Osmium Complexes Research Articles

Quinone Reduction by Organo-Osmium Half-Sandwich Transfer Hydrogenation Catalysts

Organo-osmium(II) 16-electron complexes [OsII(η6-arene)(R-PhDPEN)] (where η6-arene = para-cymene or biphenyl) can catalyze the reduction of prochiral ketones to optically pure alcohols in the presence of a hydride source. Such complexes can achieve the conversion of pyruvate to unnatural d-lactate in cancer cells. To improve the catalytic performance of these osmium complexes, we have introduced electron-donor and electron-acceptor substituents (R) into the para (R1) or meta (R2) positions of the chiral R-phenyl-sulfonyl-diphenylethylenediamine (R-PhDPEN) ligands and explored the reduction of quinones, potential biological substrates, which play a major role in cellular electron transfer chains. We show that the series of [OsII(η6-arene)(R-PhDPEN)] derivatives exhibit high turnover frequencies, enantioselectivities (>92%), and conversions (>93%) for the asymmetric transfer hydrogenation (ATH) of acetophenone-derived substrates and reduce duroquinone and menadione to their di-alcohol derivatives. Modeling of the catalysis using density functional theory (DFT) calculations suggests a mechanism involving formic acid deprotonation assisted by the catalyst amine groups, phenyl-duroquinone stacking, hydride transfer to OsII, possible CO2 coordination, and tilting of the η6-arene ring, followed by hydride transfer to the quinone. These findings not only reveal subtle differences between Ru(II) and Os(II) catalysts, but also introduce potential biological applications.

Synthesis, structure and anticancer properties of new biotin- and morpholine-functionalized ruthenium and osmium half-sandwich complexes.

Ruthenium(Ru) and osmium(Os) complexes are of sustained interest in cancer research and may be alternative to platinum-based therapy. We detail here three new series of ruthenium and osmium complexes, supported by physico-chemical characterizations, including time-dependent density functional theory, a combined experimental and computational study on the aquation reactions and the nature of the metal-arene bond. Cytotoxic profiles were then evaluated on several cancer cell lines although with limited success. Further investigations were, however, performed on the most active series using a genetic approach based on RNA interference and highlighted a potential multi-target mechanism of action through topoisomerase II, mitotic spindle, HDAC and DNMT inhibition.

Synthesis, characterization, and biological applications of pyrazole moiety bearing osmium(IV) complexes

Osmium (IV) complexes with pyrazole nucleus containing ligands were synthesized. Os(IV) compounds were characterized using ESI-MS, ICP-OES, IR spectroscopy, electronic spectroscopy, conductance, and magnetic measurements. Whereas, ligands were characterized by heteronuclear spectroscopy, (1H and 13C), IR spectroscopy, and elemental analysis. All the compounds were tested for their potential to interact with HS-DNA by absorption titration, fluorescence spectroscopy, viscosity measurement, and docking study. The quenching constant and Stern Volmer constant values were calculated using fluorescence study. The synthesized compounds were studied for in-vitro bacteriostatic and cytotoxic activities. The cancer cell line studies of all the synthesized complexes were carried out on human lung cancer cells (A549). Supplemental data for this article is available online at https://doi.org/10.1080/15257770.2021.1921795 .

Reduction Mechanisms of Anticancer Osmium(VI) Complexes Revealed by Atomic Telemetry and Theoretical Calculations.

Resonant X-ray emission spectroscopy (RXES) has developed in the past decade as a powerful tool to probe the chemical state of a metal center and in situ study chemical reactions. We have used it to monitor spectral changes associated with the reduction of osmium(VI) nitrido complexes to the osmium(III) ammine state by the biologically relevant reducing agent, glutathione. RXES difference maps are consistent with the proposed DFT mechanism and the formation of two stable osmium(IV) intermediates, thereby supporting the overall pathway for the reduction of these high-valent anticancer metal complexes for which reduction by thiols within cells may be essential to the antiproliferative activity.

Emission Switching in the Near-Infrared by Reversible Trans-Cis Photoisomerization of Styrylbenzene-Conjugated Osmium Terpyridine Complexes.

