The heterodinuclear dimetal decacarbonyl cation [MnFe(CO)10]+ has been synthesized by combining the metalloradical [Fe(CO)5]+⋅ with half an equivalent of Mn2(CO)10. The complex was subsequently isolated and characterized using single-crystal X-Ray Diffraction (scXRD), as well as IR, Raman, NMR and Mössbauer spectroscopy. Experimental results, complemented by DFT calculations of the relaxed force constants and an analysis of the electron density, reveal that the interaction between the two {M(CO)5} fragments in [MnFe(CO)10]+ is in between a covalent and a dative bond, representing a borderline case between the 2x17 VE and the 16+18 VE electron counting. Additionally, the known isoelectronic anion [CrMn(CO)10]- was prepared as its [PPN]+ salt and characterized for the first time by scXRD. These finding complete the series of structurally characterized isoelectronic dimetal decacarbonyls, spanning from [Cr2(CO)10]2- to [Fe2(CO)10]2+, the characteristics of all of which are compared based on experiment and theory.

The CO releasing ability of the complex [CpMo(CO)3Me] (1) (Cp = η5-C5H5) has been assessed using a deoxymyoglobin-carbonmonoxymyoglobin assay. In the dark, CO release was shown to be promoted by the reducing agent sodium dithionite in a concentration-dependent manner. At lower dithionite concentrations, where dithionite-induced CO release was minimised, irradiation at 365 nm with a low-power UV lamp resulted in a strongly enhanced release of CO (half-life (t1/2) = 6.3 min), thus establishing complex 1 as a photochemically activated CO-releasing molecule. To modify the CO release behaviour of the tricarbonyl complex, the possibility of obtaining inclusion complexes between 1 and β-cyclodextrin (βCD) or cucurbit[7]uril (CB7) by liquid-liquid interfacial precipitation (1@βCD(IP)), liquid antisolvent precipitation (1@CB7), and mechanochemical ball-milling (1@βCD(BM)) was evaluated. All these methods led to the isolation of a true inclusion compound (albeit mixed with nonincluded 1 for 1@βCD(BM)), as evidenced by powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), FT-IR and FT-Raman spectroscopies, and 13C{1H} magic angle spinning (MAS) NMR. PXRD showed that 1@βCD(IP) was microcrystalline with a channel-type crystal packing structure. High resolution mass spectrometry studies revealed the formation of aqueous phase 1 : 1 complexes between 1 and CB7. For 1@βCD(IP) and 1@CB7, the protective effects of the hosts led to a decrease in the CO release rates with respect to nonincluded 1. βCD had the strongest effect, with a ca. 10-fold increase in t1/4 for dithionite-induced CO release, and a ca. 2-fold increase in t1/2 for photoinduced CO release.

Carbon monoxide (CO) gas therapy has shown great potential as a very promising approach in the ongoing fight against tumors. However, delivering unstable CO to the tumor site and safely releasing it for maximum efficacy still have unsatisfactory outcomes. In this study, we've developed nanotheranostics (IN-DPPCO NPs) based on conjugated polymer IN-DPP and carbon monoxide (CO) carrier polymer mPEG(CO) for photothermal augmented gas therapy. The IN-DPPCO NPs can release CO with the hydrogen peroxide (H2O2) overexpressed in the tumor microenvironment. Meanwhile, IN-DPPCO NPs exhibit strong absorption in the near-infrared window, showing a high photothermal conversion efficiency of up to 41.5% under 808 nm laser irradiation. In vitro and in vivo experiments demonstrate that these nanotheranostics exhibit good biocompatibility. Furthermore, the synergistic CO/photothermal therapy shows enhanced therapeutic efficacy compared to gas therapy alone. This work highlights the great promise of conjugated polymer nanoparticles as versatile nanocarriers for spatiotemporally controlled and on-demand delivery of gaseous messengers to achieve precision cancer theranostics.

Metal carbonyl complexes possess among the most storied histories of any compound class in organometallic chemistry. Nonetheless, these old dogs continue to be taught new tricks. In this Feature, we review the historic discoveries and recent advances in cleaving robust bonds (e.g., C-H, C-O, C-F) using carbonyl complexes of three metals: Mn, Fe, and Co. The use of Mn, Fe, and Co carbonyl catalysts in controlling selectivity during hydrofunctionalization reactions is also discussed. The chemistry of these earth-abundant metals in the field of robust bond functionalization is particularly relevant in the context of sustainability. We expect that an up-to-date perspective on these seemingly simple organometallic species will emphasize the wellspring of reactivity that continues to be available for discovery.

