Catalytic Transfer Hydrogenation Research Articles

Isopropanol/Water Bi‐Solvent Enhanced the Catalytic Transfer Hydrogenation of Levulinic Acid to γ‐Valerolactone over Ru‐PC Catalyst

AbstractCatalytic transfer hydrogenation of levulinic acid (LA) to γ‐valerolactone (GVL) was attractive in biomass conversions since GVL is highly useful in different applications, such as polymer synthesis, fuel, and food. Various catalytic systems were reported for the reaction, yet harsh reaction conditions were generally required, which could restrict the scaling up of the reaction. Herein, we developed an effective and green bi‐solvent system of isopropanol/water for the catalytic transfer hydrogenation of LA to GVL over a ruthenium–phosphorous carbon (Ru‐PC) catalyst. It was found that the presence of water in the solvent system promoted the production of GVL from LA. The effect of isopropanol/water ratios and other reaction conditions were investigated, exhibiting that 93.8% yield of GVL was achieved using isopropanol/water ratio of 2.5:2.5 at 140 °C for 4 h and over Ru‐PC catalyst. Combining water and organic solvent not only reduced the usage of organic solvent but also created an effective bi‐solvent system for catalytic reactions.

The Role of Frustrated Lewis Pair in Catalytic Transfer Hydrogenation of Furfural using Nickel Single-Atom Catalysts: A Theoretical Study.

The burgeoning field of frustrated Lewis pair (FLP) heterogeneous catalysts has garnered significant interest in recent years, primarily due to their inherent ability to activate H-source molecules, such as H2, thereby facilitating hydrogenation reactions. However, the application of single metal atom catalysts incorporating FLP sites has been relatively under-explored. In this study, non-precious transition metal atoms were anchored onto a C2N framework with an intrinsic cavity and a defective N-C sheet. Theoretical calculations substantiated energy barriers as low as 0.10 eV for isopropanol activation, thereby positioning these catalysts as highly promising candidates for catalytic transfer hydrogenation of furfural. Electronic structure analyses revealed that the H-O bond breakage in isopropanol molecules was significantly facilitated by the presence of FLP sites within the catalysts. Notably, both Ni-C2N and Ni-N6-C demonstrated exceptional potential as selective catalysts for the hydrogenation of furfural into furfuryl alcohol, exhibiting remarkably low barriers of only 0.65-0.72 eV for the rate-determining steps, which are notably lower than those observed in many traditional catalysts. Theoretical investigations strongly imply that the construction of single atom catalysts with FLP sites could significantly enhance the activity and selectivity for hydrogenation reactions, thus stimulating the experimental synthesis of such catalysts.

Optimization and reaction kinetics of catalytic transfer hydrogenation of 5‐hydroxymethylfurfural to 2, 5‐dimethylfuran over CuCoOx catalysts

Optimization and reaction kinetics of catalytic transfer hydrogenation of 5‐hydroxymethylfurfural to 2, 5‐dimethylfuran over CuCoOx catalysts

Enantioselective Transfer Hydrogenation of α-Methoxyimino-β-keto Esters.

α-Methoxyimino-β-keto esters are reported to undergo highly enantioselective catalytic transfer hydrogenation using the Noyori-Ikariya complex RuCl(p-cymene)[(S,S)-Ts-DPEN] in a mixture of formic acid-triethylamine and dimethylformamide at 25 °C. The experimental study performed on over 25 substrates combined with computational analysis revealed that a Z-configured methoxyimino group positioned alpha to a ketone carbonyl leads to higher reactivity and mostly excellent enantioselectivity within this substrate class. Density functional theory calculations of competing transition states were used in rationalizing the origins of enantioselectivity and the possible role of the methoxyimino group in the reaction outcome.

Lignin-MOF hybrid polymetallic composites for selective hydrogenolysis of cellulose derived 5-hydroxymethylfurfural

The development of green, effective and inexpensive catalysts was important for the catalytic transfer hydrogenation of 5-hydroxymethylfurfural (HMF) to prepare 5-methylfurfuryl alcohol (MFA). The assembly of sodium lignosulfonate (LS) with NiCo-MOFs through a simple hydrothermal method was reported, and a series of iron-containing polymetallic hybrid catalysts were investigated. The introduction of iron led to the increase of medium strong acid sites and Lewis acid sites in the catalyst and enhanced the adsorption of furan rings, thus improved the catalytic activity. The effects of calcination temperature, iron content, and reaction parameters (including reaction temperature, pressure, hydrogen donor solvent) were all studied in detail. It was found that HMF could be completely converted over Fe@Ni3Co-MOF-LS, with a MFA yield of 88.75 % under the optimal condition (240 ℃, 2 MPa N2 in 4 h) without the presence of hydrogen. This study provided a new perspective for the utilization of lignin resource as carbon-based catalysts for the production of biomass-derived platform chemicals.

