Axial Sites Research Articles

Impact of Adding Distal Forearm Bone Mineral Density Measurement to Axial Bone Mineral Density Measurement for the Diagnosis of Osteoporosis: Prevalence and Risk Factors for Diagnostic Discordance

Background: Studies have demonstrated the superiority of distal forearm bone mineral density (BMD) measurement over axial BMD measurement for prediction of osteoporotic fractures of distal radius. However, distal forearm BMD measurement is not routinely performed at most centers. Objective: To demonstrate the prevalence of discordance in diagnosis of osteoporosis using axial and distal forearm BMD measurement, and to assess whether age and other potential risk factors can predict major discordance. Materials and Methods: Postmenopausal women aged 45 years or older and men aged 50 years or older who underwent lumbar spine, hip, and distal forearm BMD measurement at Prompt Health Center, Faculty of Associated Medical Sciences, Chiang Mai University, Thailand, between January 2021 and December 2021 were recruited. The T-scores of axial site and distal forearm were categorized based on World Health Organization classification to determine the prevalence of diagnostic discordance. Major discordance was defined as having one osteoporotic and one normal T-score. Factors potentially associated with major discordance were explored using univariate and multivariate logistic regression models. Results: Eight hundred eighty-one participants including 621 women and 260 men with a mean age of 59.2±6.7 years were analyzed. There were 13.2% participants diagnosed with osteoporosis of the axial site, and 16.0% of the one-third (1/3) radius. The rates of major discordance, minor discordance, and concordance between axial and 1/3 radius T-scores were 3.2%, 40.5%, and 56.3%, respectively. Age of 65 years or older was significantly associated with major axial and 1/3 radius T-score discordance, with an adjusted odds ratio of 2.7 and 95% confidence interval 1.24 to 5.87 (p=0.012). Conclusion: Diagnostic discordance is observed for at least one-third of the participants using axial and distal forearm BMD measurement. The age of 65 years or older is a risk factor for major discordance. Keywords: Bone mineral density; Osteoporosis; Spine; Hip; Distal forearm; Discordance

Dual photoresponsive & water-triggered nitric oxide releasing materials based on rhodium-based metal-organic polyhedra.

The exogenous administration of nitric oxide (NO) is considered a potential therapeutic treatment against a great variety of diseases due to its significant role in multiple physiological functions. Due to the gaseous nature, short lifetime and dose- and tissue-dependent activity of this molecule, the development of new administration procedures is required to control the NO delivery in terms of dosage, timing, and location. In this work, we propose a new molecular material based on robust metal-organic polyhedra (MOPs) for controlled NO release. We select dirhodium paddlewheel complex-based cuboctahedral MOPs (RhMOP), in which NO can chemically coordinate to the open-metal sites at the axial sites of dirhodium paddlewheel moieties. We further prepare amorphous coordination polymer particles (CPPs) by connecting RhMOP with bis(imidazole) linkers at the external axial sites. Both molecular MOPs and polymeric CPPs show relevant NO payloads and the release of NO can be triggered by two different stimuli: light and humidity. We show that imidazole ligands coordinating to the external axial sites of the paddlewheel moieties tune the light-triggered NO release property. We further demonstrate that the size and the extrinsic pores of CPPs are important for enhanced NO release.

Multi-functional biotinylated platinum(IV)-SAHA conjugate for tumor-targeted chemotherapy.

