Modified cyclodextrins solubilize elemental sulfur in water and enable biological sulfane sulfur delivery

An important form of biological sulfur is sulfane sulfur, or S⁰, which is found in polysulfide and persulfide compounds as well as in elemental sulfur. Sulfane sulfur, often in the form of S₈, functions as a key energy source in the metabolic processes of thermophilic Archaean organisms found in sulfur-rich environments and can be metabolized both aerobically and anaerobically by different archaeons. Despite this importance, S₈ has a low solubility in water (∼19 nM), raising questions of how it can be made chemically accessible in complex environments. Motivated by prior crystallographic data showing S₈ binding to hydrophobic motifs in filamentous glycoproteins from the sulfur reducing Staphylothermus marinus anaerobe, we demonstrate that simple macrocyclic hydrophobic motifs, such as 2-hydroxypropyl β-cyclodextrin (2HPβ), are sufficient to solubilize S₈ at concentrations up to 2.0 ± 0.2 mM in aqueous solution. We demonstrate that the solubilized S₈ can be reduced with the common reductant tris(2-carboxyethyl)phosphine (TCEP) and reacts with thiols to generate H₂S. The thiol-mediated conversion of 2HPβ/S₈ to H₂S ranges from 80% to quantitative efficiency for Cys and glutathione (GSH). Moreover, we demonstrate that 2HPβ can catalyze the Cys-mediated reduction of S₈ to H₂S in water. Adding to the biological relevance of the developed systems, we demonstrate that treatment of Raw 264.7 macrophage cells with the 2HPβ/S₈ complex prior to LPS stimulation decreases NO₂⁻ levels, which is consistent with known activities of bioavailable H₂S and sulfane sulfur. Taken together, these investigations provide a new strategy for delivering H₂S and sulfane sulfur in complex systems and more importantly provide new insights into the chemical accessibility and storage of S⁰ and S₈ in biological environments.

Sulfane sulfur, or S⁰, is found in polysulfide and persulfide compounds in biology. We demonstrate that modified cyclodextrins can solubilize S₈ in water, increase its reactivity with biological nucleophiles, and enable delivery to live cells.     

Proton-conductive coordination polymer glass for solid-state anhydrous proton batteries

Designing solid-state electrolytes for proton batteries at moderate temperatures is challenging as most solid-state proton conductors suffer from poor moldability and thermal stability. Crystal–glass transformation of coordination polymers (CPs) and metal–organic frameworks (MOFs) via melt-quenching offers diverse accessibility to unique properties as well as processing abilities. Here, we synthesized a glassy-state CP, [Zn₃(H₂PO₄)₆(H₂O)₃](1,2,3-benzotriazole), that exhibited a low melting temperature (114 °C) and a high anhydrous single-ion proton conductivity (8.0 × 10⁻³ S cm⁻¹ at 120 °C). Converting crystalline CPs to their glassy-state counterparts via melt-quenching not only initiated an isotropic disordered domain that enhanced H⁺ dynamics, but also generated an immersive interface that was beneficial for solid electrolyte applications. Finally, we demonstrated the first example of a rechargeable all-solid-state H⁺ battery utilizing the new glassy-state CP, which exhibited a wide operating-temperature range of 25 to 110 °C.

Melt-quenched coordination polymer glass shows exclusive H⁺ conductivity (8.0 × 10⁻³ S cm⁻¹ at 120 °C, anhydrous) and optimal mechanical properties (42.8 Pa s at 120 °C), enables the operation of an all-solid-state proton battery from RT to 110 °C.     

A general method for site-selective Csp3–S bond formation via cooperative catalysis

Herein, we report a copper-catalysed site-selective thiolation of Csp³–H bonds of aliphatic amines. The method features a broad substrate scope and good functional group compatibility. Primary, secondary, and tertiary C–H bonds can be converted into C–S bonds with a high efficiency. The late-stage modification of biologically active compounds by this method was also demonstrated. Furthermore, the one-pot preparation of pyrrolidine or piperidine compounds via a domino process was achieved.

A copper-catalyzed site-selective thiolation of Csp³–H bonds of aliphatic amines was developed. The method features a broad substrate scope and good functional group tolerance.     

Reversible cooperative dihydrogen binding and transfer with a bis-phosphenium complex of chromium

The reversible reaction of H₂ with a bis-phosphenium complex of chromium provides a rare example of 3d transition metal/phosphenium cooperativity. Photolysis induces the activation of H₂ and yields a spectroscopically detectable phosphenium-stabilized (σ–H₂)-complex, readily showing exchange with gaseous H₂ and D₂. Further reaction of this complex affords a phosphine-functionalized metal hydride, representing a unique example of reversible H₂ cleavage across a 3d M P bond. The same species is also accessible via stepwise H⁺/H⁻ transfer to the bis-phosphenium complex, and releases H₂ upon heating or irradiation. Dihydrogen transfer from the H₂-complex to styrene is exploited to demonstrate the first example of promoting hydrogenation with a phosphenium complex.

Photolysis of a phosphenium complex enables reversible activation of H₂ to yield a dihydrogen complex which stimulates H₂ cleavage or catalytic hydrogenation.     

Ortho-aryl substituted DPEphos ligands: rhodium complexes featuring C–H anagostic interactions and B–H agostic bonds

The synthesis of new Schrock–Osborn Rh(i) pre-catalysts with ortho-substituted DPEphos ligands, [Rh(DPEphos-R)(NBD)][BAr^F₄] [R = Me, OMe, ⁱPr; Ar^F = 3,5-(CF₃)₂C₆H₃], is described. Along with the previously reported R = H variant, variable temperature ¹H NMR spectroscopic and single-crystal X-ray diffraction studies show that these all have axial (C–H)⋯Rh anagostic interactions relative to the d⁸ pseudo square planar metal centres, that also result in corresponding downfield chemical shifts. Analysis by NBO, QTAIM and NCI methods shows these to be only very weak C–H⋯Rh bonding interactions, the magnitudes of which do not correlate with the observed chemical shifts. Instead, as informed by Scherer''s approach, it is the topological positioning of the C–H bond with regard to the metal centre that is important. For [Rh(DPEphos–ⁱPr)(NBD)][BAr^F₄] addition of H₂ results in a Rh(iii) ⁱPr–C–H activated product, [Rh(κ³,σ-P,O,P-DPEphos-ⁱPr′)(H)][BAr^F₄]. This undergoes H/D exchange with D₂ at the ⁱPr groups, reacts with CO or NBD to return Rh(i) products, and reaction with H₃B·NMe₃/tert-butylethene results in a dehydrogenative borylation to form a complex that shows both a non-classical B–H⋯Rh 3c-2e agostic bond and a C–H⋯Rh anagostic interaction at the same metal centre.

