Electrophilic Species Research Articles

Chemical Priming by Isothiocyanates Protects Against Intoxication by Products of the Mustard Oil Bomb.

In Brassicaceae, tissue damage triggers the mustard oil bomb i.e., activates the degradation of glucosinolates by myrosinases leading to a rapid accumulation of isothiocyanates at the site of damage. Isothiocyanates are reactive electrophilic species (RES) known to covalently bind to thiols in proteins and glutathione, a process that is not only toxic to herbivores and microbes but can also cause cell death of healthy plant tissues. Previously, it has been shown that subtoxic isothiocyanate concentrations can induce transcriptional reprogramming in intact plant cells. Glutathione depletion by RES leading to breakdown of the redox potential has been proposed as a central and common RES signal transduction mechanism. Using transcriptome analyses, we show that after exposure of Arabidopsis seedlings (grown in liquid culture) to subtoxic concentrations of sulforaphane hundreds of genes were regulated without depletion of the cellular glutathione pool. Heat shock genes were among the most highly up-regulated genes and this response was found to be dependent on the canonical heat shock factors A1 (HSFA1). HSFA1-deficient plants were more sensitive to isothiocyanates than wild type plants. Moreover, pretreatment of Arabidopsis seedlings with subtoxic concentrations of isothiocyanates increased resistance against exposure to toxic levels of isothiocyanates and, hence, may reduce the autotoxicity of the mustard oil bomb by inducing cell protection mechanisms.

DFT studies on vibrational and electronic spectra, HOMO–LUMO, MEP, HOMA, NBO and molecular docking analysis of benzyl-3-N-(2,4,5-trimethoxyphenylmethylene)hydrazinecarbodithioate

Benzyl-3-N-(2,4,5-trimethoxyphenylmethylene)hydrazinecarbodithioate (compound 1) is a bidentate and nitrogen-sulfur containing Schiff base, which has been synthesized by the condensation reaction of S-benzylndithiocarbazate and 2,4,5-trimethoxybenzaldehyde. The theoretical calculations of the mentioned compound have been carried out using the more popular density functional theory method, Becke-3-Parameter-Lee-Yang-Parr (B3LYP) in 6-31G+(d,p) basis set. The computational results of the compound were compared with the obtained experimental value. Moreover, the highest occupied molecular orbital, the lowest unoccupied molecular orbital, molecular electrostatic potential, chemical reactivity parameters and natural bond orbital of the optimized structure have been evaluated at the same level of theory. Furthermore, the UV–Vis spectrum of the compound has been carried out for the better understanding of electronic absorption spectra with the help of the time-dependent density functional theory at room temperature. Besides, the molecular docking simulation of the mentioned molecule with target protein was also investigated. In addition, in silico studies were performed to predict absorption, distribution, metabolism, excretion and toxicity profiles of the designed compound. The results indicated that the theoretical data have well correlated with the observed values. The narrow frontier orbital gap indicated that the eventual charge transfer interaction occurs within the studied molecule and showed high chemical reactivity. The global reactivity values showed that the compound is soft molecule, electrophilic species and has strong binding ability with biomolecules. The molecular electrostatic potential structure indicated that the negative and positive potential sites are around electronegative atoms and hydrogen atoms of studied compound, respectively. The natural bond orbital data revealed that the compound contains 97.42% Lewis and 2.58% non-Lewis structure. The intra and inter-molecular charge transfers process occur within the studied compound. The studied compound showed more binding energy (−6.0 kcal/mol) with target protein than hydroxychloroquine (−5.6 kcal/mol). The absorption, distribution, metabolism, excretion and toxicity investigation predicted that the compound has good drug like character.

RES transformation for biosynthesis and detoxification.

The reactive electrophilic species (RES), typically the molecules bearing α,β-unsaturated carbonyl group, are widespread in living organisms and notoriously known for their damaging effects. Many of the mycotoxins released from phytopathogenic fungi are RES and their contamination to cereals threatens food safety worldwide. However, due to their high reactivity, RES are also used by host organisms to synthesize specific metabolites. The evolutionary conserved glyoxalase (GLX) system scavenges the cytotoxic α-oxoaldehydes that bear RES groups, which cause host disorders and diseases. In cotton, a specialized enzyme derived from glyoxalase I (GLXI) through gene duplications and named as specialized GLXI (SPG), acts as a distinct type of aromatase in the gossypol pathway to transform the RES intermediates into the phenolic products. In this review, we briefly introduce the research progress in understanding the RES, especially the RES-type mycotoxins, the GLX system and SPG, and discuss their application potential in detoxification and synthetic biology.