A new array of homoleptic osmium(II) complexes based on styrylbenzene-conjugated terpyridine ligands (tpy-pvp-X) were synthesized and their photophysical, electrochemical, and photoisomerization behaviors thoroughly investigated in this work. Both electron-donating and -withdrawing substituents were incorporated onto a tpy-pvp-X (X = H, Me, Cl, NO2, and Ph) moiety to tune the optical properties and also the rate of photoisomerization behaviors in the complexes. All complexes display strong spin-allowed singlet metal-to-ligand charge-transfer bands in the visible (495-506 nm) and weak singlet ground state to triplet metal-to-ligand charge-transfer (3MLCT) broad bands within the 600-700 nm range. The complexes also exhibit strong phosphorescence emission from their 3MLCT state in the near-infrared domain (737-752 nm) at room temperature with excited-state lifetimes spanning between 107 and 165 ns. Two styrylbenzene units promote reversible trans-trans to trans-cis/cis-cis isomerization induced by light. The rate constants and quantum yields of photoisomerization were found to vary linearly with the Hammett σp parameters of the substituents. The rate and quantum yields were also found to decrease with increasing polarity of the solvents. Considerable modulation of the optical behavior along with luminescence switching in the complexes has been achieved upon photoisomerization. Moreover, the optical outputs as a function of two photonic stimuli inputs were used to demonstrate the binary function of a two-input IMPLICATION logic gate. In conjunction with the experimental study, computational investigations were also carried out in all three conformations of the complexes (trans-trans, trans-cis, and cis-cis) to have a perception of their electronic structures and for correct assignment of their absorption and emission spectral bands.

Cyclometalated Osmium Compounds and beyond: Synthesis, Properties, Applications.

The synthesis of cyclometalated osmium complexes is usually more complicated than of other transition metals such as Ni, Pd, Pt, Rh, where cyclometalation reactions readily occur via direct activation of C–H bonds. It differs also from their ruthenium analogs. Cyclometalation for osmium usually occurs under more severe conditions, in polar solvents, using specific precursors, stronger acids, or bases. Such requirements expand reaction mechanisms to electrophilic activation, transmetalation, and oxidative addition, often involving C–H bond activations. Osmacycles exhibit specific applications in homogeneous catalysis, photophysics, bioelectrocatalysis and are studied as anticancer agents. This review describes major synthetic pathways to osmacycles and related compounds and discusses their practical applications.

Osmium-arene complexes with high potency towards Mycobacterium tuberculosis.

The treatment of tuberculosis (TB) poses a major challenge as frontline therapeutic agents become increasingly ineffective with the emergence and spread of drug-resistant strains of Mycobacterium tuberculosis (Mtb). To combat this global health problem, new antitubercular agents with novel modes of action are needed. We have screened a close family of 17 organometallic half-sandwich Os(II) complexes [(arene)Os(phenyl-azo/imino-pyridine)(Cl/I)]+Y– containing various arenes (p-cymene, biphenyl, or terphenyl), and NMe2, F, Cl, or Br phenyl or pyridyl substituents, for activity towards Mtb in comparison with normal human lung cells (MRC5). In general, complexes with a monodentate iodido ligand were more potent than chlorido complexes, and the five most potent iodido complexes (MIC 1.25–2.5 µM) have an electron-donating Me2N or OH substituent on the phenyl ring. As expected, the counter anion Y (PF6–, Cl–, I–) had little effect on the activity. The pattern of potency of the complexes towards Mtb is similar to that towards human cells, perhaps because in both cases intracellular thiols are likely to be involved in their activation and their redox mechanism of action. The most active complex against Mtb is the p-cymene Os(II) NMe2-phenyl-azopyridine iodido complex (2), a relatively inert complex that also exhibits potent activity towards cancer cells. The uptake of Os from complex 2 by Mtb is rapid and peaks after 6 h, with temperature-dependence studies suggesting a major role for active transport. Significance to Metallomics Antimicrobial resistance is a global health problem. New advances are urgently needed in the discovery of new antibiotics with novel mechanisms of action. Half-sandwich organometallic complexes offer a versatile platform for drug design. We show that with an appropriate choice of the arene, an N,N-chelated ligand, and monodentate ligand, half-sandwich organo–osmium(II) complexes can exhibit potent activity towards Mycobacterium tuberculosis (Mtb), the leading cause of death from a single infectious agent. The patterns of activity of the 17 azo- and imino-pyridine complexes studied here towards Mtb and normal lung cells suggest a common redox mechanism of action involving intracellular thiols.

