BODIPY based Metal-Organic Macrocycles and Frameworks: Recent Therapeutic Developments.

Boron dipyrromethene, commonly known as BODIPY, based metal-organic macrocycles (MOCs) and metal-organic frameworks (MOFs) represent an interesting part of materials due to their versatile tunability of structure and functionality as well as significant physicochemical properties, thus broadening their applications in various scientific domains, especially in biomedical sciences. With increasing concern over the efficacy of cancer drugs versus quality of patient's life dilemma, scientists have been trying to fabricate novel comprehensive therapeutic strategies along with the discovery of novel safer drugs where research with BODIPY metal complexes has shown vital advancements. In this review, we have exclusively examined the articles involving studies related to light harvesting and photophysical properties of BODIPY based MOCs and MOFs, synthesized through self-assembly process, with a special focus on biomolecular interaction and its importance in anti-cancer drug research. In the end, we also emphasized the possible practical challenges involved during the synthetic process, based on our experience on dealing with BODIPY molecules and steps to overcome them along with their future potentials. This review will significantly help our fellow research groups, especially the budding researchers, to quickly and comprehensively get the near to wholesome picture of BODIPY based MOCs and MOFs and their present status in anti-cancer drug discovery.

Patient blood management in India - Review of current practices and feasibility of applying appropriate standard of care guidelines. A position paper by an interdisciplinary expert group.

In a developing country like India, with limited resources and access to healthcare facilities, dealing with massive hemorrhage is a major challenge. This challenge gets compounded by pre-existing anemia, hemostatic disorders, and logistic issues of timely transfer of such patients from peripheral hospitals to centers with adequate resources and management expertise. Despite the awareness amongst healthcare providers regarding management modalities of bleeding patients, no uniform Patient Blood Management (PBM) or perioperative bleeding management protocols have been implemented in India, yet. In light of this, an interdisciplinary expert group came together, comprising of experts working in transfusion medicine, hematology, obstetrics, anesthesiology and intensive care, to review current practices in management of bleeding in Indian healthcare institutions and evaluating the feasibility of implementing uniform PBM guidelines. The specific intent was to perform a gap analysis between the ideal and the current status in terms of practices and resources. The expert group identified interdisciplinary education in PBM and bleeding management, bleeding history, viscoelastic and platelet function testing, and the implementation of validated, setting-specific bleeding management protocols (algorithms) as important tools in PBM and perioperative bleeding management. Here, trauma, major surgery, postpartum hemorrhage, cardiac and liver surgery are the most common clinical settings associated with massive blood loss. Accordingly, PBM should be implemented as a multidisciplinary and practically applicable concept in India in a timely manner in order to optimize the use the precious resource blood and to increase patients' safety.

Enhanced Photocatalytic Performance of Nanosized Mixed-Ligand Metal-Organic Frameworks through Sequential Energy and Electron Transfer Process.

Effective sequestration of harmful organic pollutants from wastewater has been a persistent concern in the interest of environmental and ecological protection from pollution and hazards. Currently, common water treatment technologies such as adsorption, coagulation, and membranes are expensive and not greatly effective. A new class of organic and inorganic composite metal-organic frameworks (MOFs) has emerged as an essential class of materials for numerous applications, including photocatalytic degradation of organic pollutants. Herein, we present a nanosize mixed-ligand MOF (nMLM) which was successfully synthesized by reacting a Zr metal source with a mixture of pyrene and porphyrin building units and further utilized as photocatalyst in the photodegradation of rhodamine B (RhB). The nMLM MOF showed excellent photocatalytic efficiency, which was due to the complementary absorption and sequential energy and electron transfer properties of its building blocks, pyrene and porphyrin. We also propose herein a possible mechanism of the photocatalytic function of the material.

Mitochondrial Localization of Highly Fluorescent and Photostable BODIPY-Based Ruthenium(II), Rhodium(III), and Iridium(III) Metal Complexes.