Ruthenium-p-Cymene Complexes Incorporating Substituted Pyridine–Quinoline Ligands with –Br (Br-Qpy) and –Phenoxy (OH-Ph-Qpy) Groups for Cytotoxicity and Catalytic Transfer Hydrogenation Studies: Synthesis and Characterization

Organometallic ruthenium complexes with p-cymene = 1-methyl-4-(1-methylethyl)-benzene and N^N = bidentate polypyridyl ligands constitute interesting candidates with biological and catalytic properties. Towards this aim, we have synthesized four ruthenium(II)–arene complexes of the type [Ru(η6-p-cymene)(N^N)Cl][X] (N^N = Br-Qpy = 6-bromo-4-phenyl-2-pyridin-2-yl-quinoline, X = Cl− (1a); PF6− (1b); N^N = OH-Ph-Qpy = 4-(4-phenyl-2-(pyridin-2-yl)quinolin-6-yl)phenol, X = Cl− (2a); PF6− (2b)). This is the first report of ruthenium(II) p-cymene complexes incorporating substituted pyridine–quinoline ligands, with –Br and –C6H4OH groups in the 6-position of quinoline. We also refer to the cytotoxicity of the ligands and their possible effect of modulating the activity of the ruthenium(II) complexes. These were characterized by a combination of spectroscopic methods (ATR-IR, UV–Vis, multinuclear NMR), elemental analysis, and conductivity measurements. The solid-state structure of 2b, determined by single-crystal X-ray diffraction, reveals a three-legged piano-stool geometry. The in vitro cytotoxic activities of the new complexes were evaluated in HEK293T (human embryonic kidney cells) and in HeLa cells (cervical cancer cells), via the MTT assay. Poor in vitro anticancer activities were observed for the HeLa cancer cell line, with 2a being the most potent (IC50 = 75 μΜ). The cytotoxicity of Br-Qpy in HEK293T is comparable to that of cisplatin. Both complexes 1a and 1b successfully catalyze the transfer hydrogenation of benzophenone to benzhydrol by 2-propanol at 82 °C. The catalytic performance of 1a in the ratio of S:Cat:B = 400:1:40 (S = substrate, Cat = catalyst, B = base = KOiPr) leads to a conversion of 94%, within 3 h of reaction. Presumably, catalytic transformation takes place via ruthenium(II) hydride species being the active catalyst.

Catalytic Transfer Hydrogenation of Carbonyls by SILP-Supported Manganese Nanoparticles

Catalytic Transfer Hydrogenation of Carbonyls by SILP-Supported Manganese Nanoparticles

Computational Exploration on Coupling Formic Acid Production with Propylene Synthesis via Catalytic Transfer Hydrogenation: The Role of CO2 beyond Reverse Water Gas Shift Reaction.

CO2-assisted propane dehydrogenation (CO2-ODHP) is emerging as an alternative route to the direct dehydrogenation of propane. Previous studies on CO2-ODHP have shown that the role of CO2 is to shift the reaction equilibrium toward the product side by consuming the produced H2 molecules via reverse water gas shift (RWGS) reaction. Since the ultimate fate of CO2 is to get reduced, we herein propose another pathway of CO2 reduction in the realm of CO2-ODHP─CO2 hydrogenation to formic acid (FA). With the objective of investigating the feasibility of this process, we, for the first time, carry out a computational investigation on coupling propane dehydrogenation with CO2 hydrogenation using a Ti-alkoxide-functionalized UiO-67 metal-organic framework. Analysis using the distortion/interaction model confirms that CO2 hydrogenation to FA is a preferred pathway over the RWGS reaction and hence can be realized in practice. Our study also highlights the importance of intersystem crossing, which provides an opportunity to access nonground state potential energy surfaces while undergoing chemical transformations. Again, subsequent addition of water molecules has shown to ease product desorption by 41 kcal/mol. Our study, therefore, hints at an unexplored role of CO2 beyond the RWGS reaction in oxidative propane dehydrogenation.