Rh(i) complexes of ortho-substituted DPEphos-R (R = H, Me, OMe, ⁱPr) ligands show anagostic interactions; for R =ⁱPr C–H activation/dehydrogenative borylation forms a product exhibiting both B–H/Rh 3c-2e agostic and C–H/Rh anagostic motifs.     

Asymmetric synthesis of primary amines catalyzed by thermotolerant fungal reductive aminases

Chiral primary amines are important intermediates in the synthesis of pharmaceutical compounds. Fungal reductive aminases (RedAms) are NADPH-dependent dehydrogenases that catalyse reductive amination of a range of ketones with short-chain primary amines supplied in an equimolar ratio to give corresponding secondary amines. Herein we describe structural and biochemical characterisation as well as synthetic applications of two RedAms from Neosartorya spp. (NfRedAm and NfisRedAm) that display a distinctive activity amongst fungal RedAms, namely a superior ability to use ammonia as the amine partner. Using these enzymes, we demonstrate the synthesis of a broad range of primary amines, with conversions up to >97% and excellent enantiomeric excess. Temperature dependent studies showed that these homologues also possess greater thermal stability compared to other enzymes within this family. Their synthetic applicability is further demonstrated by the production of several primary and secondary amines with turnover numbers (TN) up to 14 000 as well as continous flow reactions, obtaining chiral amines such as (R)-2-aminohexane in space time yields up to 8.1 g L⁻¹ h⁻¹. The remarkable features of NfRedAm and NfisRedAm highlight their potential for wider synthetic application as well as expanding the biocatalytic toolbox available for chiral amine synthesis.

Fungal reductive aminases as effective biocatalysts for the preparation of chiral primary amines.     

Biosynthesis of the catalytic H-cluster of [FeFe] hydrogenase: the roles of the Fe–S maturase proteins HydE,HydF, and HydG

[FeFe] hydrogenases carry out the redox interconversion of protons and molecular hydrogen (2H⁺ + 2e⁻ ⇌ H₂) at a complex Fe–S active site known as the H-cluster. The H-cluster consists of a [4Fe–4S] subcluster, denoted here as [4Fe]_H, linked via a cysteine sulfur to an interesting organometallic [2Fe]_H subcluster thought to be the subsite where the catalysis occurs. This [2Fe]_H subcluster consists of two Fe atoms, linked with a bridging CO and a bridging SCH₂NHCH₂S azadithiolate (adt), with additional terminal CO and CN ligands bound to each Fe. Synthesizing such a complex organometallic unit is a fascinating problem in biochemistry, complicated by the toxic nature of both the CO and CN⁻ species and the relative fragility of the azadithiolate bridge. It has been known for a number of years that this complex biosynthesis is carried out by a set of three essential Fe–S proteins, HydE, HydF, and HydG. HydF is a GTPase, while HydE and HydG are both members of the large family of radical S-adenosylmethionine (rSAM) enzymes. In this perspective we describe the history of research and discovery concerning these three Fe–S “maturase” proteins and describe recent evidence for a sequential biosynthetic pathway beginning with the synthesis of a mononuclear organometallic [Fe(ii)(CO)₂CN(cysteine)] complex by the rSAM enzyme HydG and its subsequent activation by the second rSAM enzyme HydE to form a highly reactive Fe(i)(CO)₂(CN)S species. In our model a pair of these Fe(i)(CO)₂(CN)S units condense to form the [Fe(CO)₂(CN)S]₂ diamond core of the [2Fe]_H cluster, requiring only the installation of the central CH₂NHCH₂ portion of the azadithiolate bridge, whose atoms are all sourced from the amino acid serine. This final step likely occurs with an interplay of HydE and HydF, the details of which yet remain to be elucidated.

Fe–S cluster enzymes HydG, HydE, and HydF provide sequential assembly of the catalytic H-cluster of [FeFe] hydrogenase.     

In situ K-edge X-ray absorption spectroscopy of the ligand environment of single-site Au/C catalysts during acetylene hydrochlorination

The replacement of HgCl₂/C with Au/C as a catalyst for acetylene hydrochlorination represents a significant reduction in the environmental impact of this industrial process. Under reaction conditions atomically dispersed cationic Au species are the catalytic active site, representing a large-scale application of heterogeneous single-site catalysts. While the metal nuclearity and oxidation state under operating conditions has been investigated in catalysts prepared from aqua regia and thiosulphate, limited studies have focused on the ligand environment surrounding the metal centre. We now report K-edge soft X-ray absorption spectroscopy of the Cl and S ligand species used to stabilise these isolated cationic Au centres in the harsh reaction conditions. We demonstrate the presence of three distinct Cl species in the materials; inorganic Cl⁻, Au–Cl, and C–Cl and how these species evolve during reaction. Direct evidence of Au–S interactions is confirmed in catalysts prepared using thiosulfate precursors which show high stability towards reduction to inactive metal nanoparticles. This stability was clear during gas switching experiments, where exposure to C₂H₂ alone did not dramatically alter the Au electronic structure and consequently did not deactivate the thiosulfate catalyst.

In situ chlorine and sulphur XAS shows a dynamic ligand environment around cationic Au single-sites during acetylene hydrochlorination.     