Supramolecular Assembly of Metal Complexes by (Aryl)I⋅⋅⋅d [PtII ] Halogen Bonds.

The theoretical data for the half-lantern complexes [{Pt( )(μ- )}2 ] [1-3; is cyclometalated 2-Ph-benzothiazole; is 2-SH-pyridine (1), 2-SH-benzoxazole (2), 2-SH-tetrafluorobenzothiazole (3)] indicate that the Pt⋅⋅⋅Pt orbital interaction increases the nucleophilicity of the outer d orbitals to provide assembly with electrophilic species. Complexes 1-3 were co-crystallized with bifunctional halogen bonding (XB) donors to give adducts (1-3)2 ⋅(1,4-diiodotetrafluorobenzene) and infinite polymeric [1⋅1,1'-diiodoperfluorodiphenyl]n . X-ray crystallography revealed that the supramolecular assembly is achieved through (Aryl)I⋅⋅⋅d [PtII ] XBs between iodine σ-holes and lone pairs of the positively charged (PtII )2 centers acting as nucleophilic sites. The polymer includes a curved linear chain ⋅⋅⋅Pt2 ⋅⋅⋅I(areneF )I⋅⋅⋅Pt2 ⋅⋅⋅ involving XB between iodine atoms of the perfluoroarene linkers and (PtII )2 moieties. The 195 Pt NMR, UV/Vis, and CV studies indicate that XB is preserved in CH(D)2 Cl2 solutions.

The effect of the Ce content on the oxidative dehydrogenation of propane over CrO -CeO2/γ-Al2O3 catalysts

A series of CrO y (17.5 wt%)-CeO 2 ( X wt%)/γ-Al 2 O 3 catalysts ( X = 0, 0.5, 2, 5, 8) with various Ce contents were prepared by a wetness impregnation method and were applied to the dehydrogenation of propane to propylene at 550 °C and 0.1 MPa. The prepared catalysts were characterized by BET, H 2 -TPR, O 2 -TPD, XPS, XRD, SEM-EDS and Raman spectroscopy. Among the prepared catalysts, the 17.5Cr-2Ce/Al catalyst with the largest amount of lattice oxygen exhibited the best catalytic performance for the dehydrogenation of propane to propylene with lattice oxygen. The decreased presence of oxygen defects and reducibility were the factors responsible for the improved dehydrogenation activity of the catalysts. The CeO 2 layer could inhibit the evolution of lattice oxygen (O 2− ) to electrophilic oxygen species (O 2 − ), and the oxygen defects on the catalyst surface were reduced. The inhibited lattice oxygen evolution prevented the deep oxidation of propane or propylene, the average CO x selectivity decreased from 24.41% (17.5Cr/Al) to 5.71% (17.5Cr-2Ce/Al), and the average propylene selectivity increased from 60.15% (17.5Cr/Al) to 85.05% (17.5Cr-2Ce/Al).

Novel triplet silavinylidenes via density functional theory

AbstractFollowing our quest for novel triplet silylenes, we have compared and contrasted electronic effects on 5‐silavinylidenyl‐1,4‐diX‐tetrazoles with XH, CH3, OCH3, NH2, NMe2, OH, CN, Cl, CF3, and F (1–10, respectively), at M06/6‐311++G** level of theory. Six structures with XH (1) and electron‐donating groups (EDGs, 2–6) appear triplet while the other four with electron‐withdrawing groups (EWGs, 7–10) show singlet ground states. The overall trend for triplet stability based on their ΔEs‐t is 1 > 2 > 3 > 4 > 5 > 6 > 7 > 8 > 9 > 10. The EWGs increase electrophilicity (ω) making 7 (7.09 eV) as the most electrophilic species. In contrast, EDGs increase nucleophilicity (N) showing 5 (5.47 eV) and 8 (3.18 eV) as the most and least nucleophilic silylenes, respectively. Moreover, 5 and 8 show the highest and lowest chemical potential (μ = −3.14 and −5.29 eV, respectively). In addition, 5 displays the highest energies of HOMO (EHOMO = −4.02 eV) and LUMO (ELUMO = −2.27 eV) and the lowest ω (2.82 eV) among the scrutinized species.