The development of multi-functional Pt(IV) complexes as chemotherapeutic agents has gained growing attention in medical oncology. However, the design of multi-functional tumor-targeted Pt(IV) complexes with high hydrolytic stability remains challenging. Herein, we have developed a Pt(IV) prodrug conjugated with vorinostat as a multi-functional cancer therapeutic. In this design, the octahedral Pt(IV) prodrug of a DNA damaging anticancer drug cisplatin is tethered to the cancer cell targeting biotin ligand through one of the axial sites and the other axial site of the Pt(IV) center is attached to the anticancer drug vorinostat (also known as SAHA), a histone deacetylase inhibitor (HDACi) approved by the Food and Drug Administration (FDA) for treatment of cutaneous T-cell lymphoma. The designed biotinylated Pt(iv)-SAHA (Biotin-Pt(iv)-SAHA) conjugate is hydrolytically stable but reduced to Pt(II) species under intracellularly relevant conditions and concomitantly releases cisplatin and two of its axial ligands such as SAHA and biotin. The anticancer activity of the conjugate is investigated against a panel of cisplatin-sensitive human cancer cells, including cisplatin-resistant cells. Interestingly, the conjugate exhibited significantly higher cytotoxicity than the clinically approved anticancer drug cisplatin and slightly more cytotoxicity than the HDACi SAHA in all the tested cell lines. By combining the Pt(IV) prodrug of cisplatin with SAHA in the conjugate, synergistic cytotoxicity is achieved. The imaging studies revealed that the conjugate is taken up by cancer cells and shows dose-dependent cell death. The studies on our designed multi-pronged conjugate can be further optimized to enhance its efficacy, paving the way for developing a new class of clinically relevant chemotherapeutic agents.

Peroxymonosulfate activation by trace iron(III) porphyrin for facile degradation of organic pollutants via nonradical oxidation

Nonradical species with great resistance to interference have shown great advantages in complex wastewater treatment. Herein, a novel system constructed by biodegradable tetrakis-(4-carboxyphenyl)-porphyrinatoiron(III) (FeIII-TCPP) and peroxymonosulfate (PMS) was proposed for facile decontamination. Nonradical pathway is observed in FeIII-TCPP/PMS, where 1O2 and high-valent iron-oxo species play dominant roles. The genres and valence of high-valent iron-oxo species, including iron(IV)-oxo porphyrin radical-cationic species [OFeIV-TCPP•+] and iron(IV)-hydroxide species [FeIV-TCPP(OH)], are ascertained, along with their generation mechanism. The axial ligand on the iron axial site affects the ground spin state of FeIII-TCPP, further influencing the thermodynamic reaction pathway of active species. With trace catalyst in micromoles, FeIII-TCPP exhibits high efficiency by degrading bisphenol S (BPS) completely within 5 min, while Co2+/PMS can only achieve a maximum of 26.2% under identical condition. Beneficial from nonradical pathways, FeIII-TCPP/PMS demonstrates a wide pH range of 3–10 and exhibits minimal sensitivity to interference of concomitant materials. BPS is primarily eliminated through β-scission and hydroxylation. Specifically, 1O2 electrophilically attacks the C–S bond of BPS, while high-valent iron-oxo species interacts with BPS through an oxygen-bound mechanism. This study provides novel insights into efficient activation of PMS by iron porphyrin, enabling the removal of refractory pollutants through nonradical pathway.

Reversible Reactions of Nitric Oxide with a Binuclear Iron(III) Nitrophorin Mimic.

Construction of functional synthetic systems that can reversibly bind and transport the most biologically important gaseous molecules, oxygen and nitric oxide (NO), remains a contemporary challenge. Myoglobin and nitrophorin perform these respective tasks employing a protein-embedded heme center where one axial iron site is occupied by a histidine residue and the other is available for small molecule ligation, structural features that are extremely difficult to mimic in protein-free environments. Indeed, the hitherto reported designs rely on sophisticated multistep syntheses for limiting access to one of the two axial coordination sites in small molecules. We have shown previously that binuclear Ga(III) and Al(III) corroles have available axial sites, and now report a redox-active binuclear Fe(III) corrole, (1-Fe)2 , in which each (corrolato)Fe(III) center is 5-coordinate, with one axial site occupied by an imidazole from the other corrole. The binuclear structure is further stabilized by attractive forces between the corrole π systems. Reaction of NO with (1-Fe)2 affords mononuclear iron nitrosyls, and of functional relevance, the reaction is reversible: nitric oxide is released upon purging the nitrosyls with inert gases, thereby restoring (1-Fe)2 in solutions or films.

