Corm Research Articles

Development of carbon monoxide-releasing molecules conjugated to polysaccharides (glyco-CORMs) for delivering CO during obesity

Metal carbonyls have been developed as carbon monoxide-releasing molecules (CO-RMs) to deliver CO for therapeutic purposes. The manganese-based CORM-401 has been recently reported to exert beneficial effects in obese animals by reducing body weight gain, improving glucose metabolism and reprogramming adipose tissue towards a healthy phenotype. Here, we report on the synthesis and characterization of glyco-CORMs, obtained by grafting manganese carbonyls on dextrans (70 and 40 kDa), based on the fact that polysaccharides facilitate the targeting of drugs to adipose tissue. We found that glyco-CORMs efficiently deliver CO to cells in vitro with higher CO accumulation in adipocytes compared to other cell types. Oral administration of two selected glyco-CORMs (5b and 6b) resulted in CO accumulation in various organs, including adipose tissue. In addition, glyco-CORM 6b administered for eight weeks elicited anti-obesity and positive metabolic effects in mice fed a high fat diet. Our study highlights the feasibility of creating carriers with multiple functionalized CO-RMs.

Spectroscopical and Molecular Studies of Four Manganese(I) PhotoCORMs with Bioinspired Ligands Containing Non-Coordinated Phenol Groups.

Carbonyl compounds are widely explored in medicinal inorganic chemistry and have drawn attention due to their signaling functions in homeostasis. Carbon-monoxide-releasing molecules (CORMs) were developed with the purpose of keeping the CO inactive until its release in the intracellular environment, considering its biological relevance. However, for therapeutic applications, the mechanisms of photorelease and which electronic and structural variations influence its rates must be fully understood. In this work, four ligands containing a pyridine, a secondary amine, and a phenolic group with different substituents were used to prepare new Mn(I) carbonyl compounds. Structural and physicochemical characterization of these complexes was carried out and confirmed the proposed structures. X-ray diffractometry structures obtained for the four organometallic compounds revealed that the substituents in the phenolic ring promote only negligible distortions in their geometry. Furthermore, UV-Vis and IR kinetics showed the direct dependence of the electron-withdrawing or donating ability of the substituent group, indicating an influence of the phenol ring on the CO release mechanism. These differences in properties were also supported by theoretical studies at the DFT, TD-DFT, and bonding situation analyses (EDA-NOCV). Two methods were used to determine the CO release constants (kCO,old and kCO,new), where Mn-HbpaBr (1) had the greatest kCO by both methods (Kco,old = 2.36 × 10-3 s-1 and kCO,new = 2.37 × 10-3 s-1). Carbon monoxide release was also evaluated using the myoglobin assay, indicating the release of 1.248 to 1.827 carbon monoxides upon light irradiation.