Time-resolved luminescence detection of peroxynitrite using a reactivity-based lanthanide probe

Peroxynitrite (ONOO⁻) is a powerful and short-lived oxidant formed in vivo, which can react with most biomolecules directly. To fully understand the roles of ONOO⁻ in cell biology, improved methods for the selective detection and real-time analysis of ONOO⁻ are needed. We present a water-soluble, luminescent europium(iii) probe for the rapid and sensitive detection of peroxynitrite in human serum, living cells and biological matrices. We have utilised the long luminescence lifetime of the probe to measure ONOO⁻ in a time-resolved manner, effectively avoiding the influence of autofluorescence in biological samples. To demonstrate the utility of the Eu(iii) probe, we monitored the production of ONOO⁻ in different cell lines, following treatment with a cold atmospheric plasma device commonly used in the clinic for skin wound treatment.

Reactivity-based europium(iii) probe displays excellent selectivity for peroxynitrite (ONOO⁻), enabling its time-resolved luminescence detection in living cells.     

Single-atom nickel terminating sp2 and sp3 nitride in polymeric carbon nitride for visible-light photocatalytic overall water splitting

Polymeric carbon nitride (PCN) has been widely used as a metal-free photocatalyst for solar hydrogen generation from water. However, rapid charge carrier recombination and sluggish water catalysis kinetics have greatly limited its photocatalytic performance for overall water splitting. Herein, a single-atom Ni terminating agent was introduced to coordinate with the heptazine units of PCN to create new hybrid orbitals. Both theoretical calculation and experimental evidence revealed that the new hybrid orbitals synergistically broadened visible light absorption via a metal-to-ligand charge transfer (MLCT) process, and accelerated the separation and transfer of photoexcited electrons and holes. The obtained single-atom Ni terminated PCN (PCNNi), without an additional cocatalyst loading, realized efficient photocatalytic overall water splitting into easily-separated gas-product H₂ and liquid-product H₂O₂ under visible light, with evolution rates reaching 26.6 and 24.0 μmol g⁻¹ h⁻¹, respectively. It was indicated that single-atom Ni and the neighboring C atom served as water oxidation and reduction active sites, respectively, for overall water splitting via a two-electron reaction pathway.

Single-atom Ni terminating agent is introduced to coordinate with sp² or sp³ N atoms in the heptazine units of PCN, realizing visible-light photocatalytic overall water splitting to H₂O₂ and H₂ without additional cocatalyst.     

Nickel-catalyzed C–O/N–H,C–S/N–H,and C–CN/N–H annulation of aromatic amides with alkynes: C–O,C–S,and C–CN activation

The Ni-catalyzed reaction of ortho-phenoxy-substituted aromatic amides with alkynes in the presence of LiO^tBu as a base results in C–O/N–H annulation with the formation of 1(2H)-isoquinolinones. The use of a base is essential for the reaction to proceed. The reaction proceeds, even in the absence of a ligand, and under mild reaction conditions (40 °C). An electron-donating group on the aromatic ring facilitates the reaction. The reaction was also applicable to carbamate (C–O bond activation), methylthio (C–S bond activation), and cyano (C–CN bond activation) groups as leaving groups.

The Ni-catalyzed reaction of ortho-phenoxy-substituted aromatic amides with alkynes in the presence of LiO^tBu as a base results in C–O/N–H annulation with the formation of 1(2H)-isoquinolinones.     

Single-molecule fluorescence detection of a tricyclic nucleoside analogue

Fluorescent nucleobase surrogates capable of Watson–Crick hydrogen bonding are essential probes of nucleic acid structure and dynamics, but their limited brightness and short absorption and emission wavelengths have rendered them unsuitable for single-molecule detection. Aiming to improve on these properties, we designed a new tricyclic pyrimidine nucleoside analogue with a push–pull conjugated system and synthesized it in seven sequential steps. The resulting C-linked 8-(diethylamino)benzo[b][1,8]naphthyridin-2(1H)-one nucleoside, which we name ABN, exhibits ε₄₄₂ = 20 000 M⁻¹ cm⁻¹ and Φ_em,540 = 0.39 in water, increasing to Φ_em = 0.50–0.53 when base paired with adenine in duplex DNA oligonucleotides. Single-molecule fluorescence measurements of ABN using both one-photon and two-photon excitation demonstrate its excellent photostability and indicate that the nucleoside is present to > 95% in a bright state with count rates of at least 15 kHz per molecule. This new fluorescent nucleobase analogue, which, in duplex DNA, is the brightest and most red-shifted known, is the first to offer robust and accessible single-molecule fluorescence detection capabilities.

Fluorescent nucleoside analogue ABN is readily detected at the single-molecule level and retains a quantum yield >50% in duplex DNA oligonucleotides.     

Transition-metal-mediated reduction and reversible double-cyclization of cyanuric triazide to an asymmetric bitetrazolate involving cleavage of the six-membered aromatic ring

Cyanuric triazide reacts with several transition metal precursors, extruding one equivalent of N₂ and reducing the putative diazidotriazeneylnitrene species by two electrons, which rearranges to N-(1′H-[1,5′-bitetrazol]-5-yl)methanediiminate (biTzI²⁻) dianionic ligand, which ligates the metal and dimerizes, and is isolated from pyridine as [M(biTzI)]₂Py₆ (M = Mn, Fe, Zn, Cu, Ni). Reagent scope, product analysis, and quantum chemical calculations were combined to elucidate the mechanism of formation as a two-electron reduction preceding ligand rearrangement.

Cyanuric triazide reacts with transition metal precursors, extruding N₂ and reducing the ligand by two electrons, which breaks an aromatic ring and rearranges to a bitetrazolylmethanediiminate (biTzI²⁻) ligand, forming two new aromatic rings.     