Crystal structures and properties of Fe(H2O)2[Ni(CN)4]·nH2O hydrates

We report the crystal structures and properties of iron hydrate compounds. These hydrates have 2D topologies and crystallize with three different structural features depending on the number of weakly bonded water molecules. Coordinated water molecules occupy the axial sites of the iron ion and support a network of hydrogen-bonded water molecules in the interlayer region. Crystal structures of these hydrates are known for Mn, Co, and Ni but not for Fe. The structure for the solids considered herein was solved and refined from powder XRD patterns complemented by IR, UV/Vis-NIR, Mössbauer, and TG data. The relevance of this structural study is related to the application of Hofmann-like coordination polymers as spin-crossover materials when the coordinated water molecules are replaced by dipyridines, pyridine, and derivatives that form pillars between adjacent layers. Upon dehydration of these solids, a reactive material is formed by assembly of tetrahedral iron ions with square planar nickel ions.

Post‐Synthetic Modification of Aerogels Made of Covalent Cross‐linked Metal‐Organic Polyhedra

AbstractAerogels are porous ultralight materials known for their high porosity, wide range of pore sizes, low density, and good macroscopic mechanical properties, all of which make them promising candidates for shaped adsorbents, catalysts, and insulators, among other applications. Here, this work reports a new approach that enables both the formation of modular aerogels, via dynamic covalent chemistry, and their post‐synthetic modification, via coordination chemistry. To demonstrate this strategy, this work first polymerizes porous amino‐functionalized Rh(II)‐based metal‐organic polyhedra (MOPs) with aldehydes, which afforded robust imine‐gel networks that is then converted into aerogels. Next, this work functionalizes these aerogels through the coordination of ligands on the axial site of Rh(II) paddlewheels of the MOP. Interestingly, in this chemistry, the local changes in the coordination site of the MOPs are transferred to the overall aerogel, thereby altering its macroscopic physicochemical properties. Importantly, this feature enables the synthesis of optimized adsorbents tailored to specific guests, as this work demonstrates through a series of experiments using ligands of different electrostatic and hydrophobic characters.

Selective Radical Transfer in a Series of Nonheme Iron(III) Complexes.

A series of nonheme iron complexes, FeIII(BNPAPh2O)(Lax)(Leq) (Lax/eq = N3-, NCS-, NCO-, and Cl-) have been synthesized using the previously reported BNPAPh2O- ligand. The ferrous analogs FeII(BNPAPh2O)(Lax) (Lax = N3-, NCS-, and NCO-) were also prepared. The complexes were structurally characterized using single crystal X-ray diffraction, which shows that all the FeIII complexes are six-coordinate, with one anionic ligand (Lax) in the H-bonding axial site and the other anionic ligand (Leq) in the equatorial plane, cis to the Lax ligand. The reaction of FeIII(BNPAPh2O-)(Lax)(Leq) with Ph3C• shows that one ligand is selectively transferred in each case. A selectivity trend emerges that shows •N3 is the most favored for transfer in each case to the carbon radical, whereas Cl• is the least favored. The NCO and NCS ligands showed an intermediate propensity for radical transfer, with NCS > NCO. The overall order of selectivity is N3 > NCS > NCO > Cl. In addition, we also demonstrated that H-bonding has a small effect on governing product selectivity by using a non-H-bonded ligand (DPAPh2O-). This study demonstrates the inherent radical transfer selectivity of nonhydroxo-ligated nonheme iron(III) complexes, which could be useful for efforts in synthetic and (bio)catalytic C-H functionalization.

A Case Showing a New Diagnostic Aspect of the Application of Radiofrequency Echographic Multi-Spectrometry (REMS).