Kitamura Electrophilic Fluorination Using HF as a Source of Fluorine.

This review article focused on the innovative procedure for electrophilic fluorination using HF and in situ generation of the required electrophilic species derived from hypervalent iodine compounds. The areas of synthetic application of this approach include fluorination of 1,3-dicarbonyl compounds, aryl-alkyl ketones, styrene derivatives, α,β-unsaturated ketones and alcohols, homoallyl amine and homoallyl alcohol derivatives, 3-butenoic acids and alkynes.

Is Isoeugenol a Prehapten? Characterization of a Thiol-Reactive Oxidative Byproduct of Isoeugenol and Potential Implications for Skin Sensitization.

Isoeugenol is widely used by the cosmetic and fragrance industries, but it also represents a known cause of skin sensitization adverse effects. Although devoid of a structural alert, isoeugenol has been classified as prehapten in virtue of the presence of a pre-Michael acceptor domain. Isoeugenol oxidation could theoretically lead to the generation of reactive toxic quinones, and photoinduced oxidative degradation of isoeugenol was reported to generate strongly thiol reactive byproducts. Nonetheless, the isoeugenol degradation product responsible for increased reactivity was found to be elusive. In the present study, an aged isoeugenol sample was subjected to reactivity-guided experiments to trap elusive thiol reactive species with a fluorescent nucleophile, viz. dansyl cysteamine (DCYA). The results herein presented demonstrate that photo-oxidation of isoeugenol led to the formation of a dimeric 7,4'-oxyneolignan with strong chemical reactivity, capable of nucleophilic substitution with thiols. The results were confirmed by isolation, structural characterization, and further NMR reactivity studies. Isoeugenol is already well-known as moderately reactive in thiol depletion assays, and was herein demonstrated to be capable of converting to more potent electrophilic species upon degradation, thus acting as a prehapten. The application of the reactivity-guided strategy described herein was shown to serve as an effective tool to investigate elusive skin sensitizers.

Acid-Promoted Intramolecular Decarbonylative Coupling Reactions of Unstrained Ketones: A Modular Approach to Synthesis of Acridines and Diaryl Ketones.

Herein, we reported Lewis acid- or Brønsted acid-promoted intramolecular C(sp2)-C(sp2) bond cleavage and a novel C(sp2)-C(sp2) bond-forming cascade reaction to synthesize the acridine motif. The metal-free oxidation of the alkyne motif generated the in situ ketone group extracted via a decarbonylation reaction. The mechanistic studies revealed that the electrophilic N-iodo species triggered key decarbonylation reactions via consecutive dearomatization/aromatization reactions. In addition, we exploited this acid-promoted C-C bond activation system with internal alkynes to synthesize bis(heteroaryl) ketones.

Selenocystine Peptides Performance in 5‐endo‐dig Reactions

Herein, we present methods for the generation of selenocysteinyl electrophile by weak Lewis acids or oxidants. The electrophilic selenium species were further utilized in 5‐endo‐dig cyclization reactions with 2‐ethynyl phenols, anisoles, and anilines, yielding substituted benzo[b]furans and indoles bearing short selenocysteine‐containing peptides. Copper(II) bromide promoted 5‐endo‐dig cyclization can be successfully applied for protected and unprotected peptides in high yields. Elaborated protocol allows the construction of phenylindeno[1,2‐c]chromene moiety in 5‐endo‐dig/6‐endo‐dig cascade reactions.

Hexamethylphosphanetriamine‐mediated aziridination of imines with alpha‐ketoesters: A molecular electron density theory study

