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Four mixed-ligand oxidovanadium(IV) complexes, [VIVO(L1-4)(phen)], 1-4, incorporating tridentate dibasic ONO donor hydrazone ligands (H2L1-4, general abbreviation H2L) derived from the condensation of 2-picolinyl hydrazide with 2-hydroxy acetophenone and its 5-substituted derivatives as primary ligands and 1,10-phenanthroline (phen) as auxiliary ligand have been synthesized in excellent yields. The complexes were characterized by elemental analyses, magnetic susceptibility measurements, and various spectral (e.g. IR, UV–Vis and EPR) studies. The molecular structure of one of the four complexes has been determined by single-crystal X-ray diffractometry. In 1, the hydrazone ligand is meridionally disposed of, coordinating through one enolic-O, one phenolic-O, and one imine-N. The other basal position is occupied by one pyridine-N of the phen moiety. The axial positions are occupied by one oxido-O atom and the other pyridine-N atom of the phen moiety. The complexes are paramagnetic with one unpaired electron (μeff ≈ 1.73 BM), suggesting no interaction with the neighboring molecules and are EPR active. The complexes display two d-d transitions, one near 725 and the other near 840 nm due to d xy → d xz , d yz and d xy → d x 2 − y 2 transitions, respectively. The other d-d transition associated with d xy → d z 2 transition was not observed as it falls in the UV region, which is masked by highly intense intra-ligand transitions. The complexes display one-electron oxidation peaks in the +0.75 to +0.89 V vs. Ag/AgCl region in the CH3CN solution that show a linear relationship with the Hammett parameter (σ) of the substituents in the aryloxy ring. [ABSTRACT FROM AUTHOR]

An imbalance in cysteine (Cys) levels in the cells and plasma has been identified as the risk indicator for various human diseases. The structural similarity of cysteine with its congener homocysteine and glutathione offers challenges in its measurement. Herein, we report a hydrogen‐bonded organic‐inorganic framework of Cu(II) (HOIF) for the selective detection of cysteine over other biothiols. The non‐fluorescent HOIF showed 12‐fold green emission in the presence of cysteine. The monomeric unit of HOIF is stabilized via intermolecular hydrogen bonds, resulting in a non‐porous network structure. Non‐interference from homocysteine, glutathione, and other competitive bio‐analytes revealed explicit affinity of HOIF for cysteine. Fluorimetric titration showed a wide working concentration window (650 nM–800 μM) for measuring cysteine in an aqueous medium. The mechanistic investigation involving HRMS, EPR, and UV‐vis spectroscopic studies revealed the decomplexation of HOIF with Cys, resulting in a fluorescence turn‐on response from the luminescent ligand. Validation using a commercial dye, "Cysteine Green", confirmed the prospect of HOIF for early diagnostic purposes. Utilizing the fluorescence turn‐on property of HOIF in the presence of cysteine, we measured cysteine quantitatively in the blood plasma samples. Bio‐imaging of endogenous cysteine in cancer cells indicated the ability of HOIF to monitor the intracellular cysteine. [ABSTRACT FROM AUTHOR]

High levels of unconjugated bilirubin (UB) in serum lead to asymptomatic and neonatal jaundice and brain dysfunctions. Herein, we have reported the detection of UB at as low as 1 μM in an aqueous alkaline medium using a Zn(II) complex. The specificity of the complex has been validated by the HPLC in the concentration window 6–90 μM, which is rare. The sensory response of the probe at physiological pH against nitro explosives developed it as an instant‐acting fluorosensor for picric acid (PA) and 2,4‐dinitrophenol (2,4‐DNP). Spectroscopic titration provided a binding constant of 4×105 M−1 with PA. The naked eye detection was found to be 15 μM. The solid‐state photoluminescent nature of the complex enabled it for PA sensing in the solid phase. Interestingly, the probe remained fluorescent in various volatile and non‐volatile organic solvents. As a result, it can also detect PA and 2,4‐DNP in a wide range of common organic media. NMR studies revealed the coordination of PA, 2,4‐DNP, and UB to the Zn(II) center of the probe, which is responsible for the observed quenching of the probe with the analytes. [ABSTRACT FROM AUTHOR]