MP60-07 BRAIN CARBON MONOXIDE SUPPRESSES THE RAT MICTURITION VIA BRAIN GABA RECEPTORS

You have accessJournal of UrologyCME1 Apr 2023MP60-07 BRAIN CARBON MONOXIDE SUPPRESSES THE RAT MICTURITION VIA BRAIN GABA RECEPTORS Masaki Yamamoto, Takahiro Shimizu, Suo Zou, Shogo Shimizu, Youichirou Higashi, Mikiya Fujieda, and Motoaki Saito Masaki YamamotoMasaki Yamamoto More articles by this author , Takahiro ShimizuTakahiro Shimizu More articles by this author , Suo ZouSuo Zou More articles by this author , Shogo ShimizuShogo Shimizu More articles by this author , Youichirou HigashiYouichirou Higashi More articles by this author , Mikiya FujiedaMikiya Fujieda More articles by this author , and Motoaki SaitoMotoaki Saito More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003318.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Carbon monoxide (CO) is a well-known toxic gas but is also reported as a gasotransmitter besides nitric oxide and hydrogen sulfide. Endogenous CO is produced by heme oxygenase (HO)-induced heme catabolism and shows physiological functions such as anti-inflammation and neuromodulation. In this study, we examined effects of centrally administered CORM3 (CO donor) and ZnPP (HO inhibitor) on the rat micturition. METHODS: Urethane anesthetized (0.8 g/kg, ip) male Wistar rats (350-450 g) were used. A catheter was inserted into the bladder to perform continuous cystometry (12 ml/h saline infusion). Three hours after the surgery, CORM3 (1 or 10 nmol/rat), ZnPP (10 or 30 nmol/rat) or vehicle was intracerebroventricularly (ICV) administered. In some rats, effects of ICV pretreated SR95531 (SR, GABAA antagonist, 0.1 nmol/rat) on the CORM3 (10 nmol/rat, ICV)-induced responses were examined. Continuous cystometry and evaluation of intercontraction intervals (ICI) and maximal voiding pressure (MVP) were started 30 min before the first ICV administration. In some rats, before and after ZnPP administration (30 nmol/rat, ICV), single cystometry (12 ml/h saline infusion) was performed. RESULTS: CORM3 dose-dependently prolonged ICI without changing MVP (Figure 1A-B). On the other hand, ZnPP dose-dependently shortened ICI without changing MVP (Figure 1C-D). In single cystometry, ZnPP significantly reduced single-voided volume and bladder capacity without changing post-voiding residual volume (Table 1). The ZnPP (30 nmol/rat, ICV)-induced ICI shortening was reversed in the central presence of CORM3 (10 nmol/rat, ICV) (Figure 2). The CORM-3-induced ICI prolongation was suppressed by SR (Figure 3). CONCLUSIONS: Brain CO endogenously suppresses the rat micturition via brain GABAA receptors. Thus, the brain CO might be a new therapeutic target for neurogenic bladder overactivity. Source of Funding: JSPS KAKENHI (#21K09428, #20K07827) © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e845 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Masaki Yamamoto More articles by this author Takahiro Shimizu More articles by this author Suo Zou More articles by this author Shogo Shimizu More articles by this author Youichirou Higashi More articles by this author Mikiya Fujieda More articles by this author Motoaki Saito More articles by this author Expand All Advertisement PDF downloadLoading ...

5-Aminolevrinic Acid Exhibits Dual Effects on Stemness in Human Sarcoma Cell Lines under Dark Conditions.

5-aminolevulinic acid (ALA) is used for tumor-targeting phototherapy because it is converted to protoporphyrin IX (PPIX) upon excitation and induces phototoxicity. However, the effect of ALA on malignant cells under unexcited conditions is unclear. This information is essential when administering ALA systemically. We used sarcoma cell lines that usually arise deep in the body and are rarely exposed to light to examine the effects of ALA treatment under light (daylight lamp irradiation) and dark (dark room) conditions. ALA-treated human SW872 liposarcoma cells and human MG63 osteosarcoma cells cultured under light exhibited growth suppression and increased oxidative stress, while cells cultured in the dark showed no change. However, sphere-forming ability increased in the dark, and the expression of stem-cell-related genes was induced in dark, but not light, conditions. ALA administration increased heme oxygenase 1 (HO-1) expression in both cell types; when carbon monoxide (CO), a metabolite of HO-1, was administered to sarcoma cells via carbon-monoxide-releasing molecule 2 (CORM2), it enhanced sphere-forming ability. We also compared the concentration of biliverdin (BVD) (a co-product of HO-1 activity alongside CO) with sphere-forming ability when HO-1 activity was inhibited using ZnPPIX in the dark. Both cell types showed a peak in sphere-forming ability at 60-80 μM BVD. Furthermore, a cell death inhibitor assay revealed that the HO-1-induced suppression of sphere formation was rescued by apoptosis or ferroptosis inhibitors. These findings suggest that in the absence of excitation, ALA promotes HO-1 expression and enhances the stemness of sarcoma cells, although excessive HO-1 upregulation induces apoptosis and ferroptosis. Our data indicate that systemic ALA administration induces both enhanced stemness and cell death in malignant cells located in dark environments deep in the body and highlight the need to pay attention to drug delivery and ALA concentrations during phototherapy.