A new N,O-based BODIPY ligand was synthesized and further utilized to develop highly fluorescent and photostable Ru(II), Rh(III), and Ir(III) metal complexes. The complexes were fully characterized by different analytical techniques including single-crystal XRD studies. The photostabilities and live cell imaging capabilities of the complexes were investigated via confocal microscopy. The complexes localized specifically in the mitochondria of live cells and showed negligible cytotoxicities at a concentration used for imaging purposes. They also exhibited high photostabilities, with fluorescence intensities remaining above 50% after 1800 scans.

In Vitro Mechanistic Study of the Anti-inflammatory Activity of a Quinoline Isolated from Spondias pinnata Bark.

The search for new plant-based anti-inflammatory drugs continues in order to overcome the detrimental side effects of conventional anti-inflammatory agents, both steroidal and nonsteroidal. This study involves the quinoline SPE2, 7-hydroxy-6-methoxyquinolin-2(1 H)-one, isolated from the EtOAc fraction of Spondias pinnata bark. Structure elucidation was done using analytical spectroscopic methods including Fourier transform infrared spectroscopy, high-resolution electrospray ionization mass spectrometry, nuclear magnetic resonance spectroscopy, and single-crystal X-ray crystallography. The anti-inflammatory activity of SPE2 was evaluated in a lipopolysaccharide (LPS)-stimulated murine macrophage RAW 264.7 model. SPE2 effectively suppressed LPS-induced overproduction of pro-inflammatory mediators such as nitric oxide (NO), tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß, and reactive oxygen species. Expression levels of NO synthesizing enzyme, cyclooxygenase-2, TNF-α, IL-6 and IL-1ß were also determined to return to normal after SPE2 treatment. Localization of NF-κB was evaluated by confocal microscopy and Western blotting, which showed a dose-dependent reduction of NF-κB inside the nucleus and an increase in cytoplasmic NF-κB with SPE2 treatment. Collectively, the results suggest that SPE2 has anti-inflammatory activity via inhibition of NF-κB activation.

Self-Assembly of Novel Thiophene-Based BODIPY RuII Rectangles: Potential Antiproliferative Agents Selective Against Cancer Cells.

Novel Ru (2+2) rectangles were designed and synthesized by self-assembly of a new thiophene-functionalized dipyridyl BODIPY ligand, BDPS, and ruthenium(II) precursors. The complexes exhibited dose-dependent antiproliferative activities against cancer cells, in which some compounds selectively kill cancer cells. The net fluorescence due to BODIPY allowed us to visualize their location inside cancer cells. Moreover, the metalla-rectangles displayed substantial propensity to bind with biomolecules.

Self-Assembled Novel BODIPY-Based Palladium Supramolecules and Their Cellular Localization.

Four new palladium metal supramolecules with triangular/square architectures derived from boron dipyrromethane (BODIPY) ligands were synthesized by self-assembly and fully characterized by 1H and 31P NMR, electrospray ionization mass spectrometry, and single-crystal X-ray diffraction. These supramolecules were more cytotoxic to brain cancer (glioblastoma) cells than to normal lung fibroblasts. Their cytotoxicity to the glioblastoma cells was higher than that of a benchmark metal-based chemotherapy drug, cisplatin. The characteristic green fluorescence of the BODIPY ligands in these supramolecules permitted their intracellular visualization using confocal microscopy, and the compounds were localized in the cytoplasm and on the plasma membrane.

Exploiting natural products to build metalla-assemblies: the anticancer activity of embelin-derived Rh(III) and Ir(III) metalla-rectangles.

Six new pentamethylcyclopentadienyl Rh(III) and Ir(III) metalla-rectangles ([3](CF3SO3)4-[8](CF3SO3)4) have been prepared by a self-assembly strategy using the embelin-derived metalla-clips (η5-C5Me5)2M2(µ4-C6HRO4-κO)Cl2 (M = Rh, 1; M = Ir, 2; R = (CH2)10CH3) and the linear ditopic ligands, pyrazine, 4,4'-bipyridine and 1,2-bis (4-pyridyl)ethylene. These new metalla-rectangles have been obtained in high yield and isolated as their triflate salts. The complexes have been fully characterized by standard spectroscopic techniques and the antiproliferative activity of these tetranuclear complexes was evaluated in vitro on cancerous (DU-145, A-549, HeLa) and noncancerous (HEK-293) cell lines. The biological study has showed a better activity for the rhodium derivatives over the iridium analogs and for all complexes a very good selectivity for cancerous over noncancerous cells. The presence of lipophilic side chains coupled with the positive charge of the tetranuclear complexes suggested a cytotoxic activity involving the mitochondrial machinery, as demonstrated by multiple biological experiments.

