Injectable Adhesive Hydrogels for Soft tissue Reconstruction: A Materials Chemistry Perspective.

Injectable bioadhesives offer several advantages over conventional staples and sutures in surgery to seal and close incisions or wounds. Despite the growing research in recent years few injectable bioadhesives are available for clinical use. This review summarizes the key chemical features that enable the development and improvements in the use of polymeric injectable hydrogels as bioadhesives or sealants, their design requirements, the gelation mechanism, synthesis routes, and the role of adhesion mechanisms and strategies in different biomedical applications. It is envisaged that developing a deep understanding of the underlying materials chemistry principles will enable researchers to effectively translate bioadhesive technologies into clinically-relevant products.

Polymers and Composites Derived from Castor Oil as Sustainable Materials and Degradable Biomaterials: Current Status and Emerging Trends.

Recent years have seen rapid growth in utilizing vegetable oils to derive a wide variety of polymers to replace petroleum-based polymers for minimizing environmental impact. Nonedible castor oil (CO) can be extracted from castor plants that grow easily, even in an arid land. CO is a promising source for developing several polymers such as polyurethanes, polyesters, polyamides, and epoxy-polymers. Several synthesis routes have been developed, and distinct properties of polymers have been studied for industrial applications. Furthermore, fillers and fibers, including nanomaterials, have been incorporated in these polymers for enhancing their physical, thermal, and mechanical properties. This review highlights the development of CO-based polymers and their composites with attractive properties for industrial and biomedical applications. Recent advancements in CO-based polymers and their composites are presented along with a discussion on future opportunities for further developments in diverse applications.

In situ unsupervised learning using stochastic switching in magneto-electric magnetic tunnel junctions.

Spiking neural networks (SNNs) offer a bio-plausible and potentially power-efficient alternative to conventional deep learning. Although there has been progress towards implementing SNN functionalities in custom CMOS-based hardware using beyond Von Neumann architectures, the power-efficiency of the human brain has remained elusive. This has necessitated investigations of novel material systems which can efficiently mimic the functional units of SNNs, such as neurons and synapses. In this paper, we present a magnetoelectric-magnetic tunnel junction (ME-MTJ) device as a synapse. We arrange these synapses in a crossbar fashion and perform in situ unsupervised learning. We leverage the capacitive nature of write-ports in ME-MTJs, wherein by applying appropriately shaped voltage pulses across the write-port, the ME-MTJ can be switched in a probabilistic manner. We further exploit the sigmoidal switching characteristics of ME-MTJ to tune the synapses to follow the well-known spike timing-dependent plasticity (STDP) rule in a stochastic fashion. Finally, we use the stochastic STDP rule in ME-MTJ synapses to simulate a two-layered SNN to perform image classification tasks on a handwritten digit dataset. Thus, the capacitive write-port and the decoupled-nature of read-write path of ME-MTJs allow us to construct a transistor-less crossbar, suitable for energy-efficient implementation of in situ learning in SNNs. This article is part of the theme issue 'Harmonizing energy-autonomous computing and intelligence'.

Therapeutic Potential of Two Visible Light Responsive Luminescent photoCORMs: Enhanced Cellular Internalization Driven by Lipophilicity.

Herein we report the synthesis, characterization, and cellular internalization properties of two visible-light active luminescent Mn-based photoCORMs. The enhanced membrane permeability of the photoactive Mn carbonyl complex (photoCORM) derived from a designed lipophilic ligand namely, [Mn(CO)3(Imdansyl)(L1)](CF3SO3) (1) (where L1 = a diazabutadiene-based ligand containing two highly lipophilic adamantyl motifs, Imdansyl = dansylimidazole) promoted rapid internalization within human colorectal adenocarcinoma (HT-29) cells compared to [Mn(CO)3(Imdansyl)(L2)](CF3SO3) (2) (where L2 = a diazabutadiene ligand bearing two hydrophilic 1,3,5-triazaadamantyl group). Colocalization experiments using membrane stain indicate different extents of localization of the two CO complexes within the cellular matrix. Visible-light triggered CO release from the lipophilic photoCORM induced caspase-3/7 activation on HT-29 cells, which was detected using confocal microscopy. The rapid accumulation of the lipophilic photoCORM 1 in the cellular membrane resulted in more efficient CO-induced cell death compared to the hydrophilic analogue 2.