Amphiphilicity in Oxygen Atom Transfer Reactions of Oxobis(iminoxolene)osmium Complexes.

Oxobis(iminoxolene)osmium(VI) compounds (Rap)2OsO (Rap = 2-(4-RC6H4N)-4,6-tBu2C6H2O) are readily deoxygenated by phosphines and phosphites to give five-coordinate (Rap)2Os(PR'3) or six-coordinate (Rap)2Os(PR'3)2. Structural data indicate that this net two-electron reduction is accompanied by apparent oxidation of the iminoxolene ligands due to their greater ability to engage in π donation to the reduced deoxy form of the osmium complex. In (Rap)2Os(PR'3)2, the HOMO is a ligand-based combination of the iminoxolene redox-active orbitals, while the LUMO is a highly covalent metal-iminoxolene π* orbital. In the trans isomer, the HOMO is required to be ligand-localized by symmetry, while in the cis isomer, the ligands adopt a conformation that minimizes metal-ligand π* interactions in the HOMO. Kinetic studies indicate that the deoxygenations involve the rate-determining attack of the phosphorus(III) reagent on the five-coordinate oxo complexes. Varying the substituents of the aryl groups on the iminoxolene ligands or on the triarylphosphines has little effect on the rate of oxygen atom transfer, with the best correlation shown between oxygen atom transfer rates and the HOMO-LUMO gap of the oxo complexes. This suggests that the osmium oxo group shows a balance between electrophilic and nucleophilic character in its oxygen atom transfer reactions with phosphorus(III) reagents.

Electrochemical sensor for the assessment of carbohydrate deficient transferrin: Application to diagnosis of congenital disorders of glycosilation

Carbohydrate deficient transferrin (CDT) is used as biomarker of different health problems as, for example, congenital disorders of glycosylation (CDG). We propose a screen-printed-based electrochemical sensor for the determination of carbohydrate deficient transferrin using an Os (VI) tag-based electrochemistry. When transferrin is labeled with Os (VI) complex, it generates two voltammetric signals: one from carbohydrates (electrochemical signal of osmium (VI) complex at -0.9 V/Ag) and one from the amino acids present in glycoprotein (intrinsic electrochemical signal of glycoprotein at +0.8 V/Ag). The relationship between the two analytical signals (carbohydrate signal/protein signal) is an indicator of the degree of glycosylation (electrochemical index of glycosylation), which has shown an excellent correlation (r = 0.990) with the official parameter %CDT obtained by CE-UV. The suitability of this approach was demonstrated by analyzing serum samples from CDG patients.

A focused review on the unconventional alkyne activations by ruthenium(II) and osmium(II) complexes supported by 1,2-bis(diphenylphosphino)methane (dppm)

While the activation of alkynes by ruthenium(II) and osmium(II) bis-diphosphine complexes in the form of [RuII/OsII(P^P)2X2] has been studied for nearly three decades and are known to give a variety of metal−vinylidene, −allenylidene, and −alkynyl complexes, recent findings on the isolation of unprecedented organometallic complexes from alkynes and [RuII/OsII(P^P)2X2] suggest the existence of unconventional reaction pathways which have been largely overlooked. In this focused review, a brief overview on the conventional reactivities between alkynes and cis-[RuII/OsII(dppm)2Cl2] (dppm = 1,2-bis(diphenylphosphino)methane) will first be provided, which is then followed by discussions on the recent discoveries of the unconventional reactivities with emphasis on the mechanistic insights into the Ru/Os-induced alkyne transformations.

Single Platinum Atom Doping to Silver Clusters Enables Near‐Infrared‐to‐Blue Photon Upconversion

AbstractPhoton upconversion (UC) from near‐infrared (NIR) to visible has been realized using singlet‐to‐triplet absorption of sensitizers, which are currently limited to osmium complexes and semiconductor nanocrystals. Motivated by the atomically precise tunability of electronic structure and photophysical properties of noble metal clusters, which often possess absorption bands that extend into the NIR region, we investigated MAg24(SR)18 (M=Ag, Pt; SR=2,4‐dimethylbenzenethiolate) clusters as a new NIR‐absorbing sensitizer for triplet–triplet annihilation UC. Combined with a blue light emitter, the NIR excitation (λex=785 nm) of Ag25(SR)18 results in no UC emission, while PtAg24(SR)18 exhibits strong UC emission. This enhancement is primarily due to a significant increase in the intersystem crossing quantum yield of the cluster associated with the spin–orbit coupling enhancement in the M@Ag12 core.

