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Quercetin is one of the most bioactive and common dietary flavonoids, with a significant repertoire of biological and pharmacological properties. The biological activity of quercetin, however, is influenced by its limited solubility and bioavailability. Driven by the need to enhance quercetin bioavailability and bioactivity through metal ion complexation, synthetic efforts led to a unique ternary Ce(III)-quercetin-(1,10-phenanthroline) (1) compound. Physicochemical characterization (elemental analysis, FT-IR, Thermogravimetric analysis (TGA), UV-Visible, NMR, Electron Spray Ionization-Mass Spectrometry (ESI-MS), Fluorescence, X-rays) revealed its solid-state and solution properties, with significant information emanating from the coordination sphere composition of Ce(III). The experimental data justified further entry of 1 in biological studies involving toxicity, (Reactive Oxygen Species, ROS)-suppressing potential, cell metabolism inhibition in Saccharomyces cerevisiae (S. cerevisiae) cultures, and plasmid DNA degradation. DFT calculations revealed its electronic structure profile, with in silico studies showing binding to DNA, DNA gyrase, and glutathione S-transferase, thus providing useful complementary insight into the elucidation of the mechanism of action of 1 at the molecular level and interpretation of its bio-activity. The collective work projects the importance of physicochemically supported bio-activity profile of well-defined Ce(III)-flavonoid compounds, thereby justifying focused pursuit of new hybrid metal-organic materials, effectively enhancing the role of naturally-occurring flavonoids in physiology and disease.

Graphical abstract, Highlights • Development of a “real-life” exposure system to ambient PM1 and PM2.5 particles for Wistar rats. • Blood transcriptome analysis identified differentially expressed genes as candidate biomarkers in PM1 and PM2.5 groups. • Pathway analysis revealed differentially regulated gene expression in inflammation signaling. • Identification of candidate metals for possible correlation with the identified candidate genes leading to the development of AOPs., Exposure to particulate matter (PM) is one of the most important environmental issues in Europe with major health impact. Various sizes of PM are suspended in the atmosphere and contributes to ambient air pollution. The current study aimed to explore the differential gene expression in blood, and the effect on the respective biological signaling pathways in Wistar rats, after exposure to PM2.5 and PM1 ambient air particles for an eight-week period. A control group was included with animals breathing non-filtered atmospheric air. In parallel, filtered PM2.5 and PM1 was collected in separate samplers. The results after whole genome microarray analysis showed 23 differentially expressed genes (DEGs) between control and PM2.5 group. In addition, pairwise comparison between control and PM1 group displayed 5635 DEGs linked to 69 biological pathways involved in inflammatory response, cell cycle and carcinogenicity. The smaller the size of the inhaled particles, the more gene alterations are triggered compared to non-filtered air group. More specifically, in inflammation signaling procedures differentially regulated gene expression was shown for interleukin-4 (IL-4), IL-7, IL-1, IL-5, IL-9, IL-6 and IL-2. We have identified that RASGFR1, TRIM65, TRIM33, PLEKHB1, CAR4, S100A8, S100A9, ALPL, NP4 and the PROK2 genes are potential targets for the development of adverse outcome pathways (AOPs) due to “real-life” exposure of Wistar rats. Particle measurements during the exposure period showed elevated concentrations of Fe, Mn and Zn in both PM1 and PM2.5 filter fractions, and of Cu in PM2.5. In addition, water-soluble concentration of metals showed significant differences between PM1 and PM2.5 fractions for V, Zn, As, Pb and Mn. In summary, in this study specific gene biomarkers of exposure to ambient air have been identified and heavy metals that are possibly linked to their altered regulation have been found. The results of this research will pave the way for the development of novel AOPs concerning the health effects of the environmental pollution.