Carbon monoxide and hydrogen (syngas) as a C1-building block for selective catalytic methylation

A catalytic reaction using syngas (CO/H₂) as feedstock for the selective β-methylation of alcohols was developed whereby carbon monoxide acts as a C1 source and hydrogen gas as a reducing agent. The overall transformation occurs through an intricate network of metal-catalyzed and base-mediated reactions. The molecular complex [Mn(CO)₂Br[HN(C₂H₄PⁱPr₂)₂]] 1 comprising earth-abundant manganese acts as the metal component in the catalytic system enabling the generation of formaldehyde from syngas in a synthetically useful reaction. This new syngas conversion opens pathways to install methyl branches at sp³ carbon centers utilizing renewable feedstocks and energy for the synthesis of biologically active compounds, fine chemicals, and advanced biofuels.

A broadly applicable catalytic process for the selective β-methylation of alcohols is presented using syngas (CO/H₂) directly as a C1 building block and the shown manganese complex in the presence of a base as the catalytic system.     

Effects of ruthenium hydride species on primary amine synthesis by direct amination of alcohols over a heterogeneous Ru catalyst

Heterogeneously catalysed synthesis of primary amines by direct amination of alcohols with ammonia has long been an elusive goal. In contrast to reported Ru-based catalytic systems, we report that Ru–MgO/TiO₂ acts as an effective heterogeneous catalyst for the direct amination of a variety of alcohols to primary amines at low temperatures of ca. 100 °C without the introduction of H₂ gas. The present system could be applied to a variety of alcohols and provides an efficient synthetic route for 2,5-bis(aminomethyl)furan (BAMF), an attention-getting biomonomer. The high catalytic performance can be rationalized by the reactivity tuning of Ru–H species using MgO. Spectroscopic measurements suggest that MgO enhances the reactivity of hydride species by electron donation from MgO to Ru.

Ru–MgO/TiO₂ exhibited high catalytic performance for direct amination of alcohols based on the acceleration effects of MgO.     

Coordination polymer glass from a protic ionic liquid: proton conductivity and mechanical properties as an electrolyte

High proton conducting electrolytes with mechanical moldability are a key material for energy devices. We propose an approach for creating a coordination polymer (CP) glass from a protic ionic liquid for a solid-state anhydrous proton conductor. A protic ionic liquid (dema)(H₂PO₄), with components which also act as bridging ligands, was applied to construct a CP glass (dema)_0.35[Zn(H₂PO₄)_2.35(H₃PO₄)_0.65]. The structural analysis revealed that large Zn–H₂PO₄⁻/H₃PO₄ coordination networks formed in the CP glass. The network formation results in enhancement of the properties of proton conductivity and viscoelasticity. High anhydrous proton conductivity (σ = 13.3 mS cm⁻¹ at 120 °C) and a high transport number of the proton (0.94) were achieved by the coordination networks. A fuel cell with this CP glass membrane exhibits a high open-circuit voltage and power density (0.15 W cm⁻²) under dry conditions at 120 °C due to the conducting properties and mechanical properties of the CP glass.

A proton-conducting coordination polymer glass derived from a protic ionic liquid works as a moldable solid electrolyte and the anhydrous fuel cell showed I–V performance of 0.15 W cm⁻² at 120 °C.     

Modulation of the superficial electronic structure via metal–support interaction for H2 evolution over Pd catalysts

Electronic interactions can radically enhance the performance of supported metal catalysts and are critical for fundamentally understanding the nature of catalysts. However, at the microscopic level, the details of such interactions tuning the electronic properties of the sites on the metal particle''s surface and metal–support interface remain obscure. Herein, we found polarized electronic metal–support interaction (pEMSI) in oxide-supported Pd nanoparticles (NPs) describing the enhanced accumulation of electrons at the surface of NPs (superficial Pd^δ−) with positive Pd atoms distributed on the interface (interfacial Pd^δ+). More superficial Pd^δ− species mean stronger pEMSI resulting from the synergistic effect of moderate Pd–oxide interaction, high structural fluxionality and electron transport activity of Pd NPs. The surface Pd^δ− species are responsible for improved catalytic performance for H₂ evolution from metal hydrides and formates. These extensive insights into the nature of supported-metal NPs may open new avenues for regulating a metal particle''s electronic structure precisely and exploiting high-performance catalysts.

A new type of electronic effect, polarized metal-support interaction (pEMSI), in oxide-supported Pd nanoparticles describing the enhanced accumulation of electrons at the superficial surface is responsible for improved catalytic H₂ evolution.     

Acid–base chemistry at the single ion limit

We present the results of acid–base experiments performed at the single ion (H⁺ or OH⁻) limit in ∼6 aL volume nanopores incorporating electrochemical zero-mode waveguides (E-ZMWs). At pH 3 each E-ZMW nanopore contains ca. 3600H⁺ ions, and application of a negative electrochemical potential to the gold working electrode/optical cladding layer reduces H⁺ to H₂, thereby depleting H⁺ and increasing the local pH within the nanopore. The change in pH was quantified by tracking the intensity of fluorescein, a pH-responsive fluorophore whose intensity increases with pH. This behavior was translated to the single ion limit by changing the initial pH of the electrolyte solution to pH 6, at which the average pore occupancy 〈n〉_pore ∼3.6H⁺/nanopore. Application of an electrochemical potential sufficiently negative to change the local pH to pH 7 reduces the proton nanopore occupancy to 〈n〉_pore ∼0.36H⁺/nanopore, demonstrating that the approach is sensitive to single H⁺ manipulations, as evidenced by clear potential-dependent changes in fluorescein emission intensity. In addition, at high overpotential, the observed fluorescence intensity exceeded the value predicted from the fluorescence intensity-pH calibration, an observation attributed to the nucleation of H₂ nanobubbles as confirmed both by calculations and the behavior of non-pH responsive Alexa 488 fluorophore. Apart from enhancing fundamental understanding, the approach described here opens the door to applications requiring ultrasensitive ion sensing, based on the optical detection of H⁺ population at the single ion limit.

Visualizing dynamic change in the number of protons during electroreduction of protons in attoliter volume zero-mode waveguides.     