Nitrite Reduction by Trinuclear Copper Pyrazolate Complexes: An Example of a Catalytic, Synthetic Polynuclear NO Releasing System.

Two trinuclear CuII pyrazolato complexes with a Cu3(µ3-E)-core (E = O2- or OH-) and terminal nitrite ligands in two coordination modes were characterized crystallographically, spectroscopically, and electrochemically. One-electron oxidation of the µ3-O species produces a delocalized, mixed-valent, formally CuII2CuIII-nitrite, but no nitrate. In contrast, under reducing conditions-addition of PhSH as an electron and proton donor-both complexes mediate the reduction of nitrite, releasing NO.

Effect of bovine serum albumin on tartrate-modified manganese ferrite nano hollow spheres: spectroscopic and toxicity study.

The emerging category of magneto-fluorescent tartrate-modified MnFe2O4 nano hollow spheres (T-MnFe2O4 NHSs) can be considered as promising candidates for biomedical applications. The interaction of bovine serum albumin (BSA) with T-MnFe2O4 NHSs has been studied using several spectroscopic techniques, which suggest that the interaction occurs by an electrostatic mechanism. Furthermore, BSA enhances the charge transfer transition from the tartrate ligand to the metal ions along with the d-d transition of Fe3+ ions on NHSs surfaces at different pH. Very strong salt bridge formation occurs between the lysine of the BSA surface and the tartrate in basic medium (pH 10), followed by the acidic (pH 3) and neutral medium (pH 7), respectively. Systematic fluorescence microscopic analysis reveals that BSA significantly enhances the contrast of T-MnFe2O4 NHSs in UV and blue light excitation because of the extended charge transfer from BSA to T-MnFe2O4 NHSs. Our report demonstrates great potential in the field of nanotechnology and biomedical applications. In vitro toxicity analysis using RAW 264.7 celline and in vivo studies on Wister rats revealed that the T-MnFe2O4 NHSs are benign. Furthermore, T-MnFe2O4 NHSs also appear to be an antimicrobial agent. Therefore, T-MnFe2O4 NHSs can be explored for future therapeutic applications.

Spontaneous Resolution by Crystallization of an Octanuclear Iron(III) Complex Using Only Racemic Reagents.

The P and M enantiomers of the octanuclear [Fe8 (µ4 -O)4 (µ-4-Cl-pz)12 Cl4 ] complex, having T symmetry, were resolved by temporary substitution of chloride ligands by racemic 4-s Bu-phenolates and subsequent crystallization, where the (S)- and (R)-phenolates coordinate selectively to the M and P complexes, respectively. The complexes were characterized by circular dichroism analysis and X-ray structure determination. This work constitutes a rare example of enantiomeric recognition resulting in spontaneous resolution upon crystallization.

Incorporation of a Theranostic "Two-Tone" Luminescent Silver Complex into Biocompatible Agar Hydrogel Composite for the Eradication of ESKAPE Pathogens in a Skin and Soft Tissue Infection Model.

Microbial invasion and colonization of the skin and underlying soft tissues are among the most common types of infections, becoming increasingly prevalent in hospital settings. Systemic antibiotic chemotherapies are now extremely limited due to emergence of drug-resistant Gram-positive and multidrug-resistant Gram-negative bacterial strains. Topical administration of antimicrobials provides an effective route for the treatment of skin and soft tissue infections (SSTIs). Therefore, the development of new and effective materials for the delivery of these agents is of paramount importance. Silver is a broad-spectrum antibiotic used for the treatment and prevention of infections since ancient times. However, the high reactivity of silver cation (Ag+) makes its incorporation into delivery materials quite challenging. Herein we report a novel soft agar hydrogel composite for the delivery of Ag+ into infected wound sites. This material incorporates a Ag(I) complex [Ag2(DSX)2(NO3)2] (1; DSX = 5-(dimethylamino)- N, N-bis(pyridin-2-ylmethyl) naphthalene-1-sulfonamide) that exhibits a change in fluorescence upon Ag+ release and qualitatively indicates the end point of silver delivery. The antibacterial efficacy of the material was tested against several bacterial strains in an SSTI model. The complex 1-agar composite proved effective at eradicating the pathogens responsible for the majority of SSTIs. The theranostic (therapeutic/diagnostic) properties coupled with its stability, softness, ease of application, and removal make this material an attractive silver-delivery vehicle for the treatment and prevention of SSTIs.