The importance of structural speciation in the control of chemical reactivity in Ni(II) binary-ternary systems, involving (O,O,N)-containing substrates (1,1’-iminodi-2-propanol), and aromatic chelators (2,2’-bipyridine, 1,10-phenanthroline), prompted the systematic synthesis of new crystalline materials characterized by elemental analysis, FT-IR, UV-Visible, Luminescence, TGA, magnetic susceptibility, and X-ray crystallography. The structures contain mononuclear octahedral assemblies, the lattice architecture of which exemplifies reaction conditions under which conformational variants and solvent-associated lattice-imposed complexes are assembled. Transformations between complex species denote their association with reactivity pathways, suggesting alternate synthetic methodologies for their isolation. Theoretical work (Hirshfeld, Electrostatic Potential, DFT) signifies the impact of crystal structure on energy profiles of the generated species. The arisen physicochemical profiles of all compounds portray a well-configured interwoven network of pathways, projecting strong connection between structural speciation and Ni(II) reactivity patterns in organic-solvent media. The collective results provide well-defined parameterized profiles, poised to influence the synthesis of new Ni(II)-iminodialcohol materials with specified structural-magneto-optical properties.

Novel antimicrobial compounds can be added to foods directly or incorporated into packaging materials in order to improve food safety and shelf life. One such potential antimicrobial compound is the bioinorganic complex Co(II)-citrate (NH4)4[Co(C6H5O7)2] (Co-cit). Its antimicrobial activity against Listeria monocytogenes, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa was investigated in solution, both alone and in combination with existing preservatives. The antimicrobial activity of poly(lactic acid) films (PLA) with incorporated Co-cit (23.3% w/w) against L. monocytogenes was determined using culture medium and model foods (slices of turkey ham and smoked salmon). In nutrient broth, without preservatives, all four bacteria were significantly (p < 0.05) inhibited by 0.5 mM Co-cit, and L. monocytogenes and P. aeruginosa were the most sensitive. The addition of preservatives to the broth increased the antimicrobial activity of Co-cit in many cases, but not in a way that was consistent between the different bacteria investigated and was likely due to additional physiological stress exerted on the cells rather than any effect on the activity of the Co-cit itself. PLA films with Co-cit were bacteriostatic against L. monocytogenes on artificial media and on foods. However, in the latter case, the PLA film itself was the main contributor to the inhibition. Composite PLA-(Co-cit) films exhibited antimicrobial activity against foodborne bacteria and have potential application as active packaging materials to enhance food safety.

Supplementary cementing materials (SCMs) and the challenges associated with admixture compatibility and durability performance are continuous challenges for the construction industry. Utilizing SCMs has apparent benefits in reducing the carbon footprint and improving the durability performance of concrete structures. This work investigates the performance of mortars composed of Portland limestone cement, calcium carbonate, butyl stearate, and oleic acid. The effort focuses on transport properties using electrical resistivity, chloride migration, porosity, and water permeability measurements. Then, various methods based on the last parameters are compared to assess the changes in the effective chloride diffusion coefficient and the intrinsic liquid water permeability. Measurements for drying shrinkage, thermal expansion, and compressive strength are conducted to verify durability and mechanical performance. The effect of the admixture addition on the service life of a structure fully submerged in marine exposure conditions is then evaluated using Fick’s second law of diffusion and the approach described by FIB model code 34. The results indicate that incorporating calcium carbonate, butyl stearate, and oleic acid in mortar mixtures provides enhanced durability compared to plain Portland limestone cement mortars.