Nitric oxide monooxygenation (NOM) reaction of cobalt-nitrosyl {Co(NO)}8 to CoII-nitrito {CoII(NO2−)}: base induced hydrogen gas (H2) evolution

Here, we report the nitric oxide monooxygenation (NOM) reactions of a Co^III-nitrosyl complex (1, {Co-NO}⁸) in the presence of mono-oxygen reactive species, i.e., a base (OH⁻, tetrabutylammonium hydroxide (TBAOH) or NaOH/15-crown-5), an oxide (O²⁻ or Na₂O/15-crown-5) and water (H₂O). The reaction of 1 with OH⁻ produces a Co^II-nitrito complex {3, (Co^II-NO₂⁻)} and hydrogen gas (H₂), via the formation of a putative N-bound Co-nitrous acid intermediate (2, {Co-NOOH}⁺). The homolytic cleavage of the O–H bond of proposed [Co-NOOH]⁺ releases H₂via a presumed Co^III-H intermediate. In another reaction, 1 generates Co^II-NO₂⁻ when reacted with O²⁻via an expected Co^I-nitro (4) intermediate. However, complex 1 is found to be unreactive towards H₂O. Mechanistic investigations using ¹⁵N-labeled-¹⁵NO and ²H-labeled-NaO²H (NaOD) evidently revealed that the N-atom in Co^II-NO₂⁻ and the H-atom in H₂ gas are derived from the nitrosyl ligand and OH⁻ moiety, respectively.

Base-induced hydrogen (H₂) gas evolution in the nitric oxide monoxygenation reaction.