The objective of this study is to design and synthesize substituted η⁶-chromium(0) tricarbonyl metal complexes carrying o-carborane units as potential boron neutron capture therapy (BNCT) agents. In this study, 1,2-diphenyl-o-carborane (1) units were used as starting materials to generate biologically active species. We investigated how the structural changes of 1 substituted with chromium(0) tricarbonyl affect the biological properties, and 1-(Phenyl-η⁶-chromium(0) tricarbonyl)-2-phenyl-o-carborane (2) and 1,2-bis(phenyl-η⁶-chromium(0) tricarbonyl)-o-carborane (3) species were produced in moderate yields. The molecular structures of compounds 1-3 were identified and established by infrared (IR); ¹H, ¹¹B, and ¹³C nuclear magnetic resonance (NMR) and X-ray crystallography analyses. Crystal structures of 1,2-diphenyl-o-carborane and the corresponding chromium complexes 1, 2, and 3 were obtained. In an in vitro study using B16 and CT26 cancer cells containing the triphenyl-o-carboranyl chromium(0) complexes Ph3C2BCr2 and Ph3C2BCr3, which we reported previously, compounds 2 and 3 accumulated at higher levels than compounds Ph3C2BCr2 and Ph3C2BCr3. However, the phenylated o-carboranyl chromium complexes have been found to be more cytotoxic than p-boronophenylalanine (BPA).

Aim: To test the antimicrobial effect of carbon monoxide-releasing molecules (CORMs) conjugated with azoles on different microorganisms. Methods & results: We used broth microdilution, checkerboard and cytotoxicity assays, as well as imaging, fluorescence and bioluminescence experiments to study [Re(CO)3(2,2'-bipyridyl)(Ctz)]+ (also known as ReBpyCtz). ReBpyCtz exhibits a low minimum inhibitory concentration value, increases the intracellular formation of reactive oxygen species and causes significant alterations on Staphylococcus aureus's membrane. ReBpyCtz is active against fungi, having a more prolonged fungicidal effect on Candida glabrata than clotrimazole and is selectively active on blood-stage malaria parasites, at a concentration that is not toxic to kidney epithelial cells. Conclusion: Conjugated CORMs have the potential to be active against different types of pathogens, thus constituting a promising class of broad-spectrum antimicrobials.

Three sawhorse-type ruthenium(I) complexes containing purine analogs such as triazolopyrimidines of the general formula [Ru₂(CO)₄(μ-OOCCH₃)₂(L)₂], where L is 1,2,4-triazolo[1,5-a]pyrimidine (tp for 1), 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine (dbtp for 2) and 5,7-diphenyl-1,2,4-triazolo[1,5-a]pyrimidine (dptp for 3), have been synthesized and characterized by elemental analysis, infrared analysis, multinuclear magnetic resonance spectroscopic techniques (¹H, ¹³C, ¹⁵N), and single-crystal X-ray diffraction (for 1 and 2). By assay with myoglobin, the photo-activated CO-releasing molecule (PhotoCORM) character of (1-3) has been confirmed, thus indicating the possibility of use in CO-based therapies. The importance of UV-induced modification has been investigated in the context of anticancer properties. Complexes (1) and (2) have been thoroughly screened for their in vitro cytotoxicity against various cancer cell lines: MCF-7 (breast cancer), HeLa (cervical cancer) and C32 (melanoma), as well as L929 normal fibroblasts in the dark and presence of UV-A light (365 nm). The results were compared with those for cisplatin and two reference ruthenium complexes, namely NAMI-A and KP1019. The most hydrophilic [Ru₂(CO)₄(μ-OOCCH₃)₂(tp)₂] (1) (log P = -1.12) was found to be more cytotoxic than (2), despite the lower cellular uptake measured by ICP-MS toward HeLa cells. Importantly, photo-induced stimulation of cells with (1) resulted in a lower decrease in the viability of L929 normal cells (IC₅₀ = 154.7 ± 6.5 μM) in comparison with HeLa cancer cells (IC₅₀ = 66.7 ± 3.4 μM). The photo-induced stimulation of (1) and (2) increases ROS generation, and their anticancer activity may be a partially ROS-dependent phenomenon.