A series of homologous Schiff bases N,N′-bis[(4-decyloxy-salicylideneamino)-n-propyl]-piperazine] (ZOPPH2), and N,N′-bis[(4-dodecyloxy-benzylideneamino)-n-propyl]-piperazine (DBPP)(1), based on 1,4-bis(3-amino-propyl)-piperazine (APPZ), were designed and synthesized, with APPZ serving as the piperazine core, bilaterally flanked by extended alkyl chain-containing antennae. Driven by the pursuit of metallomesogenic materials bearing liquid crystalline state properties, chemical reactivity toward divalent metals Co(II) and Cu(II), in alcoholic or tetrahydrofuran/dimethylsulfoxide media, led to compounds [{Co(ZOPP)}(ClO4)]2.(CH3OH).2(CH3)2SO(2) and [Cu(APPZ)Cl]Cl(3). All materials were characterized by elemental analysis, spectroscopic techniques (UV–Visible, FT-IR, NMR where appropriate), molar conductivity, and X-ray crystallography. Physicochemical characterization emphasizes the a) importance of N,O-containing Schiff anchors in metal ion binding, b) significance of the phenolic moiety, on the flanks of the Schiff ligands, in promoting either metal ion complexation or dissociation of the Schiff base at the azomethine moiety junction, thereby altering metal ion chemical reactivity, and c) observed oxidation of Co(II) to Co(III) upon mononuclear complex formation. Hybrid DFT calculations on DBPP and ZOPPH2 suggest increased reactivity of the Schiff CH N moiety, in the absence of the phenolic moiety, and concurrent metal ion presence, thereby lending credence to the notion of metal-assisted rupture of the specific bond in DBPP and the emergence of specific metal-ligand product(s). Collectively, the data denote the significance of structural features of piperazine-core Schiff antennae ligands in a) promoting chemical reactivity toward transition metals, b) defining metal-ligand complexation and lattice architecture, and c) parameterizing such chemical reactivity into synthetic advances toward new materials with well-defined solid-state architecture, lattice and physicochemical properties.

Cadmium is a metallotoxin, amply encountered in the environment and derived through physical and anthropogenic activities. Its entry in various organisms leads through water and the food chain to humans, thereby inducing a plethora of pathophysiologies. Delineation of the interactive role of cadmium with physiological and physiologically relevant substrates, requires well-defined forms of cadmium arising from such interactions along with the ensuing chemical reactivity amounting to toxic manifestations and health aberrations. To implement such efforts, low molecular mass substrate metal ion binders are needed, forming species with enhanced solubility and bioavailability. To that end, α-hydroxy isobutyric acid (HIBAH2) was used in pH-specific synthetic efforts involving bulky aromatic chelators 2,2′-bipyridine (2,2′-bipy) and 1,10-phenanthroline (phen), thus leading to new crystalline materials [Cd(C4H7O3)2]n(1), [Cd(C4H7O3)2(H2O)2](2), [{Cd2(C4H7O3)2(C10H8N2)2(H2O)2}(NO3)2]n·nH2O(3), and [{Cd2(C4H7O3)2(C12H8N2)2(H2O)2}(NO3)2]n·2nH2O(4), which were physicochemically characterized (elemental analysis, FT-IR, NMR, ESI-MS, and X-ray crystallography) in the solid state and solution. Their physicochemical characteristics led to their employment in tissue-specific biological toxicity studies in three different cell lines. Their toxicity profile (cell viability, morphology, chemotacticity) was correlated through genetic biomarkers to apoptotic-necrotic processes, thereby shedding light on cadmium cellular toxicity processes. Finally, the cytoprotective action of specific chelators was examined, lending credence to the notion that appropriately structured chelators and antioxidants may be used as effective deterrent to cadmium toxicity. Collectively, structure-specificity linked to tissue-specific toxicity profiling in well-defined binary-ternary Cd(II)-HIBAH2 systems exemplifies that metal ion's aberrant interactions in the cellular milieu, meriting further probing into the development of efficient chelators in cadmium detoxification.