Radiofrequency echographic multi-spectrometry (REMS) is an ultrasound technique that has been recently introduced in the medical field to detect osteoporosis and fracture risk at axial sites. The use of sonography to visualize the region of interest (ROI) of the hip neck provides the opportunity to identify occult fractures. A 91-year-old woman with persistent right leg pain was referred to rheumatologist due to a known history of arthritis and osteoporosis. She was able to walk using a crutch, although experiencing an antalgic gait. The patient had recently fallen on her right side from standing height. During the visualization of the ROI of the right femoral neck using REMS, an abrupt break of the femoral cortex suspected to be a fracture was seen; therefore, the measurement of the femoral neck was performed on the left side. The T-score had value of -2.9 SD and the fragility score was 86.7. Due to unclear signs of a fracture after an X-ray of the hip, a computed tomography (CT) exam of the hip was performed, which revealed a femoral neck fracture. Occult fractures of the femoral neck are challenging to diagnose and require numerous radiologic exams. The use of ultrasound as a method to measure bone density allows the simultaneous diagnosis of osteoporosis and detection of fractures.

Heteroleptic dirhodium(II,II) acetato-bipyridyl complexes: Evaluation as catalyst precursors for hydroformylation reactions

The synthesis of cationic bimetallic ‘pseudo-paddlewheel’ dirhodium(II,II) acetato-bipyridyl complexes of the type [Rh2(OAc)2(bis-4,4′-R-bipy)2]2+ containing either acetate (AcO-) or hexafluorophosphate (PF6-) counter ions is described. In both series, the 4 and 4′ positions of each bipyridyl ligand are substituted such that R = H, CF3 or OMe (complexes 1-3 for AcO- and 4-6 for PF6- derivatives). As catalyst precursors for the hydroformylation reaction, the complexes were initially evaluated using 1-octene as a substrate. The complex which displayed the greatest chemoselectivity toward aldehydes was evaluated further as a catalyst precursor for the hydroformylation of styrene, cyclohexene and 7-tetradecene as substrates. A correlation between product distributions in terms of chemo- and regioselectivity in the hydroformylation reaction versus axial site interaction is delineated. Recyclability was achieved through suitable modification of the substituent and counter ion, culminating in a simplistic method of post-catalytic precursor collection with minimal reduction of the catalytic activity over 5 cycles.

Synthesis, crystal structure, stereochemical and Hirshfeld surface analysis of trans-di-aqua-bis-(1-phenyl-propane-1,2-di-amine-κ2N,N')nickel(II) dichloride dihydrate.

In the hydrated complex salt, [Ni(C9H14N2)2(H2O)2]Cl2·2H2O, the asymmetric unit comprises of half of the complex cation along with one chloride anion and one non-coordinating water mol-ecule. The central nickel(II) atom is located on an inversion center and is coordinated in a trans octa-hedral fashion by four N atoms from two bidentate 1,2-di-amino-1-phenyl-propane ligands in the equatorial plane, and by two oxygen atoms from two water mol-ecules occupying the axial sites. The five-membered chelate ring is in a slightly twisted envelope conformation. The crystal packing features O-H⋯Cl, N-H⋯O and N-H⋯Cl hydrogen bonds. Hirshfeld surface analysis revealed that the most important contributions to the crystal packing are from H⋯H (56.4%), O⋯H/H⋯O (16.4%) and H⋯Cl (13.3%) inter-actions. The crystal void volume was calculated to be 15.17%.

Synthesis and crystal structure of bis-(tert-butyl isocyanide-κC)[5,10,15,20-tetra-kis-(4-chloro-phen-yl)porphyrinato-κ4N]iron(II).

