Hydride Reduction of NAD(P)⁺ Model Compounds with a Ru(II)–Hydrido Complex

Abstract

In order to better understand the regioselective hydride transfer of metal hydrido complexes to NAD(P) + model compounds, reactions of [Ru(tpy)(bpy)H] + (Ru-H: tpy = 2,2′:6″,2″-terpyridine, bpy = 2,2′-bipyridine) with various substituent NAD(P) + model compounds were investigated in detail. All of the NAD(P) + model compounds accepted hydride from Ru-H, yielding 1:1 adducts, where the dihydro form(s) of the model compounds coordinated with the carbamoyl group to the Ru(II) center of [Ru(tpy)(bpy)] 2+ , with very different reaction rates. Some reactions produced the adduct with only the 1,4-dihydro structure, whereas others produced a mixture of two adducts, with a 1,4-or 1,2-dihydro structure. In particular, temperature-dependent adduct formation kinetics studies provided important information on the transition state(s) of the hydride transfer reactions and factors for determining the regioselectivity. Most adducts were cleaved to the corresponding free dihydro product(s) with the same distribution of the regioisomers to the adduct(s).

Hydride Transfer from Iron(II) Hydride Compounds to NAD(P)+ Analogues

“…In conclusion, we investigated the reactions between iron­(II) hydride compounds of Cp*­(P-P)­FeH and NAD + analogues. Unlike reported Ru II –H cases, , there were no interactions between Fe II –H and BNA + analogues observed during H – transfer reactions. Kinetics studies suggest that the BNA + model is reduced at the C6 position, affording 1,6-BNAH, which is converted to the more thermally stable 1,4-product.…”

“…Furthermore, [Cp*Fe­(P-P)­(1,4-BzPy H -CN)] + released 1,4-BzPy H -CN in MeCN to afford [Cp*­(P-P)­Fe­(NCMe)] + , and finally an reaction equilibrium was observed, judging from NMR spectral studies (Figures S44–S47 in the Supporting Information). Though a H – transfer mechanism based on coordination or interaction between pyridinium salts to Ru and Rh hydride complexes was considered, − the reaction path depicted in eq cannot be excluded for BzPy-CN + and Cp*­(P-P)­FeH. …”

“…This transition state could cause the C4 position to be more electrophilic toward attack. Ishitani et al reported the interactions between [(tpy)­(bpy)­RuH] + (tpy = 2,2′:6′2″-terpyridine) and BNA + salts, forming a [Ru-BNAH] + adduct . However, such interactions have also been observed in NMR studies, even in pyridinium salts with a noncoordinating group at the C3 position.…”

“…Although hydrides (M–H) based on noble metals (M = Ru, − ,− Ir, Rh , ) have been well investigated in this field, studies based on abundant metal hydrides are sparse. In recent years, remarkable progress has been made in hydrogenation and transfer hydrogenation catalysis by first- and second-row metals. , We have been interested in the reduction of NAD + cation models by using hydrido iron­(II) complexes, and previous work with Rauchfuss et al has demonstrated the hydridic character of a diiron dihydride compound toward benzimidazolium salts …”

Ligand Conjugation Directs the Formation of a 1,3-Dihydropyridinate Regioisomer

“…The role of the protein environment surrounding DHPs, the mechanism of DHP reaction chemistry, and the role of the DHP side chains have been probed, and model systems for these efforts, including dihydrofolate reductase and aldehyde dehydrogenases, have been studied in detail. Along with these ongoing efforts in biological systems, there is significant scope to enhance our understanding of organohydride chemistry via synthetic approaches. − …”