The quest for effective treatments of oxidative stress has concentrated over the years on new nanomaterials with improved antioxidant and antiradical activity, thereby attracting broad research interest. In that regard, research efforts in our lab were launched to pursue such hybrid materials involving a) synthesis of silica gel matrices, b) evaluation of the suitability of atoxic matrices as potential carriers for the controlled release of V(IV)(VOSO4), V(V)(NaVO3) compounds and a newly synthesized heterometallic lithium-vanadium(IV,V) tetranuclear compound containing vanadium-bound hydroxycarboxylic 1,3-diamine-2-propanol-N,N,N′,N′-tetraacetic acid (DPOT), and c) investigation of structural and textural properties of silica nanoparticles (NPs) by different and complementary characterization techniques, inquiring into the nature of the encapsulated vanadium species and their interaction with the siloxane matrix, collectively targeting novel antioxidant and antiradical nanomaterials biotechnology. The physicochemical characterization of the vanadium-loaded SiO2 NPs led to the formulation of optimized material configuration linked to the delivery of the encapsulated antioxidant-antiradical load. Entrapment and drug release studies showed a) the competence of hybrid nanoparticles with respect to encapsulation efficiency of the vanadium compound (concentration dependence), b) congruence with the physicochemical features determined, and c) a well-defined release profile of NP load. Antioxidant properties and the free radical scavenging capacity of the new hybrid materials (containing VOSO4, NaVO3, and V-DPOT) were demonstrated through a) 2-diphenyl-1-picrylhydrazyl (DPPH) free radical, and b) intracellular-extracellular reactive oxygen species (ROS) assays, through UV–Visible spectroscopy techniques, collectively showing that the hybrid silica NPs (empty-loaded) could serve as an efficient platform for nanodrug formulations counteracting oxidative stress.

Vanadium has been known to exhibit numerous functions in biological systems, projecting exogenous activity linked to regulatory roles in cell metabolism and insulin mimesis. Poised to probe into the vanadium adipogenic potential, reflecting on efficient anti-diabetic drugs, research was launched in our labs to pursue the (a) synthesis of diversely structured Schiff base ligands, as vanadium chelating binders, containing a variably configured o-vanillin core with a specified common organic o-aminophenol tether, (b) synthesis of a family of well-defined soluble vanadium-Schiff base compounds, bearing the above mentioned Schiff ligands (and in one case 4,4′-bipyridine), (c) study of their toxicity profile and adipogenic activity in 3T3-L1 fibroblasts toward mature adipocytes, and (d) determination of molecular biological targets linked to the vanadium-induced cell differentiation process, thereby unravelling factors impacting signaling pathways influencing insulin mimesis. The results suggest that (a) all emerging vanadospecies contain V(V) mononuclear centers bound to Schiff bases (and 4,4′-bipyridine), (b) a well-defined (solid-state and solution) physicochemical profile of all species justifies their selection in biological studies, (c) the vanadium toxicity profile is strongly related to the form of V(V) (complexed forms, substrate-ligand nature), (d) there is a structure-specific behavior of vanadium influencing adipogenesis, and (e) molecular target loci are also influenced by vanadoforms in a structure-specific fashion, thereby collectively projecting an interwoven role of factors emanating from vanadium and impacting cell differentiation and insulin mimetic activity. The so far accrued knowledge constitutes the basis for further development of biomarker-driven structure-specific vanadodrugs, contributing through insulin biomimicry to therapeutic technologies in Diabetes mellitus.

Diabetes mellitus is a debilitating disease, plaguing a significant number of people around the globe. Attempts to develop new drugs on well-defined atoxic metalloforms, which are capable of influencing fundamental cellular processes overcoming insulin resistance, has triggered an upsurge in molecular research linked to zinc metallodrugs. To that end, meticulous efforts were launched toward the design and synthesis of materials with insulin mimetic potential. Henceforth, trigonelline and N-(2-hydroxyethyl)-iminodiacetic acid (HeidaH2) were selected as organic substrates seeking binding to zinc (Zn(II)), with new crystalline compounds characterized by elemental analysis, FT-IR, X-rays, thermogravimetry (TGA), luminescence, NMR, and ESI-MS spectrometry. Physicochemical characterization was followed by in vitro biochemical experiments, in which three out of the five zinc compounds emerged as atoxic, exhibiting bio-activity profiles reflecting enhanced adipogenic potential. Concurrently, well-defined qualitative–quantitative experiments provided links to genetic loci responsible for the observed effects, thereby unraveling their key involvement in signaling pathways in adipocyte tissue and insulin mimetic behavior. The collective results (a) signify the quintessential role of molecular studies in unearthing unknown facets of pathophysiological events in diabetes mellitus II, (b) reflect the close associations of properly configured molecular zincoforms to well-defined biological profiles, and (c) set the stage for further physicochemical-based development of efficient zinc antidiabetic metallodrugs.