Single Platinum Atom Doping to Silver Clusters Enables Near-Infrared-to-Blue Photon Upconversion.

Photon upconversion (UC) from near-infrared (NIR) to visible has been realized using singlet-to-triplet absorption of sensitizers, which are currently limited to osmium complexes and semiconductor nanocrystals. Motivated by the atomically precise tunability of electronic structure and photophysical properties of noble metal clusters, which often possess absorption bands that extend into the NIR region, we investigated MAg24 (SR)18 (M=Ag, Pt; SR=2,4-dimethylbenzenethiolate) clusters as a new NIR-absorbing sensitizer for triplet-triplet annihilation UC. Combined with a blue light emitter, the NIR excitation (λex =785 nm) of Ag25 (SR)18 results in no UC emission, while PtAg24 (SR)18 exhibits strong UC emission. This enhancement is primarily due to a significant increase in the intersystem crossing quantum yield of the cluster associated with the spin-orbit coupling enhancement in the M@Ag12 core.

Oxygen Atom Insertion into the Osmium–Carbon Bond via an Organometallic Oxido–Osmium(V) Intermediate

A cyclometalated osmium(III) complex, [OsIIICl(phpy)(tpy)]+ (OsIII(phpy); phpy = 2-C6H4-2′-C5H4N-κC,N) is synthesized from OsIIICl3(tpy) (tpy = 2,2′;6′,2″-terpyridine) and 2-phenylpyridine (H-phpy)...

Development of a panchromatic photosensitizer and its application to photocatalytic CO2 reduction.

We designed and synthesized a heteroleptic osmium(ii) complex with two different tridentate ligands, Os. Os can absorb the full wavelength range of visible light owing to S–T transitions, and this was supported by TD-DFT calculations. Excitation of Os using visible light of any wavelength generates the same lowest triplet metal-to-ligand charge-transfer excited state, the lifetime of which is relatively long (τem = 40 ns). Since excited Os could be reductively quenched by 1,3-dimethyl-2-(o-hydroxyphenyl)-2,3-dihydro-1H-benzo[d]imidazole, Os displays high potential as a panchromatic photosensitizer. Using a combination of Os and a ruthenium(ii) catalyst, CO2 was photocatalytically reduced to HCOOH via irradiation with 725 nm light, and the turnover number reached 81; irradiation with light at λex > 770 nm also photocatalytically induced HCOOH formation. These results clearly indicate that Os can function as a panchromatic redox photosensitizer.

Voltammetric sensing of glycans modified by osmium(VI)ligand complexes. The influence of N-acetyl neuraminic acid

A quick and simple way of glycan analysis is combining glycans modification by sixvalent osmium complexes with nitrogenous ligands, particularly with N,N,N´,N´-tetramethylethylenediamine (Os(VI)tem) and their voltammetric analysis. Os(VI)tem-modified oligosaccharides are reduced at the mercury electrode yielding peaks I-III, representing reduction steps of Os(VI) oxocomplexes. In this work we clarified the individual reduction steps and showed analytical applications for Os(VI)tem modified glycans, including distinguishing sialoglycan regioisomer type or discriminating glycans according to the sialic acid content. Presence or absence of sialic acid was tested in complex glycans as well as in glycoproteins.

Theoretical Studies of Photodynamic Therapy Properties of Azopyridine <i>δ</i>-OsCl<sub>2</sub>(Azpy)<sub>2</sub> Complex as a Photosensitizer by a TDDFT Method

Photochemical reactions have an important place in photodynamic treatments. A good use of this therapeutic method requires a good mastery of the mechanisms of the reactions involved. Therefore, we have explored in this work the photosensitization mechanism of an organometallic complex of azopyridine δ-OsCl2(Azpy)2 through a calculation with the method of Time Dependent Density Functional Theory TDDFT. First, we evaluated the effect of polar and non-polar solvents on the triplet and singlet excited states of this complex. Then secondly, we highlighted the photosensitization mechanism to understand how the complex acts over the diseased cells. These investigations have shown that the δ-OsCl2(Azpy)2 complex is likely to develop photodynamic activity according to two mechanisms: on one hand, it can generate damage to DNA bases or target tissues indirectly through the production of singlet oxygen in water and in DMSO. On the second hand, through the production of the anionic superoxide radical in water can act directly or indirectly on these substrates. In addition, polar solvents are assumed to better carry out the photochemical reactions of this azopyridine complex of osmium.