A mixed-ligand Co metal-organic framework and its carbon composites as excellent electrocatalysts for the oxygen evolution reaction in green-energy devices.

Oxygen evolution reaction (OER) electrocatalysts are frequently made from noble metal-based oxides like ruthenium/iridium oxides. However, because of their scarcity and high price, researchers are now focusing on creating innovative OER catalysts based on affordable transition metals that have improved electrical conductivity and accessibility to active sites. Metal-organic frameworks (MOFs), a unique class of inorganic materials with excellent physical and chemical properties, have witnessed significant progress in promising green energy systems. In this work, a novel mixed-ligand metal-organic framework [Co(µ-1κN,2κN'-BDP)(µ3-1κoo',2κo''2κo'''-BTC)]n·nH2O (BDP = boron-dipyrromethene or BODIPY; BTC = benzene tricarboxylate) denoted as CoBDPMOF has been synthesized, and its composites with different carbon materials have been designed. Compared to the pristine MOF, the composites showed enhanced electrocatalytic activity toward the oxygen evolution reaction (OER) in alkaline media. In addition, the CoBDPMOF with activated carbon showed the highest OER performance with a low Tafel slope (82 mV dec-1) and the highest j600 (59.8 mA cm-2), outperforming noble metal IrO2, the OER benchmark electrocatalyst. This study presents new insights into the design and application of CoBDPMOF-based materials for energy conversion and suggests promising avenues for further research and development in electrocatalysis.

Leveraging Resource Centers for Strengthening Immunization Supply Chain.

The efficacy of immunization programs is critically dependent on robust supply chain management, a complex challenge exacerbated by expanding program scopes and evolving vaccine technologies. This comprehensive review underscores the pivotal role of Resource Centers in fortifying the immunization supply chain, presenting a paradigm shift toward enhanced national and global health outcomes. Through a detailed examination of their key activities, the article elucidates how these centers catalyze improvements across various facets of supply chain management - from the integration of suitable technology technologies and specialized training programs to the development of sustainable models and advocacy for policy prioritization. This further explores the multifaceted challenges these centers confront, including funding constraints, capacity building, and infrastructural gaps, alongside the burgeoning opportunities presented by new vaccine introductions, donor interest in health system strengthening, and the potential for broadened scope beyond immunization. By weaving together examples of existing centers worldwide, the review highlights their contributions towards optimizing vaccine logistics, enhancing data management, and ultimately achieving Sustainable Development Goal 3. The insights provided offer valuable guidance for planning and sustaining resource centers, positioning them as indispensable allies in the global pursuit of universal immunization coverage.

Biological studies of chalcogenolato-bridged dinuclear half-sandwich complexes.

A series of cationic chalcogenolato-bridged diruthenium complexes [(η(6)-p-MeC6H4Pr(i))2Ru2(µ-EC6H5)3](+) (E = S, 1; E = Se, 2; E = Te, 3) has been obtained in ethanol from the reaction of (η(6)-p-MeC6H4Pr(i))2Ru2(µ-Cl)2Cl2 with benzenethiol, benzeneselenol, and sodium tellurophenolate, respectively. The thiolato and selenolato derivatives are isolated in good yield as the chloride salts, while the tellurolato analogue is isolated as the hexafluorophosphate salt. Similarly, the dinuclear pentamethylcyclopentadienyl (C5Me5) rhodium and iridium complexes (η(5)-C5Me5)2M2(µ-Cl)2Cl2 react with benzenethiol, benzeneselenol, and sodium tellurophenolate in ethanol to give the corresponding cationic dinuclear complexes of the general formula [(η(5)-C5Me5)2M2(µ-EC6H5)3](+) (M = Rh, E = S, 4; E = Se, 5; E = Te, 6; M = Ir, E = S, 7; E = Se, 8; E = Te, 9). In addition, cationic dinuclear complexes with mixed thiolato-selenolato and thiolato-tellurolato bridges have been prepared, [(η(6)-p-MeC6H4Pr(i))2Ru2(µ-EC6H5)(µ-SCH2C6H4-p-Bu(t))2](+) (E = Se, 10; E = Te, 11) and [(η(5)-C5Me5)2M2(µ-EC6H5)(µ-SCH2C6H5)2](+) (M = Rh, E = Se, 12; E = Te, 13; M = Ir, E = Se, 14; E = Te, 15), starting from the neutral dinuclear complexes (η(6)-p-MeC6H4Pr(i))2Ru2Cl2(µ-SCH2C6H4-p-Bu(t))2 and (η(5)-C5Me5)2M2Cl2(µ-SCH2C6H5)2. All complexes are highly cytotoxic showing activity in the submicromolar range. The nature of the chalcogenolato bridges seems to have an impact on the activity, while the nature of the metal center plays a minor role. Among the complexes tested, the dinuclear complexes 1, 4, and 7 with the thiolato bridges show the highest activity on cancer cells and the best affinity for CT-DNA as demonstrated by cell biology and biophysical experiments.