Microglia, the 'resident immunocompetent cells' of the central nervous system (CNS), are key players in innate immunity, synaptic refinement and homeostasis. Dysfunctional microglia contribute heavily to creating a toxic inflammatory milieu, a driving factor in the pathophysiology of several CNS disorders. Therefore, strategies to modulate the microglial function are required to tackle exacerbated tissue inflammation. Carbon monoxide (CO), an endogenous gaseous molecule produced by the degradation of haem, has anti-inflammatory, anti-apoptotic, and pro-homeostatic and cytoprotective roles, among others. ALF-826A, a novel molybdenum-based CO-releasing molecule, was used for the assessment of neuron-microglia remote communication. Primary cultures of rat microglia and neurons, or the BV-2 microglial and CAD neuronal murine cell lines, were used to study the microglia-neuron interaction. An approach based on microglial-derived conditioned media in neuronal culture was applied. Medium derived from CO-treated microglia provided indirect neuroprotection against inflammation by limiting the lipopolysaccharide (LPS)-induced expression of reactivity markers (CD11b), the production of reactive oxygen species (ROS) and the secretion of inflammatory factors (TNF-α, nitrites). This consequently prevented neuronal cell death and maintained neuronal morphology. In contrast, in the absence of inflammatory stimulus, conditioned media from CO-treated microglia improved neuronal morphological complexity, which is an indirect manner of assessing neuronal function. Likewise, the microglial medium also prevented neuronal cell death induced by pro-oxidant tert-Butyl hydroperoxide (t-BHP). ALF-826 treatment reinforced microglia secretion of Interleukin-10 (IL-10) and adenosine, mediators that may protect against t-BHP stress in this remote communication model. Chemical inhibition of the adenosine receptors A_2A and A₁ reverted the CO-derived neuroprotective effect, further highlighting a role for CO in regulating neuron-microglia communication via purinergic signalling. Our findings indicate that CO has a modulatory role on microglia-to-neuron communication, promoting neuroprotection in a non-cell autonomous manner. CO enhances the microglial release of neurotrophic factors and blocks exacerbated microglial inflammation. CO improvement of microglial neurotrophism under non-inflammatory conditions is here described for the first time.

A one-pot synthetic route has been developed for the assembly of peptide Mn(i)-carbonyl bioconjugates. It allows the installation of a variety of chelating agents at the late stage, and after just one purification step the TAT-MnCO complexes can be obtained. The resulting bioconjugates showed different and tunable CO releasing kinetics upon visible light activation.

The homoleptic group 5 carbonylates [M(CO)6 ]- (M=Nb, Ta) serve as ligands in carbonyl-terminated heterobimetallic Agm Mn clusters containing 3 to 11 metal atoms. Based on our serendipitous [Ag6 {Nb(CO)6 }4 ]2+ (4 a2+ ) precedent, we established access to such Agm Mn clusters of the composition [Agm {M(CO)6 }n ]x (M=Nb, Ta; m=1, 2, 6; n=2, 3, 4, 5; x=1-, 1+, 2+). Salts of those molecular cluster ions were synthesized by the reaction of [NEt4 ][M(CO)6 ] and Ag[Al(ORF )4 ] (RF =C(CF3 )3 ) in the correct stoichiometry in 1,2,3,4-tetrafluorobenzene at -35 °C. The solid-state structures were determined by single-crystal X-ray diffraction methods and, owing to the thermal instability of the clusters, a limited scope of spectroscopic methods. In addition, DFT-based AIM calculations were performed to provide an understanding of the bonding within these clusters. Apparently, the clusters 3+ (m=6, n=5) and 42+ (m=6, n=4) are superatom complexes with trigonal-prismatic or octahedral Ag6 superatom cores. The [M(CO)6 ]- ions then bind through three CO units as tridentate chelate ligands to the superatom core, giving overall structures related to tetrahedral AX4 (42+ ) or trigonal bipyramidal AX5 molecules (3+ ).

