The molybdenum cofactor is composed of a molybdenum coordinated by one or two rather complicated ligands known as either molybdopterin or pyranopterin. Pterin is one of a large family of bicyclic N-heterocycles called pteridines. Such molecules are widely found in Nature, having various forms to perform a variety of biological functions. This article describes the basic nomenclature of pterin, their biological roles, structure, chemical synthesis and redox reactivity. In addition, the biosynthesis of pterins and current models of the molybdenum cofactor are discussed.

The syntheses and X-ray structures of two molybdenum pyranopterin dithiolene complexes in biologically relevant Mo(+4) and Mo(+5) states are reported. Crystallography reveals these complexes possess a pyran ring formed through a spontaneous cyclization reaction of a dithiolene side-chain hydroxyl group at a C=N bond of the pterin. NMR data on the Mo(+4) complex suggests a reversible pyran ring cyclization occurs in solution. These results provide experimental evidence that the pyranopterin dithiolene ligand in molybdenum and tungsten enzymes could participate in catalysis through dynamic processes modulated by the protein.

A model system for the molybdenum cofactor has been developed that illustrates the non-innocent behavior of a N-heterocycle appended to a dithiolene chelate on molybdenum. The pyranopterin of the molybdenum cofactor is modeled by a quinoxalyl-dithiolene ligand (S2BMOQO) formed from reaction of a molybdenum tetrasulfide and a quinoxalyl alkyne. The resulting complexes TEA[Tp*MoX(S2BMOQO)] (1, X = S; 3, X = O; TEA = tetraethylammonium; Tp* = hydrotris(3,5-dimethylpyrazolyl)borate) undergo a dehydration-driven intramolecular cyclization within the quinoxalyl-dithiolene forming Tp*MoX(pyrrolo-S2BMOQO) (2, X= S; 4, X= O). 4 can be oxidized by one electron to produce the Mo(5+) complex 5. In a preliminary report of this work evidence from X-ray crystallography, electronic absorption and resonance Raman spectroscopies, and DFT bonding calculations revealed that 4 possesses an unusual asymmetric dithiolene chelate with significant thione-thiolate character. The results described here provide a detailed description of the reaction conditions that lead to formation of 4. Data from cyclic voltammetry, additional DFT calculations and several spectroscopic methods (infrared, electronic, resonance Raman, electron paramagnetic resonance) have been used to characterize the properties of members in this suite of five Mo(S2BMOQO) complexes and further substantiate the highly electron-withdrawing character of the pyrrolo-S2BMOQO ligand in 2 and 4. This study of the unique non-innocent ligand S2BMOQO provides examples of the roles that the N-heterocycle pterin can play as an essential part of the molybdenum cofactor. The versatile nature of dithiolene appended by heterocycles may aid in modulating the redox processes of the molybdenum center during the course of enzyme catalysis.

A new monoanionic dithiolene ligand is found in Tp*MoO(S2BMOQO). A combination of x-ray crystallography, electronic absorption and resonance Raman spectroscopies, and bonding calculations reveal that the monoanionic dithiolene ligand possesses considerable thiolate-thione character resulting from admixture of an intraligand charge transfer excited state into the ground state wavefunction. The unusual dithiolene exhibits a highly versatile donor-acceptor character that dramatically lowers the Mo(IV/V) redox couple and points to a potentially non-innocent role of the pterin fragment in pyranopterin Mo enzymes.

The preparation and characterization of new model complexes for the molybdenum cofactor are reported. The new models are distinctive for the inclusion of pterin-substituted dithiolene chelates and have the formulation Tp*MoX(pterin-R-dithiolene) (Tp* = tris(3,5,-dimethylpyrazolyl)borate), X= O, S, R= aryl or −C(OH)(CH 3 ) 2 ). Syntheses of Mo(4+) and (5+) complexes of two pterin-dithiolene derivatives as both oxo and sulfido compounds, and improved syntheses for pterinyl alkynes and [Et 4 N][Tp*Mo IV (S)S 4 ] reagents are described. Characterization methods include electrospray ionization mass spectrometry, electrochemistry, infrared spectroscopy, electron paramagnetic resonance and magnetic circular dichroism. Cyclic voltammetry reveals that the Mo(5+/4+) reduction potential is intermediate between that for dithiolene with electron-withdrawing substituents and simple dithiolate chelates. Electron paramagnetic resonance and magnetic circular dichroism of Mo(5+) complexes where X = O, R = aryl indicates that the molybdenum environment in the new models is electronically similar to that in Tp*MoO(benzenedithiolate).