In the title compound, [FeII(C44H24Cl4N4)(C5H9N)2] or [FeII(TClPP)(t-BuNC)2] [where TClPP and t-BuNC are 5,10,15,20-tetra-kis-(4-chloro-phen-yl)porphyrinate and tert-butyl isocyanide ligands, respectively], the metal ion lies on an inversion center and is octa-hedrally coordinated by the N atoms of the porphyrin ring in the equatorial plane and by carbon atoms of the trans t-BuNC ligands in the axial sites. The Fe-N bond length of 2.0074 (14) Å suggests a low-spin complex (S = 0). The crystal packing of the title compound is sustained by C-H⋯Cl, C-H⋯N and C__H⋯Cg (Cg = the centroid of a pyrrole ring of the TClPP porphyrinate) inter-actions, leading to a three-dimensional network. The Hirshfeld surface (HS) analysis indicates that 61.4% of the inter-molecular inter-actions are from H⋯H contacts while other contributions are from C⋯H/H⋯C, O⋯H/H⋯O and N⋯H/H⋯N inter-actions, which comprise 21.3%, 13.3% and 3.6% of the HS, respectively.

A Different Perspective on Tuning the Photophysical and Photochemical Properties: The Influence of Constitutional Isomers in Group 6 Carbonyl Complexes with Pyridyl-Mesoionic Carbenes.

Exploring novel and existing design principles to tune the photochemical and photophysical properties of transition-metal complexes is an important goal in contemporary research. Here, we highlight the influence of constitutional isomers of pyridyl-1,2,3-triazolylidene mesoionic carbene (MIC) ligands on the photophysical and photochemical properties of the corresponding tetracarbonyl group 6 metal complexes (M = Cr, Mo, W). All new complexes [M(C-C)] presented herein incorporate a C-C linked pyridyl-MIC ligand and were fully characterized by X-ray diffraction analysis, elemental analysis, and 1H NMR and IR spectroscopy. Detailed photophysical investigations reveal a single emission in the VIS region, which extends into the NIR with lifetimes of up to 3.5 μs in the solid state at lower temperatures. The quantum yields were determined for all three complexes, and, in particular, the W0 complex shows an unusually high quantum yield of 29% compared to the values of 0.02% obtained for the [M(C-N)] isomers investigated in earlier works. Beyond this, the investigated W0 complex also exhibits an emission at 717 nm in a fluid solution. The combination of luminescence and FTIR-step scan spectroscopy with theoretical calculations reveals an emissive 3MLCT state. Irradiation of the presented complexes leads to a clean cleavage of one axial CO ligand. A metastable 16 VE species with a vacant axial coordination site was detected in the solid state at low temperatures. In solution, the respective solvato complexes are formed. A dark reverse reaction is observed, as previously described for the [M(C-N)] analogues. The increased electron density induced by the C-C linked pyridyl-MIC ligand leads to an increased kinetic rate constant for the reformation of the starting species and is also reflected in the lower photodissociation quantum yields.

Precise Design and Modification Engineering of Single-Atom Catalytic Materials for Oxygen Reduction.

Due to their unique electronic and structural properties, single-atom catalytic materials (SACMs) hold great promise for the oxygen reduction reaction (ORR). Coordinating environmental and engineering strategies is the key to improving the ORR performance of SACMs. This review summarizes the latest research progress and breakthroughs of SACMs in the field of ORR catalysis. First, the research progress on the catalytic mechanism of SACMs acting on ORR is reviewed, including the latest research results on the origin of SACMs activity and the analysis of pre-adsorption mechanism. The study of the pre-adsorption mechanism is an important breakthrough direction to explore the origin of the high activity of SACMs and the practical and theoretical understanding of the catalytic process. Precise coordination environment modification, including in-plane, axial, and adjacent site modifications, can enhance the intrinsic catalytic activity of SACMs and promote the ORR process. Additionally, several engineering strategies are discussed, including multiple SACMs, high loading, and atomic site confinement. Multiple SACMs synergistically enhance catalytic activity and selectivity, while high loading can provide more active sites for catalytic reactions. Overall, this review provides important insights into the design of advanced catalysts for ORR.