The benefits of partial replacement of Portland cement by limestone are well established. This study investigates the impact of zinc and butyl stearates, as water-repellent additives, on the compressive strength, flexural strength, water penetration, absorption, chloride migration, density, drying shrinkage, and thermal expansion of Portland Limestone Cement mortars. The contents of stearates in this work are 1%, 2%, 3%, 4%, 5% by mass of binder content. Spectroscopic analyses using scanning electron microscopy and X-ray diffraction revealed discrete changes in the derived cement composite microstructure. The results of hardened mortar evaluation showed a negligible effect of zinc stearate on durability performance. In contrast to that, incorporation of butyl stearate in the mixtures enhanced resistivity to water permeability and chloride migration.

In this study, the exposome paradigm has been applied on a mother-child cohort adopting an optimised untargeted metabolomics approach for human urine followed by advanced bioinformatics analysis. Exposome-wide association algorithms were used to draw links between in utero co-exposure to metals and phthalates, metabolic pathways deregulation, and clinically observed phenotypes of neurodevelopmental disorders such as problems in linguistic, motor development and cognitive capacity. Children (n = 148) were tested at the first and second year of their life using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). Their mothers had been exposed to metals and phthalates during the pregnancy, according to human biomonitoring results from previously performed studies. Untargeted metabolomics analysis of biobanked urine samples from the mothers was performed using a combination of the high throughput analytical methods liquid chromatography-high resolution mass spectrometry (LC-HRMS) and nuclear magnetic resonance (NMR). Most perturbed metabolic pathways from co-exposure heavy metals and phthalates were pathways related to the tricarboxylic acid cycle (TCA cycle) and oxidative phosphorylation, indicating the possibility of disruption of mitochondrial respiration. Overproduction of reactive oxygen species (ROS); the presence of glutathione peroxidase 3 (GPx3) during pregnancy and presence of glutathione peroxidase 1 (GPx1) in the umbilical cord were linked to verbal development problems. Another finding of the study is that in real life, adverse outcomes occur as a combination of environmental and social factors, all of them acting synergistically towards the deployment of an observed phenotype. Finally, the two-steps association process (exposure to pathways and pathways to adverse outcomes) was able to (a) provide associations that are not evident by directly associating exposure to outcomes and (b) provides additional insides on the mechanisms of environmental disease.

Diabetes mellitus is a debilitating disease, plaguing a significant number of people around the globe. Attempts to develop new drugs on well‐defined atoxic metalloforms, which are capable of influencing fundamental cellular processes overcoming insulin resistance, has triggered an upsurge in molecular research linked to zinc metallodrugs. To that end, meticulous efforts were launched toward the design and synthesis of materials with insulin mimetic potential. Henceforth, trigonelline and N‐(2‐hydroxyethyl)‐iminodiacetic acid (HEIDAH2) were selected as organic substrates seeking binding to zinc (Zn(II)), with new crystalline compounds characterized by elemental analysis, FT‐IR, X‐rays, thermogravimetry (TGA), luminescence, NMR, and ESI‐MS spectrometry. Physicochemical characterization was followed by in vitro biochemical experiments, in which three out of the five zinc compounds emerged as atoxic, exhibiting bio‐activity profiles reflecting enhanced adipogenic potential. Concurrently, well‐defined qualitative–quantitative experiments provided links to genetic loci responsible for the observed effects, thereby unraveling their key involvement in signaling pathways in adipocyte tissue and insulin mimetic behavior. The collective results (a) signify the quintessential role of molecular studies in unearthing unknown facets of pathophysiological events in diabetes mellitus II, (b) reflect the close associations of properly configured molecular zincoforms to well‐defined biological profiles, and (c) set the stage for further physicochemical‐based development of efficient zinc antidiabetic metallodrugs. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