As a radical species, nitric oxide (NO) has attracted great interest from the scientific community due to its major role in various physiological processes such as neurotransmission, vascular regulation, platelet disaggregation and immune responses to multiple infections.¹ Nitric oxide synthase (NOS),² and nitrite reductase (NiR)³ enzymes are involved in the biosynthesis of NO. NOSs produce NO by the oxidation of the guanidine nitrogen in l-arginine.⁴ However, in mammals and bacteria, NO₂⁻ is reduced to NO by NiRs in the presence of protons, i.e., NO₂⁻ + e⁻ + 2H⁺ → NO + H₂O.⁵ Biological dysfunctions may cause overproduction of NO, and being radical it leads to the generation of reactive nitrogen species (RNS), i.e., peroxynitrite (PN, OONO⁻)⁶ and nitrogen dioxide (˙NO₂),⁷ upon reaction with reactive oxygen species (ROS) such as superoxide (O₂˙⁻),⁸ peroxide (H₂O₂),⁹ and dioxygen (O₂).¹⁰ Hence, it is essential to maintain an optimal level of NO. In this regard, nitric oxide dioxygenases (NODs)¹¹ are available in bio-systems to convert excess NO to biologically benign nitrate (NO₃⁻).¹²NO₂⁻ + Fe^II + H⁺ ↔ NO + Fe^III + OH⁻1[M–NO]ⁿ + 2OH⁻ → [M–NO₂]⁽ⁿ⁻²⁾ + H₂O2NOD enzymes generate NO₃⁻ from NO;^11b,12−13 however, the formation of NO₂⁻ from NO is still under investigation. Clarkson and Bosolo reported NO₂⁻ formation in the reaction of Co^III-NO and O₂.¹⁴ Nam and co-workers showed the generation of Co^II-NO₂⁻ from Co^III-NO upon reaction with O₂˙⁻.¹⁵ Recently, Mondal and co-workers reported NO₂⁻ formation in the reaction of Co^II-NO with O₂.¹⁶ Apart from cobalt, the formation of Cu^II-NO₂⁻ was also observed in the reaction of Cu^I-NO and O₂.¹⁷ For metal-dioxygen adducts, i.e., Cr^III-O₂˙⁻ and Mn^IV-O₂²⁻, NOD reactions led to the generation of Cr^III-NO₂⁻ (ref. 18) and Mn^V O + NO₂⁻,¹⁹ respectively. However, the NOD reaction of Fe^III-O₂˙⁻ and Fe^III-O₂²⁻ with NO and NO⁺, respectively, generated Fe^III-NO₃⁻via Fe^IV O and ˙NO₂.²⁰ Ford suggested that the reaction of ferric-heme nitrosyl with hydroxide leads to the formation of NO₂⁻ and H⁺.¹² Lehnert and co-workers reported heme-based Fe-nitrosyl complexes²¹ showing different chemistries due to the Fe^II-NO⁺ type electronic structures. On the other hand, Bryan proposed that the one-electron reduction of NO₂⁻ to NO in ferrous heme protein is reversible (eqn (1)).²² Also, it is proposed that excess NO in biological systems is converted to NO₂⁻ and produces one equivalent of H⁺ upon reaction with ˙OH.²³ Previously reported reactivity of M–NOs of Fe²⁴ with OH⁻ suggested the formation of NO₂⁻ and one equivalent of H⁺, where H⁺ further reacts with one equivalent of OH⁻ and produces H₂O (eqn (2)).²⁵Here in this report, we explore the mechanistic aspects of nitric oxide monooxygenation (NOM) reactions of the Co^III-nitrosyl complex, [(12TMC)Co^III(NO⁻)]²⁺/{Co(NO)}⁸ (1),^15,26 bearing the 12TMC ligand (12TMC = 1,4,7,10-tetramethyl-1,4,7,10-tetraazacyclododecane) with mono-oxygen reactive species (O²⁻, OH⁻ and H₂O) (Scheme 1). Complex 1 reacts with the base (OH⁻, tetrabutylammonium hydroxide (TBAOH)/or NaOH in the presence of 15-crown-5 as the OH⁻ source) and generates the corresponding Co^II-nitrito complex, [(12TMC)Co^II(NO₂⁻)]⁺ (3), with the evolution of hydrogen gas (H₂) via the formation of a plausible N-bound Co-nitrous acid intermediate ([Co-NOOH]⁺, 2) in CH₃CN at 273 K (Scheme 1, reaction (I)). Also, when 1 reacts with the oxide (O²⁻ or Na₂O in the presence of 15-crown-5), it generates the Co^II-nitrito complex (3) via a probable Co^I-nitro, [(12TMC)Co^I(NO₂⁻)] (4), intermediate (Scheme 1, reaction (II)); however, 1 does not react with water (Scheme 1, reaction (III)). Mechanistic investigations using ¹⁵N-labeled-¹⁵NO, D-labeled-NaOD and ¹⁸O-labelled-¹⁸OH⁻ demonstrated, unambiguously, that the N and O-atoms in the NO₂⁻ ligand of 3 resulted from NO and OH⁻ moieties; however, the H-atoms of H₂ are derived from OH⁻. To the extent of our knowledge, the present work reports the very first systematic study of Co^III-nitrosyl complex reactions with H₂O, OH⁻ and O²⁻. This new finding presents an alternative route for NO₂⁻ generation in biosystems, and also illustrates a new pathway of H₂ evolution, in addition to the reported literature.^12,27Open in a separate windowScheme 1Nitric oxide monooxygenation (NOM) reactions of cobalt-nitrosyl complex (1) in the presence of a base (OH⁻), sodium oxide (Na₂O) and water (H₂O).To further explore the chemistry of [(12TMC)Co^III(NO⁻)]²⁺ (1),^15,26 and the mechanistic insights of NOM reactions, we have reacted it with a base (OH⁻), an oxide (O²⁻), and water (H₂O). When complex 1 was reacted with TBAOH in CH₃CN, the color of complex 1 changed to light pink from dark pink. In this reaction, the characteristic absorption band of 1 (370 nm) disappears within 2 minutes (Fig. 1a; ESI, Experimental section (ES) and Fig. S1a^†), producing a Co^II-nitrito complex, [(12TMC)Co^II(NO₂⁻)]⁺ (3), with H₂ (Scheme 1, reaction (Ib)), in contrast to the previous reports on base induced NOM reactions (eqn (2)).^12,25,28 The spectral titration data confirmed that the ratio-metric equivalent of OH⁻ to 1 was 1 : 1 (ESI, Fig. S1b^†). 3 was determined to be [(12TMC)Co^II(NO₂⁻)](BF₄) based on various spectroscopic and structural characterization experiments (vide infra).^15,26bOpen in a separate windowFig. 1(a) UV-vis spectral changes of 1 (0.50 mM, black line) upon addition of OH⁻ (1 equiv.) in CH₃CN under Ar at 273 K. Black line (1) changed to red line (3) upon addition of OH⁻. Inset: IR spectra of 3-¹⁴NO₂⁻ (blue line) and 3-¹⁵NO₂⁻ (red line) in KBr. (b) ESI-MS spectra of 3. The peak at 333.2 is assigned to [(12TMC)Co^II(NO₂)]⁺ (calcd m/z 333.1). Inset: isotopic distribution pattern for 3-¹⁴NO₂⁻ (red line) and 3-¹⁵NO₂⁻ (blue line).The FT-IR spectrum of 3 showed a characteristic peak for nitrite stretching at 1271 cm⁻¹ (Co^II-14NO₂⁻) and shifted to 1245 cm⁻¹ (Co^II-15NO₂⁻) when 3 was prepared by reacting ¹⁵N-labeled NO (Co^III-15NO) with OH⁻ (Inset, Fig. 1a and Fig. S2^†). The shifting of NO₂⁻ stretching (Δ = 30 cm⁻¹) indicates that the N-atom in the NO₂⁻ ligand is derived from Co^III-15NO. The ESI-MS spectrum of 3 showed a prominent peak at m/z 333.2, [(12TMC)Co^II(¹⁴NO₂⁻)]⁺ (calcd m/z 333.2), which shifted to 334.2, [(12TMC)Co^II(¹⁵NO₂⁻)]⁺ (calcd m/z 334.2), when the reaction was performed with Co^III-15NO (Inset, Fig. 1b; ESI, Fig. S3a^†); indicating clearly that NO₂⁻ in 3 was derived from the NO moiety of 1. In addition, we have reacted 1 with Na¹⁸OH (ES and ESI^†), in order to follow the source of the second O-atom in 3-NO₂⁻. The ESI-MS spectrum of the reaction mixture, obtained by reacting 1 with Na¹⁸OH, showed a prominent peak at m/z 335.2, [(12TMC)Co^II(¹⁸ONO⁻)]⁺ (calcd m/z 335.2), (SI, Fig. S3b^†) indicating clearly that NO₂⁻ in 3 was derived from ¹⁸OH⁻. The ¹H NMR spectrum of 3 did not show any signal for aliphatic protons of the 12TMC ligand, suggesting a bivalent cobalt center (Fig. S4^†).^26b Furthermore, we have determined the magnetic moment of 3, using Evans'' method, and it was found to be 4.62 BM, suggesting a high spin Co(ii) metal center with three unpaired electrons (ESI^† and ES).²⁹ The exact conformation of 3 was provided by single-crystal X-ray crystallographic analysis (Fig. 2b, ESI, ES, Fig. S5, and Tables T1 and T2^†) and similar to that of previously reported Co^II-NO₂⁻/M^II-NO₂⁻.^15,26b Also, we have quantified the amount of nitrite (90 ± 5%), formed in the above reaction, using the Griess reagent (ESI, ES, and Fig. S6^†).Open in a separate windowFig. 2Displacement ellipsoid plot (20% probability) of 3 at 100 K. Disordered C-atoms of the TMC ring, anion and H-atoms have been removed for clarity.As is known from the literature, a metal-nitrous acid intermediate may form either by the reaction of a metal-nitrosyl with a base²⁷ or by the metal-nitrite reaction with an acid (nitrite reduction chemistry);^26b however, the products of both the reactions are different. Here, for the first time, we have explored the reaction of Co^III-nitrosyl (1) with a base. In this reaction, it is clear that the formation of Co^II-nitrito would be accomplished by the release of H₂ gas via the generation of a transient N-bound [Co-(NOOH)]⁺ intermediate (Scheme 2, reaction (II)). The formation of Co^II-NO₂⁻ (3) from the [Co-(NOOH)]⁺ intermediate is likely to proceed by either (i) homolytic cleavage of the O–H bond and release of H₂via the proposed Co^III-H transient species (Co^III-H = Co^II + 1/2H₂)³⁰ (Scheme 2, reaction (III)), as reported in previous literature where the reduced cobalt, in a number of different ligand environments, is a good H⁺ reduction catalyst and generates H₂ gas via a Co^III-H intermediate³¹ or (ii) heterolytic cleavage of the O–H bond and the formation of Co^I-NO₂⁻ + H⁺.