New Insights into Pathogenesis, Diagnosis and Treatment of Psoriatic Arthritis

Introduction: Psoriatic Arthritis (PSA) is an inflammatory musculoskeletal disorder characterized by significant dysfunction in synovial tissue, tendons and axial sites. PSA is associated with metabolic comorbidities such as diabetes, obesity, congestive heart failure, fatty liver disease, depression and/or anxiety. Due to differences in the clinical manifestations of PSA, some patients are not diagnosed through clinical examination. Delayed psoriatic arthritis diagnosis or consultation has been related to low quality of life and increased frequency of comorbidities and persistent inflammatory state. The aim of the present study was to explore multiple etiologies of PSA, screening tools, and pharmaceutical therapy. Articles were searched from international databases including Magiran, Scopus, Google Scholar, PubMed, and Springer. The keywords of Psoriatic Arthritis, Screening tools, pathogenesis, treatment, and Biomarkers were used to extract articles.
 Conclusion: Our study showed that heterogeneity in the etiology of PSA was a major reason for classification problems within this disease spectrum. The explanation for this disease heterogeneity may be focused on variations in genetic and environmental factors. Screening strategies (ex: CASPAR criteria and biomarkers) are a significant first step in early treatment. Moreover, many types of therapy are available to help decreased joint problems, muscle weakness, and disease severity. Detection of dependent factors related to PSA might help in the early intervention of these patients to address clinical and para-clinical issues.
 Here we have provided an updated review of the early diagnosis, clinical features, pathogenesis, screening tools, biomarkers, and treatment recommendations, such as new biologic medications, for Psoriatic Arthritis.

Coordination Tuning of Metal Porphyrins for Improved Oxygen Evolution Reaction.

The nucleophilic attack of water or hydroxide on metal-oxo units forms an O-O bond in the oxygen evolution reaction (OER). Coordination tuning to improve this attack is intriguing but has been rarely realized. We herein report on improved OER catalysis by metal porphyrin 1-M (M=Co, Fe) with a coordinatively unsaturated metal ion. We designed and synthesized 1-M by sterically blocking one porphyrin side with a tethered tetraazacyclododecane unit. With this protection, the metal-oxo species generated in OER can maintain an unoccupied trans axial site. Importantly, 1-M displays a higher OER activity in alkaline solutions than analogues lacking such an axial protection by decreasing up to 150-mV overpotential to achieve 10 mA/cm2 current density. Theoretical studies suggest that with an unoccupied trans axial site, the metal-oxo unit becomes more positively charged and thus is more favoured for the hydroxide nucleophilic attack as compared to metal-oxo units bearing trans axial ligands.

Coordination Tuning of Metal Porphyrins for Improved Oxygen Evolution Reaction

AbstractThe nucleophilic attack of water or hydroxide on metal‐oxo units forms an O−O bond in the oxygen evolution reaction (OER). Coordination tuning to improve this attack is intriguing but has been rarely realized. We herein report on improved OER catalysis by metal porphyrin 1‐M (M=Co, Fe) with a coordinatively unsaturated metal ion. We designed and synthesized 1‐M by sterically blocking one porphyrin side with a tethered tetraazacyclododecane unit. With this protection, the metal‐oxo species generated in OER can maintain an unoccupied trans axial site. Importantly, 1‐M displays a higher OER activity in alkaline solutions than analogues lacking such an axial protection by decreasing up to 150‐mV overpotential to achieve 10 mA/cm2 current density. Theoretical studies suggest that with an unoccupied trans axial site, the metal‐oxo unit becomes more positively charged and thus is more favoured for the hydroxide nucleophilic attack as compared to metal‐oxo units bearing trans axial ligands.