The plethora of flavonoid antioxidants in plant organisms, widespread in nature, and the appropriate metal ions known for their influence on biological processes constitute the crux of investigations toward the development of preventive metallodrugs and therapeutics in several human pathophysiologies. To that end, driven by the need to enhance the structural and (bio)chemical attributes of the flavonoid chrysin, as a metal ion complexation agent, thereby rendering it bioavailable toward oxidative stress, synthetic efforts in our lab targeted ternary Cr(III)-chrysin species in the presence of auxiliary aromatic N,N′-chelators. The crystalline metal-organic Cr(III)-chrysin-L (L = bipyridine (1) and phenanthroline (2)) compounds that arose were physicochemically characterized by elemental analysis, FT-IR, UV-Visible, ESI-MS, luminescence, and X-ray crystallography. The properties of these compounds in a solid state and in solution formulate a well-defined profile for the two species, thereby justifying their further use in biological experiments, intimately related to cellular processes on oxidative stress. Experiments in C2C12 myoblasts at the cellular level (a) focus on the antioxidant capacity of the Cr(III)-complexed flavonoids, emphasizing their distinct antiradical activity under oxidative stress conditions, and (b) exemplify the importance of structural speciation in Cr(III)-flavonoid interactions, thereby formulating correlations with the antioxidant activity of a bioavailable flavonoid toward cellular pathophysiologies, collectively supporting flavonoid introduction in new metallo-therapeutics.

emperature-sensitive crystalline phases, pertaining to discrete clusters of binary and ternary Co(II,III):iminodipropanol:(N,N'-aromatic binder) systems, were prepared. The rich structural speciation of such systems in alcoholic media and their unique structural, magnetic, and spectroscopic profiles have been demonstrated. The need to understand the chemical reactivity of such complex ternary Co(II)-(1,1'-iminodi-2-propanol) systems, in the presence of N,N'-aromatic chelators 2,2'-bipyridine and 1,10-phenanthroline and aromatic binder 4,4'-bipyridine in methanol, led to the synthetic development of well-defined hybrid metal-organic materials with discrete spectroscopic, structural, electrochemical, and magnetic properties. The surprisingly plethoric family of the prepared mononuclear-trinuclear-tetranuclear Co(II,III) clusters was characterized through elemental analysis, FT-IR, and X-ray crystallography. Enrichment of their physicochemical profile originated from electrochemical, optical (UV/Vis, luminescence), magnetic, and EPR studies, unequivocally supporting their structural formulation. Collectively, the experimentally and theoretically (Bond-Valence-Sum, Hirshfeld) perused structures project the influence of molecular stoichiometry and temperature on targeted synthetic efforts toward crystal engineering of discrete Co(II,III)-center assemblies, exemplifying structure-reactivity correlations and magneto-optical-structural attributes.