²⁷ In the present study, we observed the formation of 3 and H₂via the plausible homolytic cleavage of the NOO–H moiety of 2 as shown in Scheme 2, in contrast to the previous reports on base-induced reactions on metal-nitrosyls (eqn (3)).²⁷ Taking together both possibilities, (i) is the most reasonable pathway for the NOM reaction of complex 1 in the presence of a base (as shown in Scheme 2, reaction (III)). And the reaction is believed to go through a Co^III-H intermediate as reported previously in Co^I-induced H⁺ reduction in different ligand frameworks and based on literature precedence, we believe that complex 1 acts in a similar manner.³¹Open in a separate windowScheme 2NOM reaction of complex 1 in the presence of OH⁻, showing the generation of Co^II-nitrito (3) and H₂via a Co(iii)-hydrido intermediate.In contrast to an O-bound Co^II-ONOH intermediate, where N–O bond homolysis of the ON-OH moiety generates H₂O₂ (Scheme 2, reaction (IV)),^26b the N-bound [Co-(NOOH)]⁺ intermediate decomposes to form NO₂⁻ and a Co(iii)-H transient species, arising from β-hydrogen transfer from the NOO–H moiety to the cobalt-center (Scheme 2, reaction (II)).^30a,c,32 The Co(iii)-hydrido species may generate H₂ gas either (a) by its transformation to the Co(ii)-nitrito complex (2) and H₂ gas as observed in the case of Co^III-H intermediate chemistry^30a,c,e−g as proposed in the chemistry of the Co^I complex with H⁺ reduction³¹ and other metal-hydrido intermediates³² and also explained in O₂ formation in PN chemistry^17,33 or (b) by the reacting with another [Co-(NOOH)]⁺ intermediate (Scheme 2, reaction (III)).Furthermore, we have confirmed the H₂ formation in the NOM reaction of 1 with OH⁻ by headspace gas mass spectrometry (Fig. 3a). Also, carrying out the reaction of 1 with NaOD leads to the formation of the [Co-(NOOD)]⁺ intermediate, which then transforms to a Co^III-D transient species. Further, as described above, the Co^III-D species releases D₂ gas, detected by headspace gas mass spectrometry (Fig. 3b), which evidently established that H₂ gas formed in the reaction of 1 with OH⁻. In this regard, we have proposed that in the first step of this reaction, the nucleophilic addition of OH⁻ to {Co-NO}⁸ generates a transient N-bound [Co-(NOOH)]⁺ intermediate that is generated by an internal electron transfer to Co^III (Scheme 2, reaction (I)). By following the mechanism proposed in the case of Co^III-H,^30a−c O₂,¹⁵ and H₂O₂(ref. 26b) formation, we have proposed the sequences of the NOM reaction of 1, which leads to the generation of Co^II-nitrito and H₂ (Scheme 2, reaction (I)–(III) and Scheme 3). In the second step, O–H bond homolytic cleavage generates a Co^III-H transient species + NO₂⁻via a β-hydrogen elimination reaction of the [Co-(NOOH)]⁺ intermediate.³² The Co^III-H intermediate may undergo the following reactions to generate H₂ gas and Co^II-nitrito either (a) by the natural decomposition of the Co^III-H transient species to generate H₂,^30a,c,e−g or (b) by the H-atom abstraction from another [Co-(NOOH)]⁺ intermediate (Scheme 3). Also, to validate our assumption that the reaction goes through a plausible N-bound [Co-(NOOH)]⁺ intermediate followed by its transformation to the Co^III-H species (vide supra), we have performed the reaction of 1 with NaOH/NaOD (in 1 : 1 ratio). In this reaction, we have observed the formation of a mixture of H₂, D₂, and HD gases, which indicates clearly that the reaction goes through the formation of Co^III-H and Co^III-D transient species via the aforementioned mechanism (Fig. 3c). This is the only example where tracking of the H atoms has confirmed the H₂ generation from an N-bound NOO–H moiety as proposed for H₂ formation from Co^III-H.³⁰Open in a separate windowFig. 3Mass spectra of formation of (a) H₂ in the reaction of 1 (5.0 mM) with NaOH (5.0 mM), (b) D₂ in the reaction of 1 (5.0 mM) with NaOD (5.0 mM), (c) D₂, HD, and H₂ in the reaction of 1 (5.0 mM) with NaOD/NaOH (1 : 1), and (d) H₂ in the reaction of 1 (5.0 mM) with NaOH in the presence of 2,4 DTBP (50 mM).Open in a separate windowScheme 3NOM reaction of complex 1 in the presence of OH⁻, showing the different steps of the reaction.While, we do not have direct spectral evidence to support the formation of the transient N-bound [Co-(NOOH)]⁺ intermediate and its decomposition to the Co^III-H transient species via β-hydrogen transfer from the NOOH moiety to the cobalt center, support for its formation comes from our finding that the reactive hydrogen species can be trapped by using 2,4-di-tert-butyl-phenol (2,4-DTBP).³⁴ In this reaction, we observed the formation of 2,4-DTBP-dimer (2,4-DTBP-D, ∼67%) as a single product (ESI, ES, and Fig. S7^†). This result can readily be explained by the H-atom abstraction reaction of 2,4-DTBP either by [Co-(NOOH)]⁺ or Co^III-H, hence generating a phenoxyl-radical and 3 with H₂ (Fig. 3d and Scheme 2, reaction (a)). Also, we have detected H₂ gas formation in this reaction (ESI,^† ES, and Fig. 3d). In the next step, two phenoxyl radicals dimerized to give 2,4-DTBP-dimer (Scheme 2c, reaction (II)). Thus, the observation of 2,4-DTBP-dimer in good yield supports the proposed reaction mechanism (Scheme 2, reaction (a) and (b)). Further, the formation of 2,4 DTBP as a single product also rules out the formation of the hydroxyl radical as observed in the case of an O-bound nitrous acid intermediate.^26bFurthermore, we have explored the NOM reactivity of 1 with Na₂O/15-crown-5 (as the O²⁻ source) and observed the formation of the Co^II-nitrito complex (3) via a plausible Co^I-nitro (4) intermediate (Scheme 1, reaction (IIa); also see the ESI^† and ES); however, 1 was found to be inert towards H₂O (Scheme 1, reaction (III); also see the ESI, ES and Fig. S8^†). The product obtained in the reaction of 1 with O²⁻ was characterized by various spectroscopic measurements.^15,26b The UV-vis absorption band of 1 (λ_max = 370 nm) disappears upon the addition of 1 equiv. of Na₂O and a new band (λ_max = 535 nm) forms, which corresponds to 3 (ESI, Fig. S9^†). The FT-IR spectrum of the isolated product of the above reaction shows a characteristic peak for Co^II-bound nitrite at 1271 cm⁻¹, which shifts to 1245 cm⁻¹ when exchanged with ¹⁵N-labeled-NO (¹⁵N¹⁶O) (ESI, ES, and Fig. S10^†), clearly indicating the generation of nitrite from the NO ligand of complex 1.^26b The ESI-MS spectrum recorded for the isolated product (vide supra) shows a prominent ion peak at m/z 333.1, and its mass and isotope distribution pattern matches with [(12-TMC)Co^II(NO₂)]⁺ (calc. m/z 333.1) (ESI, Fig. S11^†). Also, we quantified the amount of 3 (85 ± 5%) by quantifying the amount of nitrite (85 ± 5%) using the Griess reagent test (ESI, ES, and Fig. S6^†).In summary, we have demonstrated the reaction of Co^III-nitrosyl, [(12-TMC)Co^III(NO⁻)]²⁺/{CoNO}⁸ (1), with mono-oxygen reactive species (O²⁻, OH⁻ and H₂O) (Scheme 1). For the first time, we have established the clear formation of a Co^II-nitrito complex, [(12TMC)Co^II(NO₂⁻)]⁺ (3), and H₂ in the reaction of 1 with one equivalent of OH⁻via a transient N-bound [Co-(NOOH)]⁺ (2) intermediate. This [Co-(NOOH)]⁺ intermediate undergoes the O–H bond homolytic cleavage and generates a Co^III-H transient species with NO₂⁻, via a β-hydrogen elimination reaction of the [Co-(NOOH)]⁺ intermediate, which upon decomposition produces H₂ gas. This is in contrast to our previous report, where acid-induced nitrite reduction of 3 generated 1 and H₂O₂via an O-bound Co^II-ONOH intermediate.^26b Complex 1 was found to be inert towards H₂O; however, we have observed the formation of 3 when reacted with O²⁻. It is important to note that H₂ formation involves a distinctive pathway of O–H bond homolytic cleavage in the [Co-(NOOH)]⁺ intermediate, followed by the generation of the proposed Co^III-H transient species (Co^II + 1/2H₂)³⁰ prior to H₂ evolution as described in Co^I chemistry with H⁺ in many different ligand frameworks.³¹ The present study is the first-ever report where the base induced NOM reaction of Co^III-nitrosyl (1) leads to Co^II-nitrito (3) with H₂ evolution via an N-bound [Co-(NOOH)]⁺ intermediate, in contrast to the chemistry of O-bound Co^II-ONOH^26b, hence adding an entirely new mechanistic insight of base induced H₂ gas evolution and an additional pathway for NOM reactions.     