Pyrene and porphyrin-based Zn metal 1-D-polymer: synthesis, molecular structure, and photocatalytic property.

A zinc-based pyrene-porphyrin hybrid linear 1-D coordination polymer ZnPyrPorp with general formula [Zn(Pyr)(Porp)]n (Pyr = pyrene, Porp = tetraphenylporphyrin) was synthesized using a facile one-pot solvothermal method and fully characterized using different analytical techniques. The single-crystal X-ray diffraction (SCXRD) structure exhibited an interesting morphology with zinc metal coordinated to the porphyrin center, which was further bonded to the pyridine groups of the pyrene ligand, resulting in a linear 1-D-type polymer, with repeated Pyr-ZnTPP-Pyr units. The light-harvesting properties of the ZnPyrPorp polymer were investigated. Additionally, ZnPyrPorp showed excellent catalytic activity toward the photooxidation of 1,5-dihydroxynaphthalene.

[Bis-(2-pyrid-yl-κN)amine]chlorido(η-hexa-methyl-benzene)-ruthenium(II) hexa-fluorido-phosphate dichloro-methane solvate.

In the title half-sandwich complex, [RuCl(η(6)-C(12)H(18))(C(10)H(9)N(3))]PF(6)·CH(2)Cl(2), the ruthenium(II) ion is four-coordinated by a chloro, a hexa-methyl-benzene and a bidentate N,N'-chelating di(pyridin-2-yl)amine ligand. In the crystal, the amino N-H group forms a hydrogen bond with the chloro ligand of a neighbouring complex, thus forming chains along the b axis. Weak inter-molecular C-H⋯F and C-H⋯ Cl contacts are also observed.

Reducing split-thickness skin grafting donor site agony; faster healing and decreased pain-role of platelet-rich plasma.

INTRODUCTION: The split-thickness skin graft harvested donor site is associated with prolonged healing, discomfort, and pain. Platelet-rich plasma (PRP) contains platelet-derived growth factors and has been widely used in chronic wounds and skin graft donor sites. PRP application is known to accelerate wound epithelialization rates, and also reduce postoperative wound site pain. MATERIALS AND METHODS: We assessed 20 patients admitted to our hospital service who underwent split-thickness skin grafting (STSGs) with proximal half of the donor site treated with PRP. The dressing was conducted on postoperative day 7, 14, and 21. The donor site healing was assessed with serial photographs and donor site pain measured by numerical rating scale. RESULTS: Complete healing of wounds (epithelialization) was present in 12 (60%) patients dressed with PRP. Pain on opening dressing was an average of 3.5 in PRP dressed wounds and 6.35 in control wounds. Patients dressed without PRP, none of them had complete epithelialization. All patients had partial healing and were less than the donor site dressed with PRP. Based on these results, skin graft donor site with PRP showed accelerated healing and reduced pain and discomfort compared to control without PRP. CONCLUSION: PRP is a beneficial adjunct for reducing donor site pain and increased healing of donor site following STSG harvest.

Magnitude and causes of routine immunization disruptions during COVID-19 pandemic in developing countries.