A simple ratiometric fluorescent probe for two-photon imaging of carbon monoxide in living cells and zebrafish

Carbon monoxide (CO) is an important gas signaling molecule and has been widely involved in regulating important life processes. Effective monitoring of CO in living systems is critical. Combined with the accuracy of ratio detection and the advantages of two-photon imaging, a simple ratiometric two-photon fluorescent probe RTFP was rationally designed and synthesized using 7-(diethylamino)-4-hydroxycoumarin as a two-photon fluorophore and allyl carbonate as the reactive unit. Probe RTFP exhibited excellent selectivity and sensitivity towards CO, and was successfully applied to image endogenous CO in living cells and zebrafish.

Fabrication of CO-releasing surface to enhance the blood compatibility and endothelialization of TiO2 nanotubes on titanium surface

Although the construction of nanotube arrays with the micro-nano structures on the titanium surfaces has demonstrated a great promise in the field of blood-contacting materials and devices, the limited surface hemocompatibility and delayed endothelial healing should be further improved. Carbon monoxide (CO) gas signaling molecule within the physiological concentrations has excellent anticoagulation and the ability to promote endothelial growth, exhibiting the great potential for the blood-contact biomaterials, especially the cardiovascular devices. In this study, the regular titanium dioxide nanotube arrays were firstly prepared in situ on the titanium surface by anodic oxidation, followed by the immobilization of the complex of sodium alginate/carboxymethyl chitosan (SA/CS) on the self-assembled modified nanotube surface, the CO-releasing molecule (CORM-401) was finally grafted onto the surface to create a CO-releasing bioactive surface to enhance the biocompatibility. The results of scanning electron microscopy (SEM), X-ray energy dispersion spectroscopy (EDS), and X-ray photoelectron spectroscopy (XPS) revealed that the CO-releasing molecules were successfully immobilized on the surface. The modified nanotube arrays not only exhibited excellent hydrophilicity but also could slowly release CO gas molecules, and the amount of CO release increased when cysteine was added. Furthermore, the nanotube array can promote albumin adsorption while inhibit fibrinogen adsorption to some extent, demonstrating its selective albumin adsorption; although this effect was somewhat reduced by the introduction of CORM-401, it can be significantly enhanced by the catalytic release of CO. The results of hemocompatibility and endothelial cell growth behaviors showed that, as compared with the CORM-401 modified sample, although the SA/CS-modified sample had better biocompatibility, in the case of cysteine-catalyzed CO release, the released CO could not only reduce the platelet adhesion and activation as well as hemolysis rate, but also promote endothelial cell adhesion and proliferation as well as vascular endothelial growth factor (VEGF) and nitric oxide (NO) expression. As a result, the research of the present study demonstrated that the releasing CO from TiO2 nanotubes can simultaneously enhance the surface hemocompatibility and endothelialization, which could open a new route to enhance the biocompatibility of the blood-contacting materials and devices, such as the artificial heart valve and cardiovascular stents.

Pre-conditioning of gingival epithelial cells with sub-apoptotic concentrations of curcumin prevents pro-inflammatory cytokine release.

Plaque-induced gingival inflammation (gingivitis) is ubiquitous in humans. The epithelial barrier reacts to the presence of oral bacteria and induces inflammatory cascades. The objective of this study was to investigate the mechanism by which the small molecule micronutrient curcumin could decrease inflammatory response in vitro to oral bacterium heat-killed Fusobacterium nucleatum as curcumin could be a useful compound for combatting gingivitis already consumed by humans. H400 oral epithelial cell line was pre-conditioned with curcumin and the production of cytokines was measured by enzyme-linked immunosorbent assay (ELISA) and translocation of transcription factors was used to monitor inflammatory responses. Haem oxygenase (HO-1) expression and molecules that HO-1 releases were evaluated for their potential to reduce the quantity of cytokine production. Immunofluorescence microscopy and Western blotting were used to evaluate changes in transcription factor and enzyme location. Pre-conditioning of H400 cells with a sub-apoptotic concentration of curcumin (20 μM) attenuated secretion of Granulocyte-Macrophage - Colony-Stimulating Factor (GM-CSF) and reduced NFkB nuclear translocation. This pre-conditioning caused an increase in nuclear Nrf2; an initial drop (at 8h) followed by an adaptive increase (at 24 h) in glutathione; and an increase in haem oxygenase (HO-1) expression. Inhibition of HO-1 by SnPPIX prevented the curcumin-induced attenuation of GM-CSF production. HO-1 catalyses the breakdown of haem to carbon monoxide, free iron and biliverdin: the HO-1/CO anti-inflammatory pathway. Elevations in carbon monoxide, achieved using carbon monoxide releasing molecule-2 (CORM2) treatment alone abrogated F. nucleatum-induced cytokine production. Biliverdin is converted to bilirubin by biliverdin reductase (BVR). This pleiotropic protein was found to increase in cell membrane expression upon curcumin treatment. Curcumin decreased inflammatory cytokine production induced by Fusobacterium nucleatum in H400 oral epithelial cells. The mechanism of action appears to be driven by the increase of haem oxygenase and the production of carbon monoxide.