Computational Investigation of the Preferred Binding Modes of N2O in Group 8 Metal Complexes.

Nitrous oxide (N2O) is a potentially important oxidant for green chemistry applications but thus far has shown limited examples as a ligand for transition metal complexes. Given the lack of reported N2O complexes, density functional theory was utilized to study the potential binding effects in multiple group 8 metal complexes. N2O is found to be a very weakly π-accepting ligand (approximately 1/3 as effective as CO). With the weak π-accepting character, the N2O is predicted to be bound through the nitrogen atom in a linear geometry. In all calculated ruthenium and osmium complexes, the nitrogen bound mode of binding is preferred. Only by introduction of a very weak π-donor metal (such as iron) can the N2O be found to slightly prefer binding through the oxygen atom in a purely σ-donor fashion.

Osmium catalysis in the reductive amination using carbon monoxide as a reducing agent

A systematic study of the osmium-catalyzed reductive amination reaction using carbon monoxide as a reducing agent is presented. Seven cationic, anionic, and neutral osmium complexes with various ligands (including Cl−, arene, Cp*, CO, and pyridine) were synthesized and tested under different conditions. [(cymene)OsCl2]2 (0.5 %) in the presence of a silver salt was found to be optimal. Pleasingly, the developed methodology could be applied to aliphatic and aromatic aldehydes and ketones as well as primary and secondary amines allowing the preparation of various secondary and tertiary amines in good to excellent yields with an average TON of 77. The catalytic performance of the reaction was compared with that of previously reported iridium-, ruthenium-, and rhodium-catalyzed reactions, and the following trend was observed: Ir < Os < Ru < Rh. Moreover, a possible mechanism was proposed based on DFT studies and X-ray analysis.

Intracellular Photophysics of an Osmium Complex bearing an Oligothiophene Extended Ligand.

This contribution describes the excited‐state properties of an Osmium‐complex when taken up into human cells. The complex 1 [Os(bpy)2(IP‐4T)](PF6)2 with bpy=2,2′‐bipyridine and IP‐4T=2‐{5′‐[3′,4′‐diethyl‐(2,2′‐bithien‐5‐yl)]‐3,4‐diethyl‐2,2′‐bithiophene}imidazo[4,5‐f][1,10]phenanthroline) can be discussed as a candidate for photodynamic therapy in the biological red/NIR window. The complex is taken up by MCF7 cells and localizes rather homogeneously within in the cytoplasm. To detail the sub‐ns photophysics of 1, comparative transient absorption measurements were carried out in different solvents to derive a model of the photoinduced processes. Key to rationalize the excited‐state relaxation is a long‐lived 3ILCT state associated with the oligothiophene chain. This model was then tested with the complex internalized into MCF7 cells, since the intracellular environment has long been suspected to take big influence on the excited state properties. In our study of 1 in cells, we were able to show that, though the overall model remained the same, the excited‐state dynamics are affected strongly by the intracellular environment. Our study represents the first in depth correlation towards ex‐vivo and in vivo ultrafast spectroscopy for a possible photodrug.

Square and octahedral supramolecular assemblies of diosmium sawhorse complexes

The reaction between Os3(CO)12 and 2,6-naphthalenedicarboxylic acid (H2NDC) followed by reaction with tri-p-tolylphosphane produced the complex [Os2(CO)4(p-tolyl3P)2]4(μ4-NDCA)4 (1), which is the first example of a square octanuclear osmium complex. The reaction of Os3(CO)12 with benzene-1,3,5-tricarboxylic acid (H3BTC) yielded [Os2(CO)6]6(μ6-BTC)4 (2), which is the first octahedral dodecanuclear osmium complex. The basic metal building blocks in both 1 and 2 are Os2(CO)4L2 sawhorse units, which are linked together with di- or tricarboxylato spacers to form Os8 or Os12 supramolecules. The structures of these new MOF-like complexes were determined by X-ray crystallographic analysis.