AbstractThe highly trans‐stereoselective reaction of oxyphosphonium enolate (OPE) with N‐benzylidene‐4‐methoxybenzenesulfonamide (N‐BMS) in toluene, at room temperature leading to trans‐aziridine‐2‐carboxylate (trans‐Az 3), was theoretically studied using molecular electron density theory (MEDT) at the B3LYP/6‐31G(d) computational level to shed light on the energy transformation, selectivities, and mechanistic aspects. This domino process is initialized by adding of N,N,N′,N′,N″,N″‐hexamethylphosphanetriamine (HMPT) to methyl benzoylformate to generate OPE. Subsequently, nucleophilic addition of OPE to the C–N double bond in N‐BMS leads to the intermediate IN‐Ta. Finally, trans‐Az 3 is formed through a 3‐exo‐tet ring closure step as a result of the nucleophilic attack of the negatively charged nitrogen atom on the carbon atom bearing –OP (NMe2)3 in IN‐Ta. Analysis of the relative Gibbs free energies shows that the ring closure step is the rate‐determining step. By an investigation of the conceptual density functional theory reactivity indices, OPE and N‐BMS are classified as a strong nucleophilic and as a strong electrophilic species, respectively, which indicates that the additional step of OPE to N‐BMS should display a high‐polar character. An analysis of the calculated electrophilic and nucleophilic Parr functions at the reactive sites of reagents clarifies the regioselectivity observed experimentally along the C1–C2 bond formation process.

Eco‐friendly synthesis of novel pyrimidine derivatives as potential anticancer agents

AbstractHerein, a rapid and highly efficient method for the synthesis of a new series of pyrimidine derivatives was demonstrated. The strategy was emanated from the reaction of hydrazinyl pyrimidine derivative (1) with different electrophilic species such as ethyl acetoacetate, ethyl 4,4,4‐trifluoro acetoacetate, and phenyl isothiocyanate following cyclocondensation mechanism to afford the corresponding derivatives (2‐6). Furthermore, condensation of hydrazine derivative (1) with different carbonyl compounds via conventional heating and microwave irradiation conditions was employed as a source of Schiff base derivatives bearing pyrimidine moiety (7‐12). The structural features of all newly synthesized compounds were characterized by elemental and spectroscopic evidences. Some of the synthesized compounds were evaluated for in vitro cytotoxicity. The preliminary screening results showed that most of the tested compounds have moderate cytotoxic activity against HepG2 and HCT‐116 cell lines. Finally, a molecular docking study was conducted to reveal the probable interaction with the thymidylate synthase enzyme.

The non-photochemical quenching protein LHCSR3 prevents oxygen-dependent photoinhibition in Chlamydomonas reinhardtii

Non-photochemical quenching (NPQ) helps dissipate surplus light energy, preventing formation of reactive oxygen species (ROS). In Chlamydomonas reinhardtii, the thylakoid membrane protein LHCSR3 is involved in pH-dependent (qE-type) NPQ, lacking in the npq4 mutant. Preventing PSII repair revealed that npq4 lost PSII activity faster than the wild type (WT) in elevated O2, while no difference between strains was observed in O2-depleted conditions. Low Fv/Fm values remained 1.5 h after moving cells out of high light, and this qH-type quenching was independent of LHCSR3 and not accompanied by losses of maximum PSII activity. Culturing cells in historic O2 atmospheres (30-35%) increased the qE of cells, due to increased LHCSR1 and PsbS levels, and LHCSR3 in the WT, showing that atmospheric O2 tensions regulate qE capacity. Colony growth of npq4 was severely restricted at elevated O2, and npq4 accumulated more reactive electrophile species (RES) than the WT, which could damage PSI. Levels of PsaA (PSI) were lower in npq4 grown at 35% O2, while PsbA (PSII) levels remained stable. We conclude that even at high O2 concentrations, the PSII repair cycle is sufficient to maintain net levels of PSII. However, LHCSR3 has an important function in protecting PSI against O2-mediated damage, such as via RES.

Graphitic nanosheets via two-dimensional polymerization enhancing organic all-optically controlled photorefractive performance

All-optically controlled devices are the attractive subjects due to their future applications in all-optically controlled networks and computers. In this work, two-dimensional (2D) graphite nanosheets are synthesized to improve organic photorefractive performance in the all-optical operation, i.e., the photorefractive performance under zero electric field. The synthetic process is performed by 2D-polymerizing electrophilic and nucleophilic carbon species under solvothermal effect, where [:C≡C:]2− in calcium carbide is applied as nucleophilic carbon species and [C(Cl)] in carbon tetrachloride (CCl4) as electrophilic carbon species. The polycarbonization reaction consists of 1D horizontal growth for nanoribbon and 2D vertical growth for single-layer graphene. Then, single-layer graphene nanosheets are aggregated via π–π stacking effect into 2D graphite nanosheets being composed of multilayer graphene nanosheets. Notably, the self-template characteristics induce the synchronous and alternate ongoing of three above processes. Interestingly, when these 2D graphite nanosheets are doped into organic photorefractive devices, the all-optically controlled photorefractive performance is effectively improved by enhancing the gain coefficient of two-beam coupling about 46.4% from 80.1 cm−1 of control device to 117.2 cm−1 of nanographite-doped device. This is attributed to the excellent electric conductance of 2D graphite nanosheets, which strengthens the charge separation under the nonuniform light field inside organic photorefractive devices. Then, the stronger built-in electric field will be induced so that the orientation enhancement effect is increased in organic photorefractive devices. This work provides an effective and facile approach to improve organic all-optically controlled photorefractive performance with 2D graphitic nanosheets.