(Invited) Thermal and Plasmon-Mediated Catalytic Transfer Hydrogenation Reactions on Nanostructured Metal Surfaces

Catalytic hydrogenation reactions play crucial roles in fine chemical production and pharmaceutical synthesis. Compared to direct hydrogenation of organic compounds with pressurized hydrogen gas, catalytic transfer hydrogenation reactions using inexpensive and readily accessible small molecules as hydrogen-donors has been considered as a more versatile, scalable, and sustainable pathway toward enhanced chemoselectivity under mild reaction conditions. Noble metal nanoparticles, especially those within the sub-5 nm size regime, can efficiently catalyze the dehydrogenation of a series of hydrogen-storing molecules, such as ammonia borane, hydrazine, formaldehyde, formic acid, and isopropanol, to produce surface-adsorbed hydrogen species that actively hydrogenate a variety of organic substrate molecules. The transfer hydrogenation/hydrogenolysis reactions are mechanistically complex, and may occur selectively along multiple distinct pathways, exhibiting kinetic features signifying the Langmuir–Hinshelwood, Eley–Rideal, autocatalysis, and reversible reaction mechanisms, respectively, depending on the compositions of the metal catalysts and the chemical nature of the hydrogen donors. In this talk, I will share with the audience some new insights concerning the detailed mechanisms of transfer hydrogenation reactions over metal nanocatalyst surfaces. We employ surface-enhanced Raman scattering (SERS) as an in situ fingerprinting spectroscopic tool to precisely resolve the detailed structural evolution of molecular adsorbates during catalytic reactions, based upon which the key intermediates along different reaction pathways are unambiguously identified. The results of deliberately designed in situ SERS measurements show that the chemoselective transfer hydrogenation of nitrophenyl isocyanide by ammonia borane may proceed on noble metal nanocatalyst surfaces selectively through either a unimolecular or a bimolecular pathway, depending on how the nitrophenyl isocyanide adsorbates interact with the metal nanoparticle surfaces. The experimental observations are corroborated by density functional theory calculations, which shed light on the underlying relationships between catalyst-adsorbate interactions and reaction pathway selection. We have further demonstrated that the photoexcited plasmonic hot carriers in the metal nanoparticles can be effectively harnessed to fine-regulate the activation energy barriers associated with the rate-limiting steps for the transfer hydrogenation of nitrophenyl isocyanide on Pd nanocatalyst surfaces when ammonium formate serves as the hydrogen donor. Our results clearly demonstrate the feasibility of using plasmonic hot carriers to kinetically modulate catalytic molecule-transforming processes.

Cobalt-Catalyzed Chemo- and Stereoselective Transfer Semihydrogenation of 1,3-Dienes with Water as a Hydrogen Source.

(Z)-1,2-Disubstituted, trisubstituted, and tetrasubstituted alkenes are not only important units in medicinal chemistry, natural product synthesis, and material science but also useful intermediates in organic synthesis. Development of catalytic stereoselective transformations to access multisubstituted alkenes with various substitution patterns from easily accessible modular starting materials and readily available catalysts is a crucial goal in the field of catalysis. Water is an ideal hydrogen source for catalytic transfer hydrogenation despite of the high difficulty to activate water. Here, we report a cobalt-catalyzed protocol for regio- and stereoselective transfer semihydrogenation of 1,3-dienes to construct a broad scope of (Z)-1,2-disubstituted, (Z)-, (E)-trisubstituted, and tetrasubstituted alkenes in high stereoselectivity with H2O as the hydrogen source. Mechanistic studies revealed that the reactions proceeded through a unique Co(I)/Co(III) cycle and involved a 1,4-cobalt shift process, which is an unprecedented reaction pathway, providing a new platform for modular synthesis of multisubstituted alkenes as well as opportunities for designing novel reaction modes and pushing forward the advancement in organocobalt chemistry.