Metal-organic complexes bearing physiological substrates have been the target of several investigations, probing into the potential of well-defined atoxic metalloforms to influence fundamental cellular processes overcoming insulin resistance in Diabetes mellitus 2. Outstanding cases of such metals include zinc and vanadium, both being the target of intense synthetic and biological studies toward insulin mimesis. Owing to the close proximity in the periodic table, an early transition metal, titanium, emerges as another potential candidate of biologically relevant complexation, reflecting species capable of promoting insulin mimetic activity. Driven by the so far explored aqueous synthetic chemistry of Ti(IV)-hydroxycaboxylato systems, a well-defined Ti(IV)-citrate compound was synthesized under physiological conditions, isolated, and characterized, followed by its introduction in biological assays, targeting adipogenic events linked to glucose uptake and catabolism. The mononuclear Ti(IV)-citrate complex was introduced to 3T3-L1 cells, thereby probing into its biological activity (toxicity, morphology, migration, and adipogenic capacity). The results project an atoxic profile for the Ti(IV)-citrate species, thus justifying further incorporation in cellular differentiation processes, leading to mature adipocytes in a time- and concentration-dependent fashion. The experiments suggest that Ti(IV)-citrate is a competent agent promoting fibroblast differentiation, as evidenced by key adipogenic biomarkers, while concurrently exhibiting synergistic/enhancing action with insulin. The collective results show, for the first time, that an appropriately configured soluble-bioavailable complex Ti(IV) form exhibits a distinctly unique bioprofile, thereby lending credence to the notion that titanium metallopharmaceuticals hold merit as competent agents in adipogenesis and insulin mimesis in Diabetes mellitus.

Targeted tissue drug delivery is a challenge in contemporary nanotechnologically driven therapeutic approaches, with the interplay interactions between nanohost and encapsulated drug shaping the ultimate properties of transport, release and efficacy of the drug at its destination. Prompted by the need to pursue the synthesis of such hybrid systems, a family of modified magnetic core-shell mesoporous silica nano-formulations was synthesized with encapsulated quercetin, a natural flavonoid with proven bioactivity. The new nanocarriers were produced via the sol-gel process, using tetraethoxysilane as a precursor and bearing a magnetic core of surface-modified monodispersed magnetite colloidal superparamagnetic nanoparticles, subsequently surface-modified with polyethylene glycol 3000 (PEG3k). The arising nano-formulations were evaluated for their textural and structural properties, exhibiting enhanced solubility and stability in physiological media, as evidenced by the loading capacity, entrapment efficiency results and in vitro release studies of their load. Guided by the increased bioavailability of quercetin in its encapsulated form, further evaluation of the biological activity of the magnetic as well as non-magnetic core-shell nanoparticles, pertaining to their anti-amyloid and antioxidant potential, revealed interference with the aggregation of β-amyloid peptide (Aβ) in Alzheimer's disease, reduction of Aβ cellular toxicity and minimization of Aβ-induced Reactive Oxygen Species (ROS) generation. The data indicate that the biological properties of released quercetin are maintained in the presence of the host nanocarriers. Collectively, the findings suggest that the emerging hybrid nano-formulations can function as efficient nanocarriers of hydrophobic natural flavonoids in the development of multifunctional nanomaterials toward therapeutic applications.

In order to investigate the structure-specific bioactivity of Cd(II) in a cellular environment and delve into the associated biomolecular interactions, binary systems of that metal ion in the presence of the physiological naturally-occurring α-hydroxycarboxylic acid quinic acid were examined synthetically in a pH-specific mode. Two discrete polymeric compounds [Cd(C7H11O6)2]n·n/2H2O (1) and [Cd(C7H11O6)2]n·nH2O (2) were isolated and characterized through elemental analysis, FT-IR, NMR, TGA, and X-ray crystallography. Despite their discrete solid state metal-binding ligand coordination modes and lattice architecture, ESI-MS studies on 1 and 2 showed that both give rise to the same species upon dissolution in water. In vitro biological investigation of the toxicity profile of 2 in two cell lines, 3 T3-L1 and Saos-2, point out the influence of the coordination environment of Cd(II) on cell survival, migration and cellular morphology. The in vitro cytotoxic work showed a concentration- and tissue-specific pattern for the Cd-quinate system. Finally, the cytoprotective role of the chelator agent EDTA was investigated in these cell lines at various concentrations of 2, thereby providing insight into Cd(II) interactions with cellular targets compromising cellular integrity. The collective results, signify the a) importance of the aqueous chemistry of Cd(II) with biologically significant substrates, leading to discrete and isolable architectures reflecting binary Cd(II)-quinate composition, b) formulation of the cytotoxicity profile, based on well-defined Cd(II) species, and c) selection and use of appropriately configured organic chelators into future research linked to the development of preventive and/or therapeutic approaches pertaining to Cd(II) (de)toxification processes.