Two photoactivatable dicarbonyl ruthenium(II) complexes based on an amide-functionalised bipyridine scaffold (4-position) equipped with an alkyne functionality or a green-fluorescent BODIPY (boron-dipyrromethene) dye have been prepared and used to investigate their light-induced decarbonylation. UV/Vis, FTIR and 13 C NMR spectroscopies as well as gas chromatography and multivariate curve resolution alternating least-squares analysis (MCR-ALS) were used to elucidate the mechanism of the decarbonylation process. Release of the first CO molecule occurs very quickly, while release of the second CO molecule proceeds more slowly. In vitro studies using two cell lines A431 (human squamous carcinoma) and HEK293 (human embryonic kidney cells) have been carried out in order to characterise the anti-proliferative and anti-apoptotic activities. The BODIPY-labelled compound allows for monitoring the cellular uptake, showing fast internalisation kinetics and accumulation at the endoplasmic reticulum and mitochondria.

As a continuation of our strategy for preparing new Ru(ii) precursors to be exploited as building blocks in the construction of metal-mediated supramolecular assemblies with improved solubility in water, here we describe the reactivity of selected neutral Ru(ii)-PTA carbonyls (PTA = 1,3,5-triaza-7-phosphaadamantane) towards the model imine ligands pyridine (py) and 2,2'-bipyridine (bpy) and the preparation and characterization of several neutral and cationic water-soluble derivatives: trans,trans,trans-[RuCl2(CO)(py)(PTA)2] (7), cis,cis,trans-[RuCl2(CO)2(py)(PTA)] (9), cis,trans-[Ru(bpy)Cl(CO)(PTA)2]Cl (10), mer-[Ru(bpy)(CO)(PTA)3](Cl)2 (12), cis,trans-[Ru(bpy)(CO)2Cl(PTA)]Cl (13), cis,trans-[Ru(bpy)(CO)2(PTA)2](NO3)2 (14NO3). In addition, we found that light-induced isomerization in some bpy compounds could be induced. The following species, either side-products isolated in low yield or compounds obtained exclusively in solution, were also unambiguously identified: cis,cis,trans-[RuCl2(CO)(py)(PTA)2] (8), trans-[RuCl2(bpy)(CO)(PTA)] (11), cis,cis-[Ru(bpy)Cl(CO)(PTA)2]Cl (15) and cis,cis-[Ru(bpy)(CO)2Cl(PTA)]Cl (16). The X-ray structures of 7, 11·H2O, and 12·7H2O are also reported. All compounds are new and - with few exceptions - show a good solubility in water.

Metal-organic frameworks (MOFs) comprising metal ions or clusters coordinated to organic ligands have become a class of emerging materials in the field of biomedical research due to their bespoke compositions, highly porous nanostructures, large surface areas, good biocompatibility, etc. So far, many MOFs have been developed for imaging and therapy purposes. The unique porous nanostructures render it possible to adsorb and store various substances, especially for gaseous molecules, which is rather challenging for other types of delivery vectors. In this review, we mainly focus on the recent development of MOFs for controlled release of three gaseous transmitters, namely, nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S). Although these gaseous molecules have been known as air pollutants for a long time, much evidence has been uncovered regarding their important physiological functions as signaling molecules. These signaling molecules could be either physically absorbed onto or covalently linked to MOFs, allowing for the release of loaded signaling molecules in a spontaneous or controlled manner. We highlight the designing concept by selective examples and display their potential applications in many fields such as cancer therapy, wound healing, and anti-inflammation. We hope more effort could be devoted to this emerging fields to develop signaling molecule-releasing MOFs with practical applications.

Nature provides a large number of functional proteins that evolved during billions of years of evolution. The diversity of natural proteins encompasses versatile functions and more than a thousand different folds, which, however, represents only a tiny fraction of all possible folds and polypeptide sequences. Recent advances in the rational design of proteins demonstrate that it is possible to design de novo protein folds unseen in nature. Novel protein topologies have been designed based on similar principles as natural proteins using advanced computational modelling or modular construction principles, such as oligomerization domains. Designed proteins exhibit several interesting features such as extreme stability, designability of 3D topologies and folding pathways. Moreover, designed protein assemblies can implement symmetry similar to the viral capsids, while, on the other hand, single-chain pseudosymmetric designs can address each position independently. Recently, the design is expanding towards the introduction of new functions into designed proteins, and we may soon be able to design molecular machines.