H2O2 responsive CO gas release platform with CA IX-Targeting for inhibiting tumor growth and metastasis

Carbon monoxide (CO) gas therapy has emerged as a highly promising anti-tumor strategy. However, targeting delivery and controlled intratumoral release of CO still have unsatisfactory outcomes. Herein, we constructed a novel CO therapeutic platform consisting of a carbonic anhydrase IX (CA IX) inhibitor (CAI) and intelligent responsive CO-releasing molecules (CORMs). The formed platform coupled with CAI can actively target CA IX overexpressed tumor cells to achieve targeted delivery of CORMs. After reaching the tumor site and being internalized by tumor cells, CORMs can be activated by the endogenous H2O2, realizing the light induced excited-state intramolecular proton transfer (ESIPT) effect and spatiotemporal controllable release of CO. Next, CAI can prevent tumor metastasis by inhibiting CA IX to alleviate the acidic tumor extracellular environment, while the generated CO can also achieve tumor metastasis inhibition by inhibiting vascular endothelial growth factor (VEGF). In vitro and in vivo experiments indicate that the constructed CO gas therapeutic platform can significantly inhibit tumor growth and metastasis, which provides a new direction for tumor gas therapy.

Endogenous carbon monoxide (CO) as a modulating factor of molecular biological clock in the hypothalamic structures involved in light transmission in pig and wild boar hybrid during long and short day season.

Mature males of a wild boar-pig crossbreed, during the long and short day season, were used for the study which demonstrates that the chemical light carrier CO regulates the expression of biological clock genes in the hypothalamus via humoral pathways. Autologous blood with experimentally elevated concentrations of endogenous CO (using lamps with white light-emitting diodes) was infused into the ophthalmic venous sinus via the right dorsal nasal vein. Molecular biology methods: qPCR and Western Blot were used to determine the expression of genes and biological clock proteins. The results showed that elevated endogenous CO levels, through blood irradiation, induces changes in genes expression involved in the functioning of the main biological clock located in suprachiasmatic nuclei. Changes in the expression of the transcription factors Bmal1, Clock and Npas2 have a similar pattern in both structures, where a very large decrease in gene expression was shown after exposure to elevated endogenous CO levels. The changes in the gene expression of PER 1-2, CRY 1-2, and REV-ERB α-β and ROR β are not the same for both POA and DH hypothalamic structures, indicating that both structures respond differently to the humoral signal received. The results indicate that CO is a chemical light molecule whose production in an organism depends on the amount of light. An adequate amount of light is an essential factor for the proper functioning of the main biological clock.

Carbon monoxide preconditioning is mediated via activation of mitochondrial-derived vesicles

Preconditioning with inhalative carbon monoxide (CO) at low concentrations provides protection against hypoxic and ischemic insults in the brain and heart. The present study aims to test a hypothesis that activation of mitochondrial-derived vesicles (MDVs) is a mechanism underlying the protective effect of CO preconditioning. Here we show that CO preconditioning induced mild oxidative stress and activated massive production of MDVs. Short exposure to a low concentration of carbon monoxide-releasing molecule 2 (CORM-2), a donor of carbon monoxide, prevented oligodendrocyte precursor cells (OPCs) from subsequent death induced by high doses of CO, and protected Chinese hamster ovary (CHO) cells against oxygen-glucose deprivation (OGD)-induced cell death. Furthermore, inhibition of lysosomal activity prevented degradation of MDVs, abolished MDV-mediated mitochondrial quality control, and diminished the protective effect of CO preconditioning. Altogether, our data provide direct evidence suggesting that MDV-mediated mitochondrial quality control may have a novel role in CO preconditioning.