The ongoing pandemic of COVID-19 is a threat to various routine healthcare services. India's routine immunization (RI) campaign is one of largest ever known. In this review, we discuss the magnitude of disruption of RI activities due to COVID-19 pandemic, various causes of it and recommend ways to reduce the disruptions. Prominent literature databases were searched till April 30, 2021 for articles reporting disruptions of RI due to COVID-19. One study from India and numerous from outside India reported significant declines in the vaccine coverage rates during the lockdown period, which ranged from March 2020 till August 2020 in different regions of the world. Some reported disruptions for all vaccines, while a few reported sparing of birth doses. Shortage of healthcare workers due for them being diverted to patient care services and their reduced movement due to lockdowns and non-availability of public transport were prominent causes. Parents avoided RI sessions as they feared them or their children getting infected. They also faced travel restrictions, just like the healthcare workers. Children of school entry age and those from poorer socio-demographic profile appeared to miss the doses more frequently. Ministry of Health and Family Welfare, India has issued guidelines for conducting fixed and outreach RI sessions while following COVID-appropriate behavior. Promptly identifying missed out children and scheduling catch-up sessions is required to sustain the gains made over the decades by the immunization program of India.

Heterometallic BODIPY-Based Molecular Squares Obtained by Self-Assembly: Synthesis and Biological Activities.

Metal-based multinuclear supramolecules with different functionalities designed by self-assembly represent a growing area of research due to their versatile applications, particularly as anticancer agents. Four novel boron dipyrromethene (BODIPY)-based octacationic heterometallic molecular squares, 3-6 were synthesized by self-assembly via reaction of dipyridyl BODIPY ligands with suitable 90° palladium and platinum acceptors. The formation of the as-synthesized molecular squares was confirmed by multinuclear NMR spectroscopy, elemental analysis, high resolution electrospray mass spectrometry, UV-vis spectroscopy, and fluorescence spectroscopy. The square molecular structures of 4 and 6 were further rationalized theoretically using the PM7 semi-empirical method. The activities of the supramolecules against cancer cells were tested using cell lines of various malignant and nonmalignant origins. Complexes 3-6 showed high cytotoxicity toward cancer cells but 7.0 to 15.2 times lower cytotoxic effects were observed against nonmalignant human kidney epithelial cells (HEK-293). Particularly, complexes 3-6 provided 2.1-6.0 times lower IC50 values as compared to cisplatin in HCT116 cells. Interestingly, BDP ligand-containing complexes (3 and 4) induced cytotoxicity through apoptosis, whereas BDPCC-based complexes (5 and 6) induced cell death by necrosis. This study presents a novel series of iron-based heteroatomic palladium and platinum complexes that exhibit substantial potential as drug candidates for anticancer therapy.

Self-Assembled BODIPY-Based Iridium Metallarectangles: Cytotoxicity and Propensity to Bind Biomolecules.

A new 4-ethynylpyridine 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY)-based ligand L, which was synthesized by means of the Sonogashira coupling method, was used to obtain two new [2+2] iridium-based metallarectangles, 3 and 4. Ligand L and metallarectangles 3 and 4 were fully characterized through various analytical techniques. The structure of rectangle 4 was further confirmed by single-crystal X-ray diffraction analysis, which showed the formation of an expected [2+2] supramolecule, in which the iridium metal centers were bridged with ligand L to form the desired metallarectangle 4. In the context of the growing biological interest in metallarectangles, rectangle 4 was found to be highly active against two types of cancer cells, with IC50 values almost threefold superior to those of cisplatin. Both 3 and 4 showed dose-dependent abilities to bind bovine serum albumin and salmon sperm DNA; this indicated their tendency to interact with such biomolecules as a potential mode of action.

BODIPY-based Ru(II) and Ir(III) organometallic complexes of avobenzone, a sunscreen material: Potent anticancer agents.