Carbon monoxide-releasing molecules (CORMs) are a special class of organometallic complexes that have been reported to offer beneficial effects against different conditions including several subtypes of cancer. Especially for the aggressive and poorly treated triplenegative breast cancer (TNBC), early CORMs have been shown to diminish malignant angiogenesis and may be considered as an alternative approach. So, this study aimed at testing novel CORM molecules against angiogenesis in TNBC seeking potent drug candidates for new therapies.

Based on previous studies, CORM-3 was chosen as the lead compound and a group of 15 new ruthenium-based CORMs was synthesized and subsequently evaluated in vitro for potential anti-angiogenic properties.

A similar anti-angiogenic behaviour to the lead complex was observed and a new CORM, complex 4, emerged as a promising agent from this study. Specifically, this complex offered better inhibition of the activation of VEGFR2 and other downstream proteins of vascular endothelial cells. Complex 4 also retained the ability of the parent molecule to reduce the upregulated VEGF expression from TNBC cells and inhibit endothelial cell migration and new vessel formation. The lack of significant cytotoxicity and the downregulating activity over the cytoprotective enzyme haem oxygenase-1 (HO-1) in cancer cells may also favour CORMs against this poorly treated subtype of breast cancer.

Since the anti-angiogenic approach is one of the few available targeted strategies against TNBC, both CORM-3 and the new complex 4 should be considered for further research as combination agents with existing anti-angiogenic drugs for more effective treatment of malignant angiogenesis in TNBC.

Interest in the therapeutic effects of carbon monoxide (CO), a product of heme degradation catalyzed by the enzyme heme oxygenase-1 (HO-1), has led to the development of CO-releasing molecules (CO-RMs) for the controlled delivery of this gas in vivo. We recently proposed conjugating a cobalt-based CO-RM with various activators of nuclear factor erythroid 2-related factor 2 (Nrf2), the transcription factor that regulates HO-1 expression, in order to exploit the beneficial effects of exogenous and endogenous CO. In this study, we describe the preparation of hybrid molecules (termed HYCOs) conjugating a fumaric acid derivative as an Nrf2 activator to a Mn- or a Ru-based CO-RM known to be pharmacologically active. With the exception of an acyl-manganese complex, these hybrids were obtained by associating the two bioactive entities by means of a linker of variable structure. X-ray diffraction analyses and preliminary biological investigations are also presented.

Carbon monoxide (CO) is regarded as a potential therapeutic agent with multiple beneficial functions for biomedical applications. In this study, a versatile CO nanogenerator (designated as PPOSD) was fabricated and developed for tumor therapy and anti-inflammation. Partially oxidized tin disulfide (SnS₂) nanosheets (POS NSs) were decorated with a tumor-targeting polymer (polyethylene glycol-cyclo(Asp-d-Phe-Lys-Arg-Gly), PEG-cRGD), followed by the loading of chemotherapeutic drug doxorubicin (DOX) to prepare polymer@POS@DOX, or PPOSD. After injected intravenously, PPOSD could selectively accumulate in tumor tissue via the cRGD-mediated tumor recognition. Upon 561 nm laser irradiation, the POS moiety in PPOSD can photoreduce CO₂ to CO, which significantly sensitized the chemotherapeutic effect of DOX. The POS in PPOSD can also act as a photothermal agent for effective photothermal therapy (PTT) of the tumor upon 808 nm laser irradiation. Furthermore, the generated CO can simultaneously decrease the inflammatory reaction caused by PTT. Blood analysis and hematoxylin-eosin staining of major organs showed that no obvious systemic toxicity was induced after the treatment, suggesting good biosafety of PPOSD. This versatile CO nanogenerator will find great potential for both enhanced tumor inhibition and anti-inflammation.