Synthesis of 3-selanylbenzo[b]furans promoted by SelectFluor®.

A simple and practical protocol for the synthesis of 3-selanyl-benzo[b]furans mediated by the SelectFluor® reagent was developed. This novel methodology provided a greener alternative to generate 3-substituted-benzo[b]furans via a metal-free procedure under mild conditions. The intramolecular cyclization reaction was carried out employing an electrophilic selenium species generated in situ through the reaction between SelectFluor® and organic diselenides. The formation of this electrophilic selenium species (RSe-F) was confirmed by heteronuclear NMR spectroscopy, and its reactivity was explored.

Refined bounds on MeV-scale thermal dark sectors from BBN and the CMB

New light states thermally coupled to the Standard Model plasma alter the expansion history of the Universe and impact the synthesis of the primordial light elements. In this work, we carry out an exhaustive and precise analysis of the implications of MeV-scale BSM particles in Big Bang Nucleosynthesis (BBN) and for Cosmic Microwave Background (CMB) observations. We find that BBN observations set a lower bound on the thermal dark matter mass of mχ > 0.4 MeV at 2σ. This bound is independent of the spin and number of internal degrees of freedom of the particle, of the annihilation being s-wave or p-wave, and of the annihilation final state. Furthermore, we show that current BBN plus CMB observations constrain purely electrophilic and neutrinophilic BSM species to have a mass, mχ > 3.7 MeV at 2σ. We explore the reach of future BBN measurements and show that upcoming CMB missions should improve the bounds on light BSM thermal states to mχ > (10−15) MeV. Finally, we demonstrate that very light BSM species thermally coupled to the SM plasma are highly disfavoured by current cosmological observations.

The antitumour activity of 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole in human gastric cancer models is mediated by AhR signalling.

Stomach cancer is the fourth most common cancer worldwide. Identification of novel molecular therapeutic targets and development of novel treatments are critical. Against a panel of gastric carcinoma cell lines, the activity of 2‐(4‐amino‐3‐methylphenyl)‐5‐fluorobenzothiazole (5F 203) was investigated. Adopting RT‐PCR, Western blot and immunohistochemical techniques, we sought to determine molecular pharmacodynamic (PD) markers of sensitivity and investigate arylhydrocarbon (AhR) receptor‐mediated signal transduction activation by 5F 203. Potent (IC50 ≤ 0.09 μmol/L), selective (>250‐fold) in vitro antitumour activity was observed in MKN‐45 and AGS carcinoma cells. Exposure of MKN‐45 cells to 5F 203 triggered cytosolic AhR translocation to nuclei, inducing CYP1A1 (>50‐fold) and CYP2W1 (~20‐fold) transcription and protein (CYP1A1 and CYP2W1) expression. G2/M arrest and γH2AX expression preceded apoptosis, evidenced by PARP cleavage. In vivo, significant (P < .01) 5F 203 efficacy was observed against MKN‐45 and AGS xenografts. In mice‐bearing 5F 203‐sensitive MKN‐45 and 5F 203‐insensitive BGC‐823 tumours in opposite flanks, CYP1A1, CYP2W1 and γH2AX protein in MKN‐45 tumours only following treatment of mice with 5F 203 (5 mg/kg) revealed PD biomarkers of sensitivity. 5F 203 evokes potent, selective antitumour activity in vitro and in vivo in human gastric cancer models. It triggers AhR signal transduction, CYP‐catalysed bioactivation to electrophilic species causing lethal DNA double‐strand breaks exclusively in sensitive cells. 5F 203 represents a novel therapeutic agent with a mechanism of action distinct from current clinical drugs, exploiting novel molecular targets pertinent to gastric tumourigenesis: AhR, CYP1A1 and CYP2W1. PD markers of 5F 203 sensitivity that could guide patient selection have been identified.