The use of organic compounds with known medicinal properties in the synthesis of metal-based complexes is an important alternative to improve the biological activity of metal-based drugs. The reaction of [M(arene)Cl2]2 (M = Ru, arene = p-cymene and M = Ir, arene = pentamethylcyclopentadienyl, cp*) with avobenzone (1-(4-tert-butylphenyl)-3-(4-methoxyphenyl)propane-1,3-dione, AVBH) and KOH in methanol leads to the formation of the neutral complexes [Ru(p-cymene)(AVB)Cl] 1 and [Ir(cp*)(AVB)Cl] 2 (cp* = pentamethylcyclopentadienyl). Subsequent reaction of 1 and 2 with pyridyl derivative-BODIPY ligands, BDP and BDPCC (BODIPY = boron dipyrromethene, BDP = 4-dipyridine boron dipyrromethene, BDPCC = 4-ethynylpyridine boron dipyrromethene) in methanol gives a series of four new dicationic supramolecules: [Ru2(p-cymene)2(AVB)2BDP][2CF3SO3] 3, [Ir2(cp*)2(AVB)2BDP][2CF3SO3] 4, [Ru2(p-cymene)2(AVB)2BDPCC][2CF3SO3] 5 and [Ir2(cp*)2(AVB)2BDPCC][2CF3SO3] 6. The synthesized complexes are fully characterized using multiple analytical techniques, including elemental analysis, 1H NMR, 13C NMR, 19F NMR (NMR = Nuclear Magnetic Resonance), Infrared Radiation (IR), Electrospray Ionization-Mass Spectrometry (ESI-MS), Ultraviolet-visible (UV-Vis) and fluorescence spectroscopy. The structures of these complexes are further rationalized using density functional theory (DFT) calculations. The antiproliferative activity of the neutral and dinuclear cationic complexes is evaluated in vitro in different human cancer cell lines. These complexes are found to be active against different cancer cell lines with half maximal inhibitory concentration (IC50) values between 1 and 5 µM. Complexes 5 and 6 displayed the lowest IC50 values in all the cell lines studied. The activity of 5 and 6 is comparable to that of the well-known chemotherapy drug doxorubicin. Detailed biophysical studies indicate that complexes 5 and 6 exhibit very good Deoxyribonucleic acid (DNA) binding properties, causing the unwinding of the double helix, which is a probable reason for their high cytotoxicity.

Efficient Energy Transfer (EnT) in Pyrene- and Porphyrin-Based Mixed-Ligand Metal-Organic Frameworks.

Designing and synthesizing the ordered light-harvesting systems, possessing complementary absorption and energy-transfer process between the chromophores, are essential steps to accomplish successful mimicking of the natural photosynthetic systems. Metal-organic frameworks (MOFs) can be considered as an ideal system to achieve this due to their highly ordered structure, superior synthetic versatility, and tailorable functionality. Herein, we have synthesized the new light-harvesting mixed-ligand MOFs (MLMs, MLM-1-3) via solvothermal reactions between a Zr6 cluster and a mixture of appropriate ratio of 1,3,6,8-tetrakis(p-benzoic acid)pyrene and [5,10,15,20-tetrakis(4-carboxy-phenyl)porphyrinato]-Zn(II) ligands. The identical symmetry and connectivity of the two ligands of the MLMs was the key parameter of successful synthesis as a single MOF form, and the ample overlap between the emission spectrum of pyrene and the absorption spectrum of porphyrin provided the ideal platform to design an efficient-energy transfer (EnT) process within the MLMs. We obtained the nanoscale maps of the fluorescence intensities and lifetimes of microsize MLM grains for unambiguous visualization of EnT phenomena occurring between two ligands in MLMs. Moreover, due to complementary absorption and energy transfer between the two ligands in the MLMs, our MLMs performed as superior photoinduced singlet-oxygen generators, verifying the enhanced light-harvesting properties of the pyrene- and porphyrin-based MLMs.

Novel BODIPY-based Ru(II) and Ir(III) metalla-rectangles: cellular localization of compounds and their antiproliferative activities.

The first examples of Ru(ii) and Ir(iii) metalla-rectangles [1](4+)-[4](4+) containing a BODIPY-based linker are reported; some of these compounds exhibited highly selective anticancer activity and interact strongly with DNA as well as protein. The characteristic green fluorescence of a BODIPY ligand and associated aggregation-induced emission (AIE) permitted visualization of compounds inside the cells using confocal microscopy.