The present study aimed to investigate the effect of carbon monoxide (CO)‑releasing molecule‑2 (CORM‑2) on pancreatic function in sepsis‑model mice. To perform the present investigation, mice were rendered septic by cecal ligation and puncture (CLP). Then, mice were either treated with or without CORM‑2 (8 mg/kg, intravenous) for different durations (6, 12 and 24 h) immediately following CLP. The levels of serum amylase and lipase, tumor necrosis factor α, interleukin‑1β and interleukin‑6 in addition to myeloperoxidase (MPO) activity in pancreatic tissues were determined at 6, 12 and 24 h post‑CLP. Histological scores and the expression of intercellular adhesion molecule 1 (ICAM‑1), vascular cell adhesion molecule 1 (VCAM‑1), nuclear factor‑κB (NF‑κB) and phosphorylated inhibitor of κB (p‑IκB‑α) in the pancreas were also evaluated at 24 h post‑CLP. The results of the present study revealed that compared with CLP‑alone group, CORM‑2 treatment significantly (P<0.05) reduced the levels of serum amylase, lipase and pro‑inflammatory cytokines. In parallel, the severity of pancreatic histology, MPO activity and the expression levels of ICAM‑1 and VCAM‑1 in the pancreas of CORM‑2 treated CLP mice were substantially decreased compared with the untreated group. Furthermore, CORM‑2 treatment inhibited the expression levels of NF‑κB and P‑IκB‑α in the pancreas of mice following CLP compared with the untreated group. CORM‑2‑liberated CO exerted protective effects on the pancreatic function of septic mice, and the beneficial effects may be due to the suppression of NF‑κB activation and subsequent regulation of NF‑κB‑dependent expression of cytokines.

Four diiron(ii) carbonyl complexes, [Fe2(μ-SR)3(CO)5X] (X- = Br-, I-; R = CH2CH3, CH2CH2CH3) were facilely synthesized by reacting [Fe(CO)4X2] with monothiolates. Their potential as carbon monoxide-releasing molecules (CORMs) was systematically investigated, revealing that their CO-releasing behaviour is highly solvent-dependent. Specifically, in dimethyl sulfoxide (DMSO), the CO-releasing kinetics were fast. Intermediates with a lower oxidation state might be involved in the reaction. By contrast, in less polar solvents such as methanol, acetonitrile and dichloromethane, intermediates featuring the triiron carbonyl cation, [Fe3(μ-SCH2CH3)6(CO)6]+, were isolated. The triiron intermediate underwent further decomposition to liberate CO. One of the iodo complexes was also examined for its CO-release in PBS solution when solubilised with DMSO in the presence of deoxy-Mb and the CO-release was found to be quantitative. Furthermore, kinetic analyses were performed and the CO-release in general obeyed a first-order kinetic model. Plausible CO-releasing pathways are proposed for the parent complexes and the triiron intermediate. Assessments in cytotoxicity indicated that the cytoxicity of the diiron(ii) complexes varied with both the halide and thiolate and those bearing bromide and the thiolate with longer chains were more biocompatible.

Tip-enhanced Raman spectroscopy (TERS) is capable of probing specific molecular information with high sensitivity, but dual chemical sensing remains a challenge. Another major hindrance to TERS chemical detection in biosamples such as blood is the interference from the strong absorptions of biomolecules. Herein, we report the preparation of an organometallic-conjugated TERS tip. We demonstrate that organometallic chemistry can be perfectly coupled with TERS for dual-molecule sensing. The unique Raman signals generated by the organometallic compound circumvent signal interference from the biomolecules in blood, allowing the rapid analysis of two important molecules (glucose and thiol) in ultralow volume (50 nL) samples. This enabled a correlation between the thiol and glucose levels in the blood of nondiabetic and diabetic patients to be drawn.

CO-releasing molecules (CORMs) containing cobalt have many bioactivities, but most of them do not dissolve in water and have no selectivity to tissue and organs. On the basis of the specific recognition of galactose or sialic acid by a receptor, a series of CORMs based on carbohydrates were synthesized and evaluated. The test results show that all the complexes displayed anticancer activity. Among them, the effects of the complexes of galactose (1), GalNAc (8) and sialic acid (10) were very distinct. Complex 1 displayed higher activity against HeLa, HePG2, MCF-7 and HT-29 cell proliferation than cis-platin (DDP), and its selectivity was far much better than DDP compared with normal cell W138. Furthermore, the uptakes of complexes 1, 8 and 10 by HePG2, HT-29, A549 and RAW264.7 cell lines were studied. The uptake ratio of each cell line for complex 1 was different, and the order of uptake ratio in the four cell lines was HePG2 > HT-29 > RAW264.7 > A549. The HePG2 cells absorbed complex 1 beyond 60% after incubation for 8 h, while A549 absorbed only 27.8%. For complex 8, the uptake trend was similar to that of complex 1 with it being absorbed by all the four cancer cells, but the uptake rate was lower. However, differently, complex 10 was absorbed heavily by macrophage RAW264.7, followed by HePG2; after 8 h incubation, the uptake ratio of RAW264.7 was over 50%. In addition, the mechanism of action was explored, and the results showed that the complexes inhibited cell cycle arrest at the G2/M phase; complex 1 up-regulated the expression levels of caspase-3 and Bax, and down-regulated the Bcl-2 expression, giving rise to HePG2 cell apoptosis.

