New Role for Radical SAM Enzymes in the Biosynthesis of Thio(seleno)oxazole RiPP Natural Products.

Ribosomally synthesized post-translationally modified peptides (RiPPs) are ubiquitous and represent a structurally diverse class of natural products. The ribosomally encoded precursor polypeptides are often extensively modified post-translationally by enzymes that are encoded by coclustered genes. Radical S-adenosyl-l-methionine (SAM) enzymes catalyze numerous chemically challenging transformations. In RiPP biosynthetic pathways, these transformations include the formation of C-H, C-C, C-S, and C-O linkages. In this paper, we show that the Geobacter lovleyi sbtM gene encodes a radical SAM protein, SbtM, which catalyzes the cyclization of a Cys/SeCys residue in a minimal peptide substrate. Biochemical studies of this transformation support a mechanism involving H-atom abstraction at the C-3 of the substrate Cys to initiate the chemistry. Several possible cyclization products were considered. The collective biochemical, spectroscopic, mass spectral, and computational observations point to a thiooxazole as the product of the SbtM-catalyzed modification. To our knowledge, this is the first example of a radical SAM enzyme that catalyzes a transformation involving a SeCys-containing peptide and represents a new paradigm for formation of oxazole-containing RiPP natural products.

Molecular and Electronic Structures and Single-Molecule Magnet Behavior of Tris(thioether)-Iron Complexes Containing Redox-Active α-Diimine Ligands.

Incorporating radical ligands into metal complexes is one of the emerging trends in the design of single-molecule magnets (SMMs). While significant effort has been expended to generate multinuclear transition metal-based SMMs with bridging radical ligands, less attention has been paid to mononuclear transition metal-radical SMMs. Herein, we describe the first α-diiminato radical-containing mononuclear transition metal SMM, namely, [κ2-PhTttBu]Fe(AdNCHCHNAd) (1), and its analogue [κ2-PhTttBu]Fe(CyNCHCHNCy) (2) (PhTttBu = phenyltris(tert-butylthiomethyl)borate, Ad = adamantyl, and Cy = cyclohexyl). 1 and 2 feature nearly identical geometric and electronic structures, as shown by X-ray crystallography and electronic absorption spectroscopy. A more detailed description of the electronic structure of 1 was obtained through EPR and Mössbauer spectroscopies, SQUID magnetometry, and DFT, TD-DFT, and CAS calculations. 1 and 2 are best described as high-spin iron(II) complexes with antiferromagnetically coupled α-diiminato radical ligands. A strong magnetic exchange coupling between the iron(II) ion and the ligand radical was confirmed in 1, with an estimated coupling constant J < -250 cm-1 (J = -657 cm-1, DFT). Calibrated CAS calculations revealed that the ground-state Fe(II)-α-diiminato radical configuration has significant ionic contributions, which are weighted specifically toward the Fe(I)-neutral α-diimine species. Experimental data and theoretical calculations also suggest that 1 possesses an easy-axis anisotropy, with an axial zero-field splitting parameter D in the range from -4 to-1 cm-1. Finally, dynamic magnetic studies show that 1 exhibits slow magnetic relaxation behavior with an energy barrier close to the theoretical maximum, 2|D|. These results demonstrate that incorporating strongly coupled α-diiminato radicals into mononuclear transition metal complexes can be an effective strategy to prepare SMMs.

Perception of the plant hormone ethylene: known-knowns and known-unknowns.

The gaseous phytohormone ethylene is implicated in virtually all phases of plant growth and development and thus has a major impact on crop production. This agronomic impact makes understanding ethylene signaling the Philosopher's Stone of the plant biotechnology world in applications including post-harvest transport of foodstuffs, consistency of foodstuff maturity pre-harvest, decorative flower freshness and longevity, and biomass production for biofuel applications. Ethylene is biosynthesized by plants in response to environmental factors and plant life-cycle events, and triggers a signaling cascade that modulates over 1000 genes. The key components in the perception of ethylene are a family of copper dependent receptors, the bioinorganic chemistry of which has been largely ignored by the chemical community. Since identification of these receptors two decades ago, there has been tremendous growth in knowledge in the biological community on the signal transduction pathways and mechanisms of ethylene signaling. In this review, we highlight these advances and key chemical voids in knowledge that are overdue for exploration, and which are required to ultimately regulate and control ethylene signaling.

Dioxygen activation at monovalent nickel.

The monovalent oxidation state of nickel has received a growing amount of attention in recent years, in part due to its suggested catalytic role in a number of metalloprotein-mediated transformations. In coordination chemistry, nickel(I) is suitable for reductive activation of dioxygen, provided ligands are used that stabilize this less common oxidation state against disproportionation reactions. Two distinct molecular systems have been explored, which have provided access to new nickel-dioxygen structure types, namely, monomeric side-on and end-on superoxo and trans-micro-1,2-peroxo-dinickel complexes. The geometric and electronic structures of the complexes have been established by advanced spectroscopic methods, including resonance Raman and X-ray absorption spectroscopies, and augmented by density functional theory analyses.

Identification of an "end-on" nickel-superoxo adduct, [Ni(tmc)(O2)]+.

An "end-on" Ni2+-superoxo adduct has been prepared via two independent synthetic routes and its structure ascertained by spectroscopic and computational methods. The new structure type in nickel coordination chemistry is supported by resonance Raman and EPR spectroscopic features, the former displaying a high frequency nu (O-O) mode (1131 cm-1) consistent with significant superoxo character. The Ni2+-superoxo adduct oxidizes PPh3 to OPPh3 in quantitative yield.

Spectroscopic and computational studies on the trans-mu-1,2-peroxo-bridged dinickel(II) species [{Ni(tmc)}2 (O2)](OTf)2: nature of end-on peroxo-nickel(II) bonding and comparison with peroxo-copper(II) bonding.

Resonance Raman (rR) spectroscopic and density functional theory (DFT) computational studies on a trans-mu-1,2-peroxo-bridged (Ni2+)2 complex, [{(tmc)Ni2+}2 (O2)]2+ (1, tmc = 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane), are presented and discussed. These studies afford a detailed description of the geometric and electronic structures of the Ni2O2 core in 1 and provide a suitable basis for a quantitative comparison between Ni-peroxo and Cu-peroxo bonding. From a normal coordinate analysis of rR data of 1, values of k(Ni-O) = 1.52 mdyn/A and k(O-O) = 2.58 mdyn/A are obtained for the Ni-O and O-O stretch force constants, respectively, which are considerably smaller than k(Cu-O) = 2.05 mdyn/A and k(O-O) = 3.09 mdyn/A reported for a representative trans-mu-1,2-peroxo-bridged (Cu2+)2 complex, [{(TMPA)Cu2+}2 (O2)]2+. These differences primarily reflect a strongly reduced covalency of the metal-peroxo bonds in 1 relative to the (Cu2+)2 dimer as a result of the lower effective nuclear charge of Ni2+ than Cu2+. DFT computations aimed at elucidating the reaction coordinate for the thermal decay of 1 reveal that the conversion of this species to a side-on peroxo (Ni2+)2 dimer is electronically feasible but energetically unfavorable by approximately 85 kcal/mol due to the steric constraints imposed by the tmc supporting ligands. These results suggest that the decay of 1 to the crystallographically characterized final product, [(tmc)Ni2+ OH]OTf, proceeds without initial end-on --> side-on peroxo (Ni2+)2 core conversion.