A near-infrared HBT-based fluorescent probe for tracking carbon monoxide-releasing CORM-3

Tricarbonylchloro(glycinato)ruthenium (CORM-3) has important application in the treatment of clinical diseases because of anti-inflammatory and heart-protecting properties, and is also used to study the metabolic mechanism of endogenous carbon monoxide as a safe and convenient carbon monoxide-releasing agent in vivo due to good water solubility and releasing controlled amounts of CO. Thus the development of effective detection methods to achieve the analysis of CORM-3 is of great significance in monitoring CORM-3 and studying the specific mechanism of endogenous CO in biological samples. Herein a small molecule fluorescent probe was developed by selecting 2-(2-hydroxyphenyl)benzothiazole (HBT) derivative as the optical signal unit and 4-nitrobenzyl moiety as the reactive unit. It could quickly detect CORM-3 within 15 min by the enhanced near-infrared fluorescence at 720 nm without the participation of heavy metal ions, accompanied by the large Stokes movement of 195 nm. The detection limit and linear range of the probe toward CORM-3 were achieved 0.11 µM and 0 – 175 µM, respectively. Besides, this probe displayed a red-edge effect, and the excitation wavelength and emission wavelength may be adjusted reasonably according to the test requirement to avoid interference signal. More importantly, it has been successfully used for the detection of CORM-3 with high resolution of fluorescence imaging in living cells and Zebrafish.

Light activated simultaneous release and recognition of biological signaling molecule carbon monoxide (CO).

The therapeutic action of carbon monoxide (CO) is very well known and has been studied on various types of tissues and animals. However, real-time spatial and temporal tracking and release of CO is still a challenging task. This paper reported an amphiphilic CO sensing probe NP and phospholipid 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) based nanoscale vesicular sensing system Ves-NP consisting of NP. The liposomal sensing system (Ves-NP) showed good selectivity and sensitivity for CO without any interference from other relevant biological analytes. Detection of CO is monitored by fluorescence OFF-ON signal. Ves-NP displayed LOD of 5.94µM for CO detection with a response time of 5min. Further, in a novel attempt, Ves-NP is co-embedded with the amphiphilic CO-releasing molecule 1-Mn(CO)3 to make an analyte replacement probe Ves-NP-CO. Having a both CO releasing and sensing moiety at the surface of the same liposomal system Ves-NP-CO play a dual role. Ves-NP-CO is used for the simultaneous release and recognition of CO that can be controlled by light. Thus, in this novel approach, for the first time we have attached both the release and recognition units of CO in the vesicular surface, both release and recognition simultaneously monitored by the change in fluorescent OFF-ON signal.

Novel Insights on CAI-CORM Hybrids: Evaluation of the CO Releasing Properties and Pain-Relieving Activity of Differently Substituted Coumarins for the Treatment of Rheumatoid Arthritis.

Pain control is among the most important healthcare services in patients affected by rheumatoid arthritis (RA), but the current therapeutic options (i.e., disease-modifying anti-rheumatic drugs) are limited by the risk of the side effects. In this context, we proposed an innovative approach based on the hybridization between carbonic anhydrase inhibitors (CAIs) and CO releasing molecules (CORMs). The resulting CAI-CORM hybrids were revealed to possess strong anti-inflammatory effects in in vitro models of diseases and to relieve ache symptoms in an in vivo RA rat model. In this work, we have deepened the study of these promising hybrids, designing a library of coumarin-based compounds, also including internal dicobalt hexacarbonyl systems. The results obtained from the CO releasing study, the CA inhibitory activity, and the in vivo pain-relief efficacy evaluation in the RA rat model confirmed the success of this strategy, allowing us to consider CAI-CORM hybrids promising anti-nociceptive agents against arthritis.