Facile generation of unsaturated-coordinated and atomically-dispersed hafnium active sites for the highly efficient catalytic transfer hydrogenation of levulinic acid

The sluggish kinetic of the hydrogen transfer reaction pose a significant challenge in developing efficient catalytic transfer hydrogenation (CTH) system for upgrading biomass-derived platform molecules. In this contribution, for the first time, hafnium (Hf) species have been found to coordinate with the hydroxyl groups on halloysite nanotubes surface to construct a single-atom Hf catalyst (Hf@HNTs) with unsaturated-coordinated structure at room temperature. Especially, the Hf(1.7)@HNTs delivered an impressive catalytic performance for the CTH of levulinic acid (LvA) to gamma-valerolactone (GVL) with high turn-over frequency (TOF) of 43.1 h−1 at 160 °C, considerably exceeding that of coordination-saturated HfO2 and state-of-art Hf-based catalysts. Experimental and density functional theory (DFT) studies revealed that Hf(1.7)@HNTs possessed unsaturated-coordinated and atomically-dispersed Hf-O Lewis acid-base pairs, which favored the adsorption and activation of LvA. Moreover, DFT calculations explicitly demonstrated that the energy barriers for the hydrogen transfer between the LvA and hydrogen donor were significantly reduced on the Hf(1.7)@HNTs than that of HfO2.

Pd-Catalyzed Transfer Hydrogenation of Alkenes Using Tetrahydroxydiboron as the Sole Hydrogen Donor

AbstractTetrahydroxydiboron-mediated catalytic transfer hydrogenations have typically involved co-additives that, like tetrahydroxydiboron itself, are H atom donors. Herein we report an alkene transfer hydrogenation method with tetrahydroxydiboron as the sole source of H atoms. The reaction uses Pd(OAc)2 as a convenient putative colloid pre-catalyst, and cyclic monoethers are competent solvents. Highly efficient alkene deuteration is demonstrated using tetradeuteroxydiboron.

Enhanced catalytic transfer hydrogenation of biomass-based furfural into furfuryl alcohol over Co3O4-based mixed oxide catalysts from hydrotalcite

Catalytic furfural (FF) into high value-added furfuryl alcohol (FOL) is a very important biomass improvement process and remains a challenging task. Herein, a series of Co-based composite oxide (CoMgAl-LDO) catalysts with highly dispersed Co3O4-based spinel oxide nanoparticles were synthesized by the topological transformation of Co-based ternary layered hydroxides (CoMgAl-LDH) under calcination conditions and tested for catalytic transfer hydrogenation of FF to FOL using isopropanol (2-PrOH) as hydrogen donor. The CoMgAl-LDO, especially Co1.5Mg1.5Al1-LDO calcinated at 500 °C (Co1.5Mg1.5Al1-LDO-500) offered the outstanding catalytic performance for the catalytic transfer hydrogenation of FF to FOL (99.7 % FF conversion and 95.9 % FOL selectivity), which was attributed to effectively dispersed active sites, abundant acid-base sites and mesoporous structure. Additionally, the Co1.5Mg1.5Al1-LDO-500 catalyst manifested good stability with wider universality to other carbonyl compounds, making the catalytic system extremely economical and practical in various biomass hydrogenation processes.

Lignin-tailored fabrication of Ni single atom catalyst with Ni-N3 active site for efficient and selective catalytic transfer hydrogenation of lignin-derived aldehydes

Developing sustainable catalytic processes for catalytic transfer hydrogenation (CTHDO) of lignin-derived aldehydes to renewable fuels and chemicals is essential for scale valorization of vast underused lignin. Herein, the work contributes to the efficient and selective vanillin (VAN) CTHDO process using formic acid (FA) as the H-donor over a novel lignin-coordinated N-anchoring Ni single-atom catalyst (Ni SAs-N@LC). Ni SAs-N@LC was fabricated through facile pyrolysis of lignin-Ni/Zn complex mixed with melamine, in which lignin localized the Ni atoms through its negatively charged groups (e.g. phenolic OH) and the dispersed Ni atoms were further anchored by the N-doped carbon support to form Ni-N3 active structure. DFT calculations revealed that the Ni-N3 structure preferentially adsorbed the –CHO end of VAN and endowed the catalyst with superior hydrogen evolution capacity. Therefore, Ni SAs-N@LC exhibited outstanding catalytic performance (98.93% of VAN conversion and 97.3% of 2-methoxy-4-methylphenol selectivity) which was significantly higher than two reference catalysts Ni NPs@LC (without N-anchoring) and Ni@C (without lignin coordination and N-anchoring) as well as the previously reported Ni-based catalysts. Moreover, Ni SAs-N@LC presented excellent feasibility to the CTHDO of a wide range of lignin-derived aldehydes and exhibited superior cycling durability in FA system owing to its acid resistance property. Consequently, this work provides a facile preparation method for atomically dispersed biomass-based catalysts and further demonstrates its favorable applicability in the CTHDO of lignin-derived aldehydes.