A Luminescent Manganese PhotoCORM for CO Delivery to Cellular Targets under the Control of Visible Light.

A photoactive manganese carbonyl complex derived from dansylimidazole (Imdansyl), namely, [Mn(Imdansyl)(CO)3(phen)](CF3SO3) (1), has been synthesized and structurally characterized. This is the first luminescent manganese carbonyl-based photoCORM reported in the literature. This complex exhibits CO release under the exclusive control of low-power broadband visible light. The corresponding rhenium carbonyl complex, namely, [Re(Imdansyl)(CO)3(phen)](CF3SO3) (2), has also been reported, which is luminescent but sensitive only to UV-B (λ<315 nm) light. The entry of the manganese photoCORM into the human colorectal adenocarcinoma cells (HT-29) has been demonstrated with the aid of fluorescence microscopy. Irradiation of the photoCORM-loaded cancer cells to visible light leads to a dose-dependent apoptotic cell death.

Five- and Six-Coordinated Silver(I) Complexes Derived from 2,6-(Pyridyl)iminodiadamantanes: Sustained Release of Bioactive Silver toward Bacterial Eradication.

Silver(I) complexes of two designed tridentate ligands, namely, 2,6-(pyridyl)iminoditriazaadamantane (pydTAm) and 2,6-(pyridyl)iminodiadamantane (pydAm), have been synthesized and structurally characterized. [Ag(pydTAm)2](CF3SO3) (1), the hitherto unknown mer isomer of a silver(I) octahedral complex, crystallizes in a highly symmetric body-centered cubic I4̅3m space group. Quite in contrast, the AgI center in the analogous [Ag(pydAm)2](CF3SO3) (2) complex resides in a trigonal-bipyramidal geometry and crystallizes in a triclinic P1̅ space group with two crystallographically independent molecules in the asymmetric unit. Complex 1 exhibits exceptional solubility in aqueous media and leads to the efficient eradication of several bacterial strains upon sustained release of bioactive silver.

Synthesis, Structures, and CO Release Capacity of a Family of Water-Soluble PhotoCORMs: Assessment of the Biocompatibility and Their Phototoxicity toward Human Breast Cancer Cells.

Two manganese(I) carbonyl complexes derived from 2-(pyridyl)benzothiazole (pbt) and 1,10-phenanthroline (phen) release carbon monoxide (CO) under low-power broad-band visible-light illumination. CO photorelease from [Mn(CO)3(pbt)(PTA)]CF3SO3 (1, where PTA = 1,3,5-triaza-7-phosphaadamantane) is accompanied by an emergence of a strong fluorescence around 400 nm from almost nonfluorescent preirradiated 1. However, [Mn(CO)3(phen)(PTA)]CF3SO3 (2) showed no such phenomenon upon prolonged illumination under similar experimental conditions. The two analogous rhenium(I) complexes, namely, [Re(CO)3(pbt)(PTA)]CF3SO3 (3) and [Re(CO)3(phen)(PTA)]CF3SO3 (4), have also been synthesized and characterized to compare their photo properties with the manganese congeners. Complexes 3 and 4 exhibit moderate CO release upon irradiation with low-power UV light. All four complexes are highly soluble in anaerobic/aerobic aqueous media and are also considerably more stable when kept under dark conditions. The inherently luminescent rhenium complex 3 was utilized to demonstrate cellular internalization of these types of compounds by MDA-MB-231 (human breast cancer) cells, while the two biocompatible manganese(I) complexes (1 and 2) have been applied to assess the cell viability of these malignant cells upon CO delivery.

Luminescent Re(I) Carbonyl Complexes as Trackable PhotoCORMs for CO delivery to Cellular Targets.