A mitochondria-targeted fluorescent probe for imaging of endogenous carbon monoxide in living cells

Carbon monoxide (CO), a vital gasotransmitter, plays critical functions in many physiological processes. Mitochondrial CO is closely related to mitochondrial respiration, thus the detection and imaging of mitochondrial CO in living cells is very important and has attracted much attention recently. In this paper, we developed a hemicyanine-based off–on fluorescent probe, CO-H1, which was used for monitoring endogenous mitochondrial CO levels in living cells. After reacted with CO in the presence of PdCl2, the fluorescence of CO-H1 was enhanced notably, accompanied by a significant red shift of absorption. CO-H1 exhibits low cytotoxicity, high sensitivity (detection limit of 0.048 μM), and good selectivity for CO. When incubated with living cells, probe CO-H1 mainly entered the mitochondria. CO-H1 was successfully applied to imaging the exogenous/endogenous mitochondrial CO in living cells, suggesting its potential application for further studying the biological functions of mitochondrial CO in living cells.

Renal Clearable Catalytic 2D Au-Porphyrin Coordination Polymer Augmented Photothermal-Gas Synergistic Cancer Therapy.

As a gasotransmitter, carbon monoxide (CO) possesses antitumor activity by reversing the Warburg effect at higher concentrations. The targeted delivery of carbon monoxide-releasing molecules (CORMs) using nanomaterials is an appealing option for CO administration, but how to maintain CO above the threshold concentration in tumor tissue remains a challenge. Herein, a nanozyme-catalyzed cascade reaction is proposed to promote CO release for high-efficacy photothermal therapy (PTT)-combined CO therapy of cancer. A gold-based porphyrinic coordination polymer nanosheet (Au0 -Por) is synthesized to serve as a carrier for CORM. It also possesses excellent glucose oxygenase-like activity owing to ultrasmall zero-valent gold atoms on the nanosheet. The catalytically generated H2 O2 can efficiently catalyze CORM decomposition, which enables in situ generation of sufficient CO for gas therapy. In vivo, the Au0 -Por nanosheets-enhanced photoacoustic imaging (PAI) and fluorescence imaging collectively demonstrate high tumor-targeting efficiency and nanomaterial retention. Proven to have augmented therapeutic efficacy, the nanoplatform can also be easily degraded and excreted through the kidney, indicating good biocompatibility. Thus, the application of rational designed Au0 -Por nanosheet with facile approach and biodegradable property to PAI-guided synergistic gas therapy can provide a strategy for the development of biocompatible and highly effective gaseous nanomedicine.

Synthesis, structure, CO releasing, and biological activities of new 1-D chain Mn(I)/Mn(II) visible light activated CO-releasing molecules (CORMs)

The manganese tricarbonyl complex {[Mn2(CO)6Mn(H2O)4(BPDC)2]·2H2O}n (1) (BPDC = 2,2′-bipyridyl-4,4′-dicarboxylic acid) was synthesized from the reaction of MnBr(CO)5 with 2,2′-bipyridyl-4,4′-dicarboxylic acid. Various fac-Mn(CO)3 cores based on mononuclear complexes were achieved and only a handful of the Mn(I)-based dinuclear metallastirrups or supramolecular rectangles were reported. Interestingly, our compound is the first example of a CORM with 1-D ladder-like chain and Mn(I)/Mn(II) mixed valence state. Studies show that 1 can release CO under three different wavelengths of light (Green: λ = 520–530 nm; Blue: λ = 465–470 nm; UV: λ = 365–370 nm) and CO releasing rate can be adjusted by changing the wavelength of the irradiation light. Density functional theory (DFT) calculations were conducted to analyze the effect of metal-to-ligand charge transfer (MLCT) on CO releasing behaviors. Furthermore, cellular viability assay and anti-inflammatory activities showed that 1 possessed biological compatibility but no systemic cytotoxicity, and could prevent LPS-induced secretion of TNF-α and NO in RAW264.7 cells. The results suggest that 1 may provide a therapeutic approach for inflammation.

A novel red AIE fluorescent probe for ratiometric detection of carbon monoxide in vitro and in vivo.