Effect of Support Functionalization on Catalytic Direct Hydrogenation and Catalytic Transfer Hydrogenation of Muconic Acid to Adipic Acid

The liquid-phase hydrogenation of muconic acid (MA) to produce bio-adipic acid (AdA) is a prominent environmentally friendly chemical process, that can be achieved through two distinct methodologies: catalytic direct hydrogenation using molecular hydrogen (H2), or catalytic transfer hydrogenation utilizing a hydrogen donor. In this study, both approaches were explored, with formic acid (FA) selected as the hydrogen source for the latter method. Palladium-based catalysts were chosen for these processes. Metal’s nanoparticles (NPs) were supported on high-temperature heat-treated carbon nanofibers (HHT-CNFs) due to their known ability to enhance the stability of this metal catalyst. To assess the impact of support functionalization on catalyst stability, the HHT-CNFs were further functionalized with phosphorus and oxygen to obtain HHT-P and HHT-O, respectively. In the hydrogenation reaction, catalysts supported on functionalized supports exhibited higher catalytic activity and stability compared to Pd/HHT, reaching an AdA yield of about 80% in less than 2 h in batch reactor. The hydrogen-transfer process also yielded promising results, particularly with the 1%Pd/HHT-P catalyst. This work highlights the efficacy of support functionalization in improving catalyst performance, particularly when formic acid is used as a safer and more cost-effective hydrogen donor in the hydrogen-transfer process.

Iridium(III) complexes with cyclometalated imidazolylidene ligands: sp2 phenyl C[sbnd]H activation vs sp2 benzyl C[sbnd]H activation and catalytic transfer hydrogenation reactions

Cyclometalated N-heterocyclic carbene (NHC) complexes possess fascinating electronic and catalytic properties. A series of cyclometalated iridium(III) complexes have been synthesized from the corresponding imidazolium salts via the aryl sp2 CH bond activation at the N1-phenyl/N3-benzyl wingtips of the imidazolylidene moiety. The electronic tuning towards the competitive formation of cyclometalated complexes (sp2 phenyl CH activation vs sp2 benzyl CH activation) has been discussed. These complexes have been utilized for the transfer hydrogenation (TH) reaction of 4-bromobenzaldehyde and 4-bromoacetophenone. These complexes showed excellent yields of the aryl-alcohols from 4-bromobenzaldehyde or 4-bromoacetophenone.

Synthesis and antibacterial activity of angular tetrahydrocycloamino [1,2-a]quinoxalin-4-one derivatives

ObjectivesThe resistance of bacteria to current antibiotics is a significant concern in treating infectious diseases, posing a strong threat to global health, food security, and development. This underscores the need for synthesizing new heterocyclic compounds as potential lead candidates in drug discovery. Quinoxalinone derivatives, known for their presence in various therapeutic agents and clinical drugs, are of particular interest. This study aimed to synthesize angular tricyclic tetrahydrocycloamino [1,2-a]quinoxalin-4-one derivatives and evaluate their antibacterial activities. Methods/analysisThe synthesis began with preparing precursors through the condensation of substituted 1-halogeno-2-nitrobenzene and cyclic amino acids in the presence of a base in ethanol, forming 2-nitrophenyl pyrrolidine/piperidine-2-carboxylic acids (acid adducts) 3a-3j. These acid adducts were then converted to amino esters 4a-4e by reacting them with thionyl chloride/ trimethylchlorosilane and methanol. Intramolecular reductive cyclization of the acid adducts or esters produced tetrahydrocycloamino [1,2-a]quinoxalin-4-ones (5a-5j) through catalytic hydrogen transfer hydrogenation. The chemical structures of the synthesized compounds were confirmed using FTIR, 1H and 13C NMR, MS, and CHN analysis. Their in vitro antibacterial activities were evaluated against ten bacterial strains using the broth microdilution method, revealing moderate to excellent activities compared to standard antibiotics streptomycin (STM) and nalidixic acid (NLD). FindingsCompound 5g demonstrated significant antibacterial activity (MIC = 15.6 μg/mL) against S. epidermidis, and compound 5c exhibited activity (MIC = 31.3 μg/mL) against S. aureus, both compared to STM and NLD. The results suggest that some of these compounds with promising antibacterial activity could serve as leads for discovering new antibacterial drugs. Novelty/improvementThe tetrahydrocycloamino [1,2-a]quinoxalin-4-ones were prepared using two methods with higher yields than previously reported, with the second method being novel for synthesizing quinoxalin-4-ones. The in vitro antibacterial studies of these compounds were reported, and substituted quinoxalin-4-ones were synthesized from N’-ethyl-N-(2-nitrophenyl)pyrrolidine-2-carboxamide 7 in good yield.