Platelet activation and related cardiovascular complications are the hallmarks of type 2 diabetes (T2D). We investigated the mechanism of platelet activation in T2D using MS‐based identification of differentially expressed platelet proteins with a focus on glycosylated forms. Glycosylation is considered one of the common post‐translational modifications in T2D, and N/O‐linked glycosylation of glycoproteins (GPs)/integrins is known to play crucial roles in platelet activation. Our platelet proteome data revealed elevated levels of GPs GPIbα, GPIIbIIIa, GPIV (CD36), GPV and integrins in T2D patients. T2D platelets had elevated N‐linked glycosylation of CD36 at asparagine (Asn)408,417. Enrichment analysis revealed a close association of glycosylated CD36 with thrombospondin‐1, fibrinogen and SERPINA1 in T2D platelets. The glycosylation of CD36 has previously been reported to increase cellular uptake of long‐chain fatty acids. Our in silico molecular docking data also showed a favorable binding of cholesterol with glycosylated Asn417 CD36 compared to the non‐glycosylated form. We further investigated the CD36:LDL cholesterol axis in T2D. Elevated levels of oxidized‐low density lipoprotein (oxLDL) were found to cause significant platelet activation via CD36‐mediated stimulation of Lyn‐JNK signaling. Sulfo‐N‐succinimidyl oleate, an inhibitor of CD36, effectively inhibited oxLDL‐mediated platelet activation and adhesion in vitro. Our study suggests increased glycosylation of CD36 in T2D platelets as a potential route for oxLDL‐mediated platelet activation. The oxLDL:CD36 axis may thus be exploited as a prospective target to develop therapeutics against thrombosis in T2D. [ABSTRACT FROM AUTHOR]

The interplay between platelets and leukocytes contributes to the pathogenesis of inflammation, thrombosis, and cardiovascular diseases (CVDs) in type 2 diabetes (T2D). Our recent studies described alpha-ketoglutarate (αKG), a Krebs cycle intermediate metabolite as an inhibitor to platelets and leukocytes activation by suppressing phosphorylated-Akt (pAkt) through augmentation of prolyl hydroxylase-2 (PHD2). Dietary supplementation with a pharmacological concentration of αKG significantly inhibited lung inflammation in mice with either SARS-CoV-2 infection or exposed to hypoxia treatment. We therefore investigated if αKG supplementation could suppress hyperactivation of these blood cells and reduce thromboinflammatory complications in T2D. Our study describes that dietary supplementation with αKG (8 mg/100 g body wt. daily) for 7 days significantly reduced the activation of platelets and leukocytes (neutrophils and monocytes), and accumulation of IL1β, TNFα, and IL6 in peripheral blood of T2D mice. αKG also reduced the infiltration of platelets and leukocytes, and accumulation of inflammatory cytokines in lungs by suppressing pAkt and pP65 signaling. In a cross-sectional investigation, our study also described the elevated platelet–leukocyte aggregates and pro-inflammatory cytokines in circulation of T2D patients. T2D platelets and leukocytes showed an increased aggregation and thrombus formation in vitro. Interestingly, a pre-incubation of T2D blood samples with octyl αKG significantly suppressed the activation of these blood cells and ameliorated aggregate/thrombus formation in vitro. Thus, suggesting a potential therapeutic role of αKG against inflammation, thrombosis, and CVDs in T2D. Heightened inflammation and thrombosis exist in blood of T2D mice and patients. Lung inflammation is predominant in T2D mice. Dietary supplementation with a pharmacological concentration of α-ketoglutarate (αKG) significantly inhibited systemic and lung inflammation in T2D mice by downmodulating Akt and P65 activation in platelets and leukocytes, suggesting a therapeutic uses of this metabolite against thromboinflammation in diabetes. [ABSTRACT FROM AUTHOR]