A family of Re(I) carbonyl complexes of general formula [ReX(CO)3(phen)]0/1+ (where X = Cl-, CF3SO3-, MeCN, PPh3, and methylimidazole) derived from 1,10-phenanthroline (phen) exhibits variable emission characteristics depending on the presence of the sixth ancillary ligand/group (X). All complexes but with X = MeCN exhibit moderate CO release upon irradiation with low-power UV light and are indefinitely stable in anaerobic/aerobic environment in solution as well as in solid state when kept under dark condition. These CO donors liberate three, one, or no CO depending on the nature of sixth ligand upon illumination as studied with the aid of time-dependent IR spectroscopy. Results of excited-state density functional theory (DFT) and time-dependent DFT calculations provided insight into the origin of the emission characteristics of these complexes. The luminescent rheinum(I) photoCORMs uniformly displayed efficient cellular internalization by the human breast adenocarcinoma cells, MDA-MB-231, while the complex with PPh3 as ancillary ligand showed moderate nuclear localization in addition to the cytosolic distribution. These species hold significant promise as theranostic photoCORMs (photoinduced CO releasing molecules), where the entry of the pro-drug can be tracked within the cellular matrices.

A Redox-Induced Spin-State Cascade in a Mixed-Valent Fe3 (µ3 -O) Triangle.

One-electron reduction of a pyrazolate-bridged triangular Fe3 (µ3 -O) core induces a cascade wherein all three metal centers switch from high-spin Fe3+ to low-spin Fe2.66+ . This hypothesis is supported by spectroscopic data (1 H-NMR, UV-vis-NIR, infra-red, 57 Fe-Mössbauer, EPR), X-ray crystallographic characterization of the cluster in both oxidation states and also density functional theory. The reduction induces substantial contraction in all bond lengths around the metal centers, along with diagnostic shifts in the spectroscopic parameters. This is, to the best of our knowledge, the first example of a one-electron redox event causing concerted change in multiple iron centers.

A Theranostic Two-Tone Luminescent PhotoCORM Derived from Re(I) and (2-Pyridyl)-benzothiazole: Trackable CO Delivery to Malignant Cells.

A Re(I) carbonyl complex derived from 2-(2-pyridyl)-benzothiazole (pbt), [Re(H2O)(CO)3(pbt)](CF3SO3) (1), rapidly releases CO under low-power UV illumination. CO photorelease from 1 is accompanied by a change in luminescence from orange to deep blue. These two distinct luminescence signals have been successfully employed to track (a) the entry of the pro-drug 1 into cancer cells and (b) the end of the CO (drug) delivery step within the target.

Design strategies to improve the sensitivity of photoactive metal carbonyl complexes (photoCORMs) to visible light and their potential as CO-donors to biological targets.

The recent surprising discovery of the beneficial effects of carbon monoxide (CO) in mammalian physiology has drawn attention toward site-specific delivery of CO to biological targets. To avoid difficulties in handling of this noxious gas in hospital settings, researchers have focused their attention on metal carbonyl complexes as CO-releasing molecules (CORMs). Because further control of such CO delivery through light-triggering can be achieved with photoactive metal carbonyl complexes (photoCORMs), we and other groups have attempted to isolate such complexes in the past few years. Typical metal carbonyl complexes release CO when exposed to UV light, a fact that often deters their use in biological systems. From the very beginning, our effort therefore was directed toward identifying design principles that could lead to photoCORMs that release CO upon illumination with low-power (5-15 mW/cm(2)) visible and near-IR light. In our work, we have utilized Mn(I), Re(I), and Ru(II) centers (all d(6) ground state configuration) to ensure overall stability of the carbonyl complexes. We also hypothesized that transfer of electron density from the electron-rich metal centers to π* MOs of the ligand frame via strong metal-to-ligand charge transfer (MLCT) transitions in the visible/near-IR region would weaken metal-CO back-bonding and promote rapid CO photorelease. This expectation has been realized in a series of carbonyl complexes derived from a variety of designed ligands and smart choice of ligand/coligand combinations. Several principles have emerged from our systematic approach to the design of principal ligands and the choice of auxiliary ligands (in addition to the number of CO) in synthesizing these photoCORMs. In each case, density functional theory (DFT) and time-dependent DFT (TDDFT) study afforded insight into the dependence of the CO photorelease from a particular photoCORM on the wavelength of light. Results of these theoretical studies indicate that extended conjugation in the principal ligand frames as well as the nature of the donor groups lower the energy of the lowest unoccupied MOs (LUMOs) while auxiliary ligands like PPh3 and Br(-) modulate the energy of the occupied orbitals depending on their strong σ- or π-donating abilities. As a consequence, the ligand/coligand combination dictates the energy of the MLCT bands of the resulting carbonyl complexes. The rate of CO photorelease can be altered further by proper disposition of the coligands in the coordination sphere to initiate trans-effect or alter the extent of π back-bonding in the metal-CO bonds. Addition of more CO ligands blue shift the MLCT bands, while intersystem crossing impedes labilization of metal-CO bonds in several Re(I) and Ru(II) carbonyl complexes. We anticipate that our design principles will provide help in the future design of photoCORMs that could eventually find use in clinical studies.

