Dataset Information

Modeling Pyran Formation in the Molybdenum Cofactor: Protonation of Quinoxalyl-Dithiolene Promoting Pyran Cyclization.

ABSTRACT: Mononuclear Mo and W enzymes require a unique ligand known as molybdopterin (MPT). This ligand binds the metal through a dithiolene chelate, and the dithiolene bridges a reduced pyranopterin group. Pyran scission and formation have been proposed as a reaction of the MPT ligand that may occur within the enzymes to adjust reactivity at the Mo atom. We address this issue by investigating oxo-Mo(IV) model complexes containing dithiolenes substituted by pterin or quinoxaline and a hydroxyalkyl poised to form a pyran ring. While the pterin-dithiolene model complex exhibits a low energy, reversible pyran cyclization, here we report that pyran cyclization does not spontaneously occur in the quinoxalyl-dithiolene model. However, protonating the quinoxalyl-dithiolene model induces pyran cyclization forming an unstable, pyrano-quinoxalyl-dithiolene complex which subsequently dehydrates and rearranges to a pyrrolo-quinoxlyl-dithiolene complex that was previously characterized. The protonated pyrano-quinoxalyl-dithiolene complex was characterized by absorption spectroscopy and cyclic voltammetry, and these results suggest pyran cyclization leads to a significant change in the Mo electronic structure exhibited as a strong intraligand charge transfer (ILCT) transition and 370 mV positive shift of the Mo(V/IV) reduction potential. The influence of protonation on quinoxaline reactivity supports the hypothesis that the local protein environment in the second coordination sphere of molybdenum cofactor (Moco) could control pyran cyclization. The results also demonstrate that the remarkable chemical reactivity of the pterin-dithiolene ligand is subtly distinct and not reproduced by the simpler quinoxaline analog that is often used to replace pterin in synthetic Moco models.

SUBMITTER: Gisewhite DR

PROVIDER: S-EPMC6572731 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Publications

Modeling Pyran Formation in the Molybdenum Cofactor: Protonation of Quinoxalyl-Dithiolene Promoting Pyran Cyclization.

Gisewhite Douglas R DR Nagelski Alexandra L AL Cummins Daniel C DC Yap Glenn P A GPA Burgmayer Sharon J N SJN

Inorganic chemistry 20190403 8

Mononuclear Mo and W enzymes require a unique ligand known as molybdopterin (MPT). This ligand binds the metal through a dithiolene chelate, and the dithiolene bridges a reduced pyranopterin group. Pyran scission and formation have been proposed as a reaction of the MPT ligand that may occur within the enzymes to adjust reactivity at the Mo atom. We address this issue by investigating oxo-Mo(IV) model complexes containing dithiolenes substituted by pterin or quinoxaline and a hydroxyalkyl poised ...[more]

PMID: 30942584

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Project description:The complex [TEA][Tp*MoIV(O)(S2BMOPP)] (1) [TEA = tetraethylammonium, Tp* = tris(3,5-dimethylpyrazolyl)hydroborate, and BMOPP = 6-(3-butynyl-2-methyl-2-ol)-2-pivaloyl pterin] is a structural analogue of the molybdenum cofactor common to all pyranopterin molybdenum enzymes because it possesses a pyranopterin-ene-1,2-dithiolate ligand (S2BMOPP) that exists primarily in the ring-closed pyrano structure as a resonance hybrid of ene-dithiolate and thione-thiolate forms. Compound 1, the protonated [Tp*MoIV(O)(S2BMOPP-H)] (1-H) and one-electron-oxidized [Tp*MoV(O)(S2BMOPP)] [1-Mo(5+)] species have been studied using a combination of electrochemistry, electronic absorption, and electron paramagnetic resonance (EPR) spectroscopy. Additional insight into the nature of these molecules has been derived from electronic structure computations. Differences in dithiolene C-S bond lengths correlate with relative contributions from both ene-dithiolate and thione-thiolate resonance structures. Upon protonation of 1 to form 1-H, large spectroscopic changes are observed with transitions assigned as Mo(xy) → pyranopterin metal-to-ligand charge transfer and dithiolene → pyranopterin intraligand charge transfer, respectively, and this underscores a dramatic change in electronic structure between 1 and 1-H. The changes in electronic structure that occur upon protonation of 1 are also reflected in a large >300 mV increase in the Mo(V/IV) redox potential for 1-H, resulting from the greater thione-thiolate resonance contribution and decreased charge donation that stabilize the Mo(IV) state in 1-H with respect to one-electron oxidation. EPR spin Hamiltonian parameters for one-electron-oxidized 1-Mo(5+) and uncyclized [Tp*MoV(O)(S2BDMPP)] [3-Mo(5+)] [BDMPP = 6-(3-butynyl-2,2-dimethyl)-2-pivaloyl pterin] are very similar to each other and to those of [Tp*MoVO(bdt)] (bdt = 1,2-ene-dithiolate). This indicates that the dithiolate form of the ligand dominates at the Mo(V) level, consistent with the demand for greater S → Mo charge donation and a corresponding increase in Mo-S covalency as the oxidation state of the metal is increased. Protonation of 1 represents a simple reaction that models how the transfer of a proton from neighboring acidic amino acid residues to the Mo cofactor at a nitrogen atom within the pyranopterin dithiolene (PDT) ligand in pyranopterin molybdenum enzymes can impact the electronic structure of the Mo-PDT unit. This work also illustrates how pyran ring-chain tautomerization drives changes in resonance contributions to the dithiolene chelate and may adjust the reduction potential of the Mo ion.

Dataset Information

Modeling Pyran Formation in the Molybdenum Cofactor: Protonation of Quinoxalyl-Dithiolene Promoting Pyran Cyclization.

Publications

Modeling Pyran Formation in the Molybdenum Cofactor: Protonation of Quinoxalyl-Dithiolene Promoting Pyran Cyclization.

Similar Datasets

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