Lab-on-a-paper-based devices are promising alternatives to the existing arduous techniques for point-of-need monitoring. The present work reports an instant and facile method to produce a microfluidic paper-based analytical device (μPAD). The fabricated μPAD has been used to detect hypochlorite (OCl−) by incorporating newly synthesized chromo-fluorogenic ratiometric probes 1 and 2 into the sample reception zone. The probes showed high selectivity and fast response (<10 s) toward OCl− with an excellent linear relationship in the concentration range of 0–100 μM. The concentration-dependent fluorometric change driven by the reaction of 1@μPAD with OCl− has been monitored using gel-doc imaging systems, which is unprecedented. Digitizing the intensity of the colour solution with different mathematical models of colour has developed a straightforward method for monitoring OCl− without any interference from its competitors. 1@μPAD can detect OCl− at ∼10 times lower than the WHO recommended limit. The detection limit of 1@μPAD via a digital camera-based fluorescence technique was found to be better over digital camera-based cuvette assays. Therefore, 1@μPAD has been successfully utilized to monitor OCl− in actual environmental water samples with portability, ease of use, and sensitivity. The analytical RSD was found to be ≤3% based on fluorimetric detection using 1@μPAD. The chemodosimetric reaction between OCl− and the probe was evidenced by UV-vis and fluorescence spectroscopy, 1H NMR, and ESI-MS. The rapid response time, biocompatibility, low cytotoxicity, 100% aqueous solubility, ratiometric feature, and exclusive OCl− selectivity over other competitive ROS/RNS successfully lead to the application of the probes for bioimaging of exogenous as well as endogenous OCl− in normal cells (HEK293) and cancerous cells (HeLa). [ABSTRACT FROM AUTHOR]

A five-coordinated {Mn(NO)}6 complex of Mn(II)–porphyrinate, [Mn(TMPP2−)(NO)], 1 {TMPPH2 = 5,10,15,20-tetrakis(4-methoxyphenyl)porphyrin}, upon reaction with two equivalents of superoxide (O2−) in THF at −40 °C results in the corresponding MnIII–OH complex [MnIII(TMPP2−)(OH)], 2, via the formation of a putative MnIII–peroxynitrite intermediate. Spectral studies and chemical analysis suggest that one equivalent of superoxide ion is consumed to oxidize the metal center of complex 1 leading to [MnIII(TMPP2−)(NO)]+, while the subsequent equivalent reacts with [MnIII(TMPP2−)(NO)]+ to form the corresponding peroxynitrite intermediate. UV-visible and X-band EPR spectroscopic studies suggest the involvement of a MnIV–oxo species in the reaction, which forms through the O–O bond cleavage of the peroxynitrite moiety with concomitant release of NO2. The formation of MnIII–peroxynitrite is further supported by the well-established phenol ring nitration experiment. The released NO2 has been trapped using TEMPO. It should be noted that in cases of MnII–porphyrin complexes, the reaction with superoxide generally proceeds through a SOD-like pathway where the first equivalent of superoxide ion oxidizes the MnII center and itself is reduced to peroxide (O22−), while the subsequent equivalent of superoxide reduces the MnIII center with the release of O2. In contrast, here the second equivalent of superoxide reacts with the MnIII–nitrosyl complex and follows a NOD-like pathway. [ABSTRACT FROM AUTHOR]

Fluorescence spectroscopic studies of a pair of new oxido‐vanadium(V) compounds with biological thiols, such as homocysteine (Hcy), cysteine (Cys), and glutathione (GSH), have been investigated in this article. Despite notable progress in vanadium‐thiol chemistry, no attention has been paid to exploring vanadium‐based optical probes to study their interaction with biothiols. For this purpose, two oxido‐vanadium(V) compounds, 1 and 2, have been prepared involving a tridentate ONO donor‐based luminescent coumarin‐derived ligand. Single crystal X‐ray diffraction analysis, NMR (1H, 13C, and 51V) spectroscopy, XPS, and DFT calculations have been used to establish their identities. The vanadium center in these compounds has a distorted octahedral environment. In compound 2, a methanol molecule is coordinated to the vanadium(V) center in the trans position of the terminal oxido moiety. The latter exerts a strong trans‐labilizing influence on the coordinating methanol. Both 1 and 2 are weakly fluorescent. Photophysical investigations of the vanadium complexes in aqueous media at physiological pH (7.4) in the presence of various biothiols and amino acids showed significant fluorescence enhancement (83‐fold) of the vanadium complexes, specifically with Hcy. The specific affinity of the complexes for Hcy remained unchanged even in the presence of other biothiols and amino acids. Kinetic investigation reveals pseudo‐first order behavior of the compound with Hcy. Mechanistic studies have manifested that Hcy‐induced reduction triggers the decomplexation of the vanadium compound, followed by hydrolysis and subsequent cyclization. Time‐correlated single photon counting suggested that the radiative rate constant (kr) of 1 and 2 in the presence of Hcy serves as the prime factor for the fluorescence enhancement of the medium. Compound 1 has been tested efficiently for Hcy measurement in blood plasma rendering it suitable for practical applications. [ABSTRACT FROM AUTHOR]