12-Oxophytodienoic Acid Reductase 3 (OPR3) Functions as NADPH-Dependent α,β-Ketoalkene Reductase in Detoxification and Monodehydroascorbate Reductase in Redox Homeostasis

Arabidopsis (Arabidopsis thaliana) 12-oxophytodienoic acid reductase isoform 3 (OPR3) is involved in the synthesis of jasmonic acid (JA) by reducing the α,β-unsaturated double bond of the cyclopentenone moiety in 12-oxophytodienoic acid (12-OPDA). Recent research revealed that JA synthesis is not strictly dependent on the peroxisomal OPR3. The ability of OPR3 to reduce trinitrotoluene suggests that the old yellow enzyme homolog OPR3 has additional functions. Here, we show that OPR3 catalyzes the reduction of a wide spectrum of electrophilic species that share a reactivity toward the major redox buffers glutathione (GSH) and ascorbate (ASC). Furthermore, we show that 12-OPDA reacts with ASC to form an ASC-12-OPDA adduct, but in addition OPR3 has the ability to regenerate ASC from monodehydroascorbate. The presented data characterize OPR3 as a bifunctional enzyme with NADPH-dependent α,β-ketoalkene double-bond reductase and monodehydroascorbate reductase activities (MDHAR). opr3 mutants showed a slightly less-reduced ASC pool in leaves in line with the MDHAR activity of OPR3 in vitro. These functions link redox homeostasis as mediated by ASC and GSH with OPR3 activity and metabolism of reactive electrophilic species.

Preparation of LaAlO3 perovskite catalysts by simple solid-state method for oxidative coupling of methane

Abstract The preparation of LaAlO3 perovskite catalysts for the oxidative coupling of methane (OCM) using a very simple solid-state method with good reproducibility is described. To obtain high performance LaAlO3 catalysts, preparation conditions such as time, temperature, and oxygen content, which have a strong effect on the catalytic activity, are controlled during the calcination process. As the calcination time and temperature increase, the catalytic activity of LaAlO3 improves due to the good homogeneity and high crystallinity of LaAlO3 perovskite. Especially, the LaAlO3 catalyst calcined at 1350 °C for 24 h shows the highest selectivity and yield of C2 hydrocarbons. LaAlO3 catalysts calcined at various oxygen fractions show a volcano-shaped curve with respect to oxygen content in calcination gas, and the LaAlO3 catalyst prepared with an oxygen content of 5 % exhibits the best catalytic performance in this reaction. The appropriate oxygen fraction provides the LaAlO3 catalyst with a large amount of electrophilic lattice oxygen species and a sufficient amount of adsorption oxygen species, which are known to play key roles in the OCM reaction. This study clearly reveals this simple, highly reproducible, and mass-productive solid-state method as a promising preparation method for high performance LaAlO3 perovskite catalysts for OCM.

Mechanism of Os-Catalyzed Oxidative Cyclization of 1,5-Dienes.

The oxidative cyclization of 1,5-dienes by metal-oxo species is a powerful method for stereocontrolled synthesis of tetrahydrofuran diols (THF-diols), structural motifs present in many bioactive natural products. Oxidative cyclization of (2E,6E)-octa-2,6-diene catalyzed by OsO4/NMO has been studied using density functional theory (DFT) calculations (M06-2X/aug-cc-pVDZ/Hay-Wadt VDZ (n+1) ECP), highlighting the remarkable effect of acid on the fate of the first intermediate, an Os(VI) dioxoglycolate. A strong acid promotes cyclization of the Os(VI) dioxoglycolate, or its NMO complex, through protonation of an oxo ligand to give more electrophilic species. By contrast, in the absence of acid, reoxidation may occur to afford the Os(VIII) trioxoglycolate, which is shown to favor conventional "second cycle" dihydroxylation reactivity rather than cyclization. The results of the calculations are consistent with experimental results for reactions of OsO4/NMO with 1,5-dienes with acid (oxidative cyclization) and without acid (second cycle osmylation/dihydroxylation). Detailed evaluation of potential catalytic cycles supports oxidation of the cyclized Os(IV) THF-diolate intermediate to the corresponding Os(VI) species followed by slow hydrolysis and, finally, regeneration of OsO4.