The recognized therapeutic benefits from carbon monoxide (CO) have caused booming attention to develop a CO therapy for various major diseases, such as cancer. However, the controlled release of CO gas and the monitoring of the CO release are vitally important to the on-demand CO administration for a safe and efficient therapy, but greatly challenging. In this work, a new CO-releasing nanocomplex was constructed by the adsorption and coordination of manganese carbonyl ([MnBr(CO)₅ ], abbreviated as MnCO) with a Ti-based metal-organic framework (Ti-MOF) to realize an intratumoral H₂ O₂ -triggered CO release and real-time CO release monitoring by fluorescence imaging. A high CO prodrug loading capacity (0.532 g MnCO per gram Ti-MOF) is achieved due to the high surface area of Ti-MOF, and the intracellular H₂ O₂ -triggered CO release from the MnCO@Ti-MOF is realized to enable the nanocomplex selectively release CO in tumor cells and kill tumor cells rather than normal cells. Particularly significant is that the real-time fluorescence imaging monitoring of the CO release is realized based on an annihilation effect of the fluorescence after MnCO loading into Ti-MOF and an activation effect of the fluorescence after CO release from Ti-MOF. The quantitative relationship between the fluorescence intensity and the released CO amount is established in great favor of guiding on-demand CO administration. The results demonstrate the advantage of versatile MOFs for high efficient CO delivery and monitoring, which is critical for the improvement of the effectiveness of future therapeutic application.

By taking advantage of the spectral properties of metal carbonyls, we have designed a surface-enhanced Raman spectroscopy (SERS) ratiometric assay for measuring cell-free circulating DNA (cfDNA) from Epstein-Barr virus in blood for nasopharyngeal carcinoma (NPC). This assay consists of a rhenium carbonyl (Re-CO) to serve as a DNA probe, an osmium carbonyl (Os-CO) embedded within the SERS-active substrate as an internal reference, and a streptavidin layer on the surface of the substrate. Hybridization of cfDNA with biotinylated-capture sequence leads to immobilization of cfDNA on the substrate. The binding of Re-CO via daunorubicin (DNR) to cfDNA is accompanied by an appearance of a strong symmetry stretching vibrations peak at 2113 cm^-1, which has spectral overlap with Os-CO (2025 cm^-1). This results in an increase in the I₂₁₁₃/ I₂₀₂₅ ratio and quantitatively correlates with cfDNA. This SERS assay can be readily used to detect cfDNA in blood samples from patients due to the intensity ratio of I₂₁₁₃/ I₂₀₂₅ lying in a silent region (1780-2200 cm^-1) in the SERS spectrum of the biomolecules.

Reactions of dicobalt octacarbonyl [Co2(CO)8] with 2'-deoxy-5-oxopropynyluridines and related compounds gave dicobalt hexacarbonyl nucleoside complexes (83-31 %). The synthetic outcomes were confirmed by X-ray structure determination of dicobalt hexacarbonyl 2'-deoxy-5-(4-hydroxybut-1-yn-1-yl)uridine, which exhibits intermolecular hydrogen bonding between a modified base and ribose. The electronic structure of this compound was characterized by the DFT calculations. The growth inhibition of HeLa and K562 cancer cell lines by organometallic nucleosides was examined and compared to that by alkynyl nucleoside precursors. Coordination of the dicobalt carbonyl moiety to the 2'-deoxy-5-alkynyluridines led to a significant increase in the cytotoxic potency. The cobalt compounds displayed antiproliferative activities with median inhibitory values (IC50) in the range of 20 to 80 μm for the HeLa cell line and 18 to 30 μm for the K562 cell line. Coordination of an acetyl-substituted cobalt nucleoside was expanded by using the 1,1-bis(diphenylphosphino)methane (dppm) ligand, which exhibited cytotoxicity at comparable levels. The formation of reactive oxygen species in the presence of cobalt compounds was determined in K562 cells. The results indicate that the mechanism of action for most antiproliferative cobalt compounds may be related to the induction of oxidative stress.