As a significant signaling gas molecule, carbon monoxide (CO) has a crucial impact on various physiological and pathological processes in organisms, particularly in oxidative stress processes. Hence, designing and synthesizing a fluorescent probe that can effectively image CO in vivo holds immense significance. In this work, under the guidance of density functional theory (DFT) and time-dependent density functional theory (TDDFT), we designed and synthesized a red aggregation-induced emission (AIE) fluorescent probe THBTA-CO for CO detection and imaging. The fluorescent probe displayed green fluorescence emission at 535 nm before the CO response. However, upon CO response, with the involvement of Pd2+, the probe emitted red fluorescence at 630 nm. Furthermore, we successfully demonstrated the potential of THBTA-CO in visualizing both exogenous and endogenous CO in living cells. Significantly, THBTA-CO was effectively employed to image CO in lipopolysaccharide (LPS)-induced oxidative stress in mice. These findings convincingly establish THBTA-CO as a promising fluorescent probe for CO sensing and imaging, thereby facilitating a better understanding of CO's role in biomedical research.

Common xanthene fluorescent dyes are visible-light activatable CO-releasing molecules.

Fluorescein, eosin Y, and rose bengal are dyes used in clinical medicine and considered (photo-)chemically stable. Upon extensive irradiation with visible light in aqueous solutions, we found that these compounds release carbon monoxide (CO) - a bioactive gasotransmitter - in 40-100% yields along with the production of low-mass secondary photoproducts, such as phthalic and formic acids, in a multistep degradation process. Such photochemistry should be considered in applications of these dyes, and they could also be utilized as visible-light activatable CO-releasing molecules (photoCORMs) with biological implications.

Studying manganese carbonyl photochemistry in a permanently porous metal-organic framework.

Mn(diimine)(CO)3X (X = halide) complexes are critical components of chromophores, photo- and electrocatalysts, and photoactive CO-releasing molecules (photoCORMs). While these entities have been incorporated into metal-organic frameworks (MOFs), a detailed understanding of the photochemical and chemical processes that occur in a permanently porous support is lacking. Here we site-isolate and study the photochemistry of a Mn(diimine)(CO)3Br moiety anchored within a permanently porous MOF support, allowing for not only the photo-liberation of CO from the metal but also its escape from the MOF crystals. In addition, the high crystallinity and structural flexibility of the MOF allows crystallographic snapshots of the photolysis products to be obtained. We report these photo-crystallographic studies in the presence of coordinating solvents, THF and acetonitrile, showing the changing coordination environment of the Mn species as CO loss proceeds. Using time resolved experiments, we report complementary spectroscopic studies of the photolysis chemistry and characterize the final photolysis product as a possible Mn(ii) entity. These studies inform the chemistry that occurs in MOF-based photoCORMs and where these moieties are employed as catalysts.

Water-Soluble Carbon Monoxide-Releasing Molecules (CORMs)

Carbon monoxide-releasing molecules (CORMs) are promising candidates for producing carbon monoxide in the mammalian body for therapeutic purposes. At higher concentrations, CO has a harmful effect on the mammalian organism. However, lower doses at a controlled rate can provide cellular signaling for mandatory pharmacokinetic and pathological activities. To date, exploring the therapeutic implications of CO dose as a prodrug has attracted much attention due to its therapeutic significance. There are two different methods of CO insertion, i.e., indirect and direct exogenous insertion. Indirect exogenous insertion of CO suggests an advantage of reduced toxicity over direct exogenous insertion. For indirect exogenous insertion, researchers are facing the issue of tissue selectivity. To solve this issue, developers have considered the newly produced CORMs. Herein, metal carbonyl complexes (MCCs) are covalently linked with CO molecules to produce different CORMs such as CORM-1, CORM-2, and CORM-3, etc. All these CORMs required exogenous CO insertion to achieve the therapeutic targets at the optimized rate under peculiar conditions or/and triggering. Meanwhile, the metal residue was generated from i-CORMs, which can propagate toxicity. Herein, we explain CO administration, water-soluble CORMs, tissue accumulation, and cytotoxicity of depleted CORMs and the kinetic profile of CO release.