Synthesis and assessment of CO-release capacity of manganese carbonyl complexes derived from rigid α-diimine ligands of varied complexity.

Four manganese carbonyl complexes of the type [MnBr(CO)3(NˆN)] (NˆN = α-diimine ligands) namely [MnBr(CO)3(bpy)] (1), [MnBr(CO)3(phen)] (2), [MnBr(CO)3(dafo)] (3) and [MnBr(CO)3(pyzphen)] (4) (where bpy = bipyridine, phen = 1,10-phenanthroline, dafo = 4,5-diazafluoren-9-one and pyzphen = pyrazino[2,3-f][1,10]-phenanthroline) have been synthesized and structurally characterized. These four complexes containing the fac-[Mn(CO)3] motif release CO upon illumination with low power visible and UV light. The CO release rates and the absorption maxima of the complexes are however very similar despite systematic increase in structural complexity in the rigid α-diimine ligand frames. This is quite in contrary to manganese carbonyl complexes derived from α-diimine ligands in which at least one of the imine functions is not part of the rigid ring systems. Results of this study will provide help in the future design of ligand frames suitable for the syntheses of photoCORMs to deliver CO to biological targets under the control of light.

Assessment of stress & related albuminuria in caregivers of severe mentally ill persons.

BACKGROUND & OBJECTIVES: The family caregivers of patients with chronic diseases are known to undergo psychiatric stress leading to oxidative damage to glomerular membrane of kidney resulting in proteinuria. This study was aimed to compare current anxiety, depression levels and urinary albumin:creatinine ratio between primary caregivers of chronic mental patients and matched controls, and also whether the urinary albumin : creatinine ratio is correlated with stress factors (state and trait anxiety level, depression and caregiver burden) amongst caregivers. METHODS: The present cross-sectional study included 131 subjects (93 primary caregivers of patients with major mental illness as cases and 38 normal controls). They completed the Burden Assessment Schedule of SCARF, State Trait Anxiety Inventory and Beck's Depression Inventory. A spot urine sample was tested for urinary albumin : creatinine ratio from all study subjects. RESULTS: Mean values of current State and Trait anxiety, depression, urinary albumin:creatinine ratio were significantly higher in caregivers than controls (P < 0.001). Urinary albumin : creatinine ratio was significantly correlated (P < 0.001) with State and Trait anxiety level, depression as well as caregiver burden. INTERPRETATION & CONCLUSIONS: The study demonstrated depression , anxiety and albuminuria amongst primary caregivers of patients with mental illness. Increase in the caregivers' burden, depression and anxiety resulted in an increase in the urinary albumin: creatinine ratio. This indicates that psychological stress is one of the determinants of albumin excretion rate in otherwise healthy subjects.

Assessment of insulin resistance and metabolic syndrome in drug naive patients of bipolar disorder.