Catalytic water oxidation mediated by copper‐triazolylpyridine complexes

Water oxidation reaction (WOR) is a rather sluggish process in the water splitting that hampers the extraction of hydrogen gas from water in a large scale. It is highly desirable to develop low‐cost WOR catalysts to increase the efficacy. Herein two Cu(II) complexes [Cu (DTEL)2]n(ClO4)2n (1) and [Cu(DTE)2(ClO4)2] (2) of two triazolylpyridines, 1‐(2‐hydroxy)‐4‐(2‐pyridyl)1,2,3‐triazole (DTEL) and 1‐(2‐acetoxymethyl)‐4‐(2‐pyridyl)1,2,3‐triazole (DTE), have been synthesized and characterized. The X‐ray diffraction analysis revealed that the copper centers of 1 and 2 adopted the octahedral coordination geometry with four N atoms from two DTEL or DTE ligands in the equatorial plane. The two axial sites were weakly ligated by the hydroxyl group of DTEL or perchlorate. Both complexes 1 and 2 were homogenous molecular catalysts boosting the WOR in pH 9.0 phosphate buffer solution with the overpotentials being 568 and 478 mV, rate constants (kcat) of 0.1 and 0.39 s−1, and Faradaic efficiencies of 90% and 93%, respectively. The pendant substituent on the two triazolylpyridine ligands DTEL and DTE apparently influenced the catalysis. A mechanism for the catalytic WOR mediated by 1 and 2 was suggested on the basis of the experimental data. This work illustrated that triazolylpyridines were promising scaffolds for forming metal complexes working as WOR catalysts.

Coordinatively Unsaturated Metallates of Cobalt(II), Nickel(II), and Zinc(II) Guarded by a Rigid and Narrow Void.

Both natural enzymatic systems and synthetic porous material catalysts utilize well-defined and uniform channels to dictate reaction selectivities on the basis of size or shape. Mimicry of this design element in homogeneous systems is generally difficult owing to the flexibility inherent in most small molecular species. Herein, we report the synthesis of a tripodal ligand scaffold that orients a narrow and rigid cavity atop accessible metal coordination space. The permanent void is formed through a macrocyclization reaction whereby the 3,5-dihydroxyphenyl arms are covalently linked through methylene bridges. Deprotonative metallation leads to anionic and coordinatively unsaturated complexes of divalent cobalt, nickel, and zinc. An analogous series of trigonal monopyramidal complexes bearing a nonmacrocyclized variant of the tripodal ligand are also reported. Physical characterization of the coordination complexes has been carried out using multiple spectroscopic techniques (NMR, EPR, and UV-vis), cyclic voltammetry, and X-ray diffraction. Complexes of the macrocyclized [LOCH2O]3- ligand retain a rigid cavity upon metallation, with this cavity guarding the entrance to the open axial coordination site. Through a combination of spectroscopic and computational studies, it is shown that acetonitrile entry into the void is sterically precluded, disrupting anticipated coordination at the intracavity site.

Multifunctional Iridium(III)-Platinum(IV) Conjugates as Potent Anticancer Theranostic Agents.

In this article, we report IriPlatins 1-3, a new class of heterobimetallic Ir(III)-Pt(IV) conjugates as multifunctional potent anticancer theranostic agents. In the designed construction, the octahedral Pt(IV) prodrug is tethered to the cancer cell targeting biotin ligand through one of the axial sites and the other axial site of Pt(IV) center is attached to multifunctional Ir(III) complexes that possess organelle-targeting capabilities with excellent anticancer and imaging properties. The conjugates preferentially accumulate within the mitochondria of cancer cells, and subsequently, Pt(IV) is reduced to Pt(II) species that concomitantly releases both the Ir(III) complex and biotin from its axial sites. The IriPlatin conjugates demonstrate potent anticancer activity in various 2D monolayer cancer cells, including the cisplatin-resistant cells in the nanomolar concentrations and 3D multicellular tumor spheroids. The mechanistic investigation of conjugates suggests that the loss of MMP, generation of ROS, and caspase-3-mediated apoptosis are responsible for cell death.