Boosting homogeneous chemoselective hydrogenation of olefins mediated by a bis(silylenyl)terphenyl-nickel(0) pre-catalyst

The isolable chelating bis(N-heterocyclic silylenyl)-substituted terphenyl ligand [Si^II(Terp)Si^II] as well as its bis(phosphine) analogue [P^III(Terp)P^III] have been synthesised and fully characterised. Their reaction with Ni(cod)₂ (cod = cycloocta-1,5-diene) affords the corresponding 16 VE nickel(0) complexes with an intramolecular η²-arene coordination of Ni, [E(Terp)E]Ni(η²-arene) (E = P^III, Si^II; arene = phenylene spacer). Due to a strong cooperativity of the Si and Ni sites in H₂ activation and H atom transfer, [Si^II(Terp)Si^II]Ni(η²-arene) mediates very effectively and chemoselectively the homogeneously catalysed hydrogenation of olefins bearing functional groups at 1 bar H₂ pressure and room temperature; in contrast, the bis(phosphine) analogous complex shows only poor activity. Catalytic and stoichiometric experiments revealed the important role of the η²-coordination of the Ni(0) site by the intramolecular phenylene with respect to the hydrogenation activity of [Si^II(Terp)Si^II]Ni(η²-arene). The mechanism has been established by kinetic measurements, including kinetic isotope effect (KIE) and Hammet-plot correlation. With this system, the currently highest performance of a homogeneous nickel-based hydrogenation catalyst of olefins (TON = 9800, TOF = 6800 h⁻¹) could be realised.

The isolable chelating bis(N-heterocyclic silylenyl)-substituted terphenyl ligand [Si^II(Terp)Si^II] as well as its bis(phosphine) analogue [P^III(Terp)P^III] have been synthesised and fully characterised.