The levels of fasting glucose, fasting insulin, insulin resistance (IR) and the prevalence of metabolic syndrome (MS) in a sample population of bipolar disorder (BPD) patients who were newly diagnosed and psychotropically naïve were assessed and compared with an age, sex and racially matched control population. 55 BPD-I patients (15-65 years) who were non-diabetic, nonpregnant, and drug naïve for a period of at least 6 months were included in the study. Diagnosis was made using the structured clinical interview for DSM-IV axis I disorders (SCID IV). IR was assessed using homeostasis model of insulin resistance (HOMA-IR); MS was defined according to National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III). Data were compared with 25 healthy controls. BPD patients had significantly higher mean levels of fasting plasma insulin (13.2 ± 9.2 vs. 4.68 ± 3.1 µIU/ml, p < 0.05), postprandial plasma insulin (27.2 ± 14.5 vs. 18.1 ± 9.3 µIU/ml, p < 0.05) and a higher value of HOMA-IR (3.16 ± 2.2 vs. 1.19 ± 0.8, p < 0.05) when compared to the controls. A significantly higher proportion of patients of BPD compared to controls were manifesting levels of fasting plasma glucose, serum triglyceride and blood pressure higher than the cut off while waist circumference and serum HDL cholesterol failed to show any significant difference in the proportion. There was a significantly higher proportion of prevalence of IR between BPD cases and controls (26/55 vs. 2/25, z value 9.97, p < 0.05) while there was no significant difference in proportion of prevalence of MS between these two groups. Within BPD patients, logistic regression analysis showed that age, sex or current mood status (depressed/manic) were not significantly predictive of presence or absence of MS or increased IR.

Goiter prevalence, urinary iodine, and salt iodization level in sub-Himalayan Darjeeling district of West Bengal, India.

National iodine deficiency disorders control program needs to be continuously monitored. Hence, a cross-sectional study was conducted during the period from April-May 2011 to assess the prevalence of goiter, status of urinary iodine excretion (UIE) level and to estimate iodine content of salts at the household level in Darjeeling district, West Bengal. Study subjects were 2400 school children, aged 8-10 years selected through "30 cluster" sampling methodology. Goiter was assessed by standard palpation technique, UIE was estimated by wet digestion method and salt samples were tested by spot iodine testing kit. Overall goiter prevalence rate was 8.7% (95% confidence intervals = 7.6-9.8) and goiter prevalence was significantly different with respect to gender. Median UIE level was 15.6 mcg/dL (normal range: 10-20 mcg/dL). About 92.6% of the salt samples tested had adequate iodine content of ≥15 ppm. Findings of the present study indicate that the district is in a transition phase from iodine-deficiency to iodine sufficiency.

Photoactivity of mono- and dicarbonyl complexes of ruthenium(II) bearing an N,N,S-donor ligand: role of ancillary ligands on the capacity of CO photorelease.

One monocarbonyl and one dicarbonyl complex of ruthenium(II), namely, [Ru(Cl)(CO)(qmtpm)(PPh3)]BF4 (2) and [Ru(Cl)(CO)2(qmtpm)]ClO4 (3), derived from the tridentate ligand 2-quinoline-N-(2'-methylthiophenyl)methyleneimine (qmtpm) have been synthesized and structurally characterized. The qmtpm ligand binds in a meridional fashion in these carbonyl complexes, and in 3, the two carbon monoxide (CO) ligands are cis to each other. Solutions of 2 in ethanol, chloroform, or acetonitrile rapidly release CO upon illumination with low-power (3-15 mW) light in the 300-450 nm range. Loss of CO from 2 brings about a dramatic color change from yellow to magenta because of the formation of [Ru(Cl)(MeCN)(qmtpm)(PPh3)]BF4 (4). In acetonitrile, photorelease of CO from 3 under 360 nm light occurs in two steps, and the violet photoproduct [Ru(Cl)(MeCN)2(qmtpm)](+) upon reaction with Ag(+) and PPh3 affords red [Ru(MeCN)2(qmtpm)(PPh3)](ClO4)2 (5). The structure of 5 has also been determined by X-ray crystallography. Reduced myoglobin assay confirms that 2 and 3 act as photoactive CO-releasing molecules (photoCORMs) that deliver 1 and 2 equiv of CO, respectively. The results of density functional theory (DFT) and time-dependent DFT studies confirm that electronic transitions from molecular orbitals with predominantly Ru-CO character to ligand-based π* orbitals facilitate CO release from these two photoCORMs. Complexes 2-5 have provided an additional opportunity to analyze the roles of the ancillary ligands, namely, PPh3, Cl(-), and MeCN, in shifting the positions of the metal-to-ligand charge-transfer bands and the associated sensitivity of the two photoCORMs to different wavelengths of light. Collectively, the results provide helpful hints toward the future design of photoCORMs that release CO upon exposure to visible light.