Comparison of the hydrogen bonding interactions in the molybdopterin moiety (a), with the different substituted aromatic ligand systems 1,2-S₂-3-R-CONHC₆H₃ (2N-bdt, (b)), 1,2-S₂-3-R-CONHC₆H₃ (N-bdt, (c)) and 1,2-S₂-3-^tBu-NHCOC₆H₃ (O-bdt, (d)) introduced by the groups of Ueyama and of Onitsuka [51,52,60].

Figure 7

Proposed mechanism for the artificial PCET reaction with Mo^IVOL₂ (L = bdt, dmed). The reaction cascade starts with an electrochemical activation (top) followed by a consumption of two hydroxide ions to produce a Mo^VO₂L₂ complex which can disproportionate, resulting in a Mo^VIO₂L₂ species (bottom). The figure was adapted from [48].

Figure 8

(a–c) Employed ligand systems for FDH functional analogues based on a fused quinoxaline-pyrane ring system with oxidized (qpdt, (a)), semi-reduced (H-qpdt, (b)) and fully-reduced (2H-qpdt, (c)) pyrazine/piperazine ring, respectively (* represents chirality), (d,e) comparison of the active site of MoCu CO dehydrogenase 2 (MPT only shown as dithiolene) (d) with the synthetic analogue (Et₄N)₂[(bdt)Mo^VIO(µ-S)₂Cu^ICN] (e) introduced by Fontecave et al. [76,78,84].

Figure 9

Proposed catalytic cycle for CO₂ activation yielding formate and H₂ by the novel (Et₄N)₂[(bdt)Mo^VIO(µ-S)₂Cu^ICN] complex, a functional analogue of the Mo/Cu CO dehydrogenase 2. The standard potential in the second step is given vs. Fc⁺/Fc and constitutes a one-electron reduction into the ligand-based molecular orbital with almost exclusively S_3p-character; TFE = Trifluorethanol. Adapted from the original report [84].

Figure 10

Scorpionate ligands bis(3,5-dimethyl-4-vinylpyrazol-1-yl)acetic acid (bpa, (a)) and bis(3,5-dimethyl-4-vinylpyrazol-1-yl)methane (bpm, (b)) used for homogenous and heterogenous OAT catalysis. The vinyl groups are connected to acrylate linkers resulting in a polymer [105]. Heteroscorpionate ligands based on Tp* with a thiolate (L3S, (c)) or an alcoholate (L10O, (d)) replacing one pyrazolyl moiety [19].

Figure 11

Selected non-dithiolene ligand systems used for OAT catalysis: (a) 2,2′-chalcogenobis(4,6-di-tertbutylphenol) (Cbbp) [20], (b) 1,4-diazepane-based mono(phenolate) [21], (c) 2-(2′-hydroxyphenyl)-2-oxazoline (hoz) [25,109], (d) pyrimidine- (PymS) and pyridine-2-thiolate (PyS) [15,108], (e) 1,2-dithiaalkanediyl-2,2′-bisphenolate (OSSO) [23], (f) 1,4-diazepane-based bis(phenolate) [22], (g) ethylenediamine-based-bis(phenolate) [22].

Figure 12

Comparison of the first shell (left) and second shell mechanism (middle) regarding the binding mode of the substrate to the active site of acetylene hydratase. MPT (right) is shown as pruned on the left. Adapted from the literature [147].

Figure 13

Reactivity of model complexes [M^II(CO)(C₂H₂)(6-MePyS)₂] (M=Mo, W; 6-MePyS = 6-methylpyridine-2-thiolate) exhibiting acetylene activation; (i) CH₂Cl₂, under C₂H₂ atmosphere, 24 h; (ii) 3 eq. PMe₃, CH₂Cl₂, 4 h; (iii) M = Mo, 1.15 eq. Me₃NO, CH₂Cl₂, 0 °C, 1.5 h; M = W, 1.15 eq. pyridine-N-oxide, CH₂Cl₂, 20 h; (iv) M = Mo, 3 eq. PMe₃, CH₂Cl₂, 1.5 h; M = W, 3 eq. PMe₃, CH₂Cl₂, 7 h; (v) 5 eq. H₂O, 5 eq. Et₃N, CH₃CN, 15 h [151,152,153].

Figure 14

Proposed catalytic mechanism for the hydrogen evolution reaction mediated by a [M^VIO₂(dt)₂]²⁻ (1); M = W, Mo; dt = dithiolene) or [M^IVO(dt)₂]²⁻ (2) complex catalyst. 1 represents the pre-catalyst which is converted into the active catalyst 2. I and II are non-isolable intermediates during the catalytic cycle yielding the transition state II-TS which releases hydrogen when transforming back to 1. Adapted from the original literature reports [78,170].

Figure 15

Selected non-natural reaction products associated with functional analogues of molybdenum and tungsten-dependent oxidoreductases (a–d). (a) [Mo(CO)₂(CH₂-dt)(dppe)] (dt: cydt = cyclohex-1-ene-1,2-dithiolate or tpydt = 5,6-dihydro-2H-thiopyran-3,4-dithiolate; dppe = 1,2-bis(diphenylphosphino)ethane) [36], (b) [Mo(tfd)₂(SC₆H₄SPPh₃)(PPh₃)] [176], (c) [M(C₂H₄)₂(CO₂)(PNP)] (M = Mo, W; PNP = 2,6-bis(diphenylphosphinomethyl)pyridine) [177], (d) [M(C₂H₄)(CO)₂(PNP)] [177] (e,f) Two possible binding modes of ethylene to [Ni(tfd)₂] (tfd = 1,2-trifluoromethyl-1,2-dithiolate) [169,175,178].