Low-Temperature Catalytic Transfer Hydrogenation of Biomass-Derived Furfural over Irreversibly Adsorbed and Highly Dispersed Zr(IV) Species.

Developing pure inorganic catalysts for low-energy transfer hydrogenation of biomass-derived furfural and alcohols below 100 °C is still challenging. This work reports highly dispersed Zr(IV) species catalysts prepared by irreversible adsorption of different solvent-dissolved Zr(IV) cations such as Zr4+ or [Zr4(OH)8(H2O)16]8+ on/in SBA-15 through Zr-O coordination, without adding an alkaline precipitant and calcination treatment. In the transfer hydrogenation of furfural to furfuryl alcohol, the Zr(IV) species catalysts exhibited unexpectedly outstanding transfer hydrogenation activity at low temperatures of 70 and 85 °C, superior to other transition-metal (Zr4+, Hf4+, Fe3+, etc.)- and main-group metal (Al3+, etc.)-based inorganic catalysts, which need high reaction temperatures above 100 °C, and comparable to the best-performing metal-organic hybrid catalysts with precise defect engineering modification or specific macromolecular ligands, and had negligible Zr leaching amounts (<0.01%) in water and in the collected liquid reaction medium from 7 cycles of reactions. In addition, the large strong Lewis acidic site amount rather than the large total acidic amount is a crucial condition for the catalysts to obtain high transfer hydrogenation activity, and basic sites were also involved in catalysis, and their absence would induce the acetalization side reaction. Furthermore, the catalysts were universal for low-temperature transfer hydrogenation of other aldehydes.

The Mechanism of Guerbet Reaction by Metal Ligand Cooperation Catalyst Mn-PCP.

The Guerbet reaction is important for the synthesis of longer-chain monoalcohols like isobutanol through catalytic transfer hydrogenation from short-chain methanol and ethanol. However, the mechanism becomes complicated, especially considering the variations in the different metal-ligand cooperation (MLC) catalysts used. In order to further understand the Guerbet reaction, DFT studies were performed to figure out the detailed mechanism initiated by the unique Mn-PCP MLC Catalyst. Our results suggest that even with the assistance of the carbanion site of the PCP ligand, the direct substitution mechanism is less favored than the condensation-reduction mechanism. The key step of the reaction is the final reduction of the carbonyl, in which the 1,4-reduction of the unsaturated aldehyde is prior to the 3,4-reduction or 1,2-reduction due to the stronger interaction between the catalyst and the substrate. It is found that the production of isobutanol is preferred over n-butanol because of the lower total free energy barrier and lower relative free energy of the product. Finally, by changing the electronic effect of the carbanion site of the catalyst, we found that the relation between the electronic effect and the highest free energy span was not monotonous and a point with optimal electronic effect exists numerically.

In-cell Catalysis by Tethered Organo-Osmium Complexes Generates Selectivity for Breast Cancer Cells.

Anticancer agents that exhibit catalytic mechanisms of action offer a unique multi-targeting strategy to overcome drug resistance. Nonetheless, many in-cell catalysts in development are hindered by deactivation by endogenous nucleophiles. We have synthesised a highly potent, stable Os-based 16-electron half-sandwich ('piano stool') catalyst by introducing a permanent covalent tether between the arene and chelated diamine ligand. This catalyst exhibits antiproliferative activity comparable to the clinical drug cisplatin towards triple-negative breast cancer cells and can overcome tamoxifen resistance. Speciation experiments revealed Os to be almost exclusively albumin-bound in the extracellular medium, while cellular accumulation studies identified an energy-dependent, protein-mediated Os accumulation pathway, consistent with albumin-mediated uptake. Importantly, the tethered Os complex was active for in-cell transfer hydrogenation catalysis, initiated by co-administration of a non-toxic dose of sodium formate as a source of hydride, indicating that the Os catalyst is delivered to the cytosol of cancer cells intact. The mechanism of action involves the generation of reactive oxygen species (ROS), thus exploiting the inherent redox vulnerability of cancer cells, accompanied by selectivity for cancerous cells over non-tumorigenic cells.