Diabetes mellitus comprises a group of metabolic abnormalities due to insulin deficiency and/or resistance. Obesity contributes to diabetes, with a strong causal relationship existing between diabetes and insulin resistance, especially in patients with Diabetes mellitus II. Adipocytes emerge as key constituents of adipose tissue physiology. In their pre-mature form to mature state transformation, adipocytes fully exemplify one of the key adipogenic actions of insulin. Poised to a) gain insight into adipogenesis leading to antidiabetic factors, and b) investigate adipogenesis through careful examination of insulin contributions to interwoven mechanistic pathways, a systematic comparative study was launched involving well-defined metal-citrates (zinc and vanadium), the chemical reactivity of which was in line with their chemistry under physiological conditions. Selection of the specific compounds was based on their common aqueous coordination chemistry involving the physiological chelator citric acid. Cellular maturation of pre-adipocytes to their mature form was pursued in the presence-absence of insulin and employment of closely linked genetic targets, key to adipocyte maturation (Peroxisome proliferator-activated receptor gamma (PPAR-γ), Glucose transporter 1,3,4 (GLUT 1,3,4), Adiponectin (ADIPOQ), Glucokinase (GCK), and Insulin receptor (INS-R)). The results show a) distinct adipogenic biological profiles for the metalloforms involved in a dose-, time- and nature-dependent manner, and b) metal ion-specific adipogenic response-signals at the same or higher level than insulin toward all selected targets. Collectively, the foundations have been established for future exploitation of the distinct metal-specific adipogenic factors contributing to the functional maturation of adipose tissue and their use toward hyperglycemic control in Diabetes mellitus.

With superparamagnetic iron oxide nanoparticles (SPIONs) increasingly attracting interest in life sciences, especially in applications such as cancer or Alzheimer's disease, the need for in vitro and in vivo investigation of their behavior, when taken up by structures of the immune system, becomes imperative. In this letter, thioflavin-T tagged core-shell SPIONs bound to amyloid beta 1–42 (A β 1-42) were imbued into macrophages in order to fully understand the effect of phagocytosis on functionalized T-SPIONs and cellular structures. Results after 24 h of exposure in macrophage cultures at various concentrations of T-SPIONs (both free and bound) indicate that the material is successfully phagocytosed, with an uptake above 60%, and cannot be considered cytotoxic, as proven by both tetrazole MTT colorimetric assays and trypan blue measurements. Concurrently, it does not affect the prooxidant–antioxidant balance in the cell culture. Taking into consideration that Α β 1-42 dissolves during phagocytosis, whereas the magnetic and fluorescent character of the silica-coated nanoparticles is maintained after a second phagocytosis cycle, a reuse process of T-SPIONs seems feasible, presenting multiple advantages.

Among transition and non-transition metals, thallium is a unique case of an element which, despite its known toxicity, provides interesting challenges through its biology and chemistry linked to diagnosis of human pathophysiologies. Poised to investigate in-depth the structural and electronic aspects of thallium involvement in physiological processes, the synthetic exploration of aqueous binary systems of Tl(I) with physiological binders from the family of hydroxycarboxylic acids (glycolic, lactic, mandelic and citric acid) was pursued in a pH-specific fashion. The isolated crystalline coordination polymers, emerging from that effort, were physicochemically characterized through elemental analysis, FT-IR, ESI-MS, 1H-/13C-NMR, and X-ray crystallography. The coordination environment of thallium in each molecular Tl(I) assembly, along with lattice dimensionality (2D 3D), reflects the contributions of the ligands, collectively exemplifying interactions probed into though BVS and Hirshfeld surface analysis. The results portray a well-defined solid-state and solution profile for all species investigated, thereby providing the basis for their subsequent selection into in vitro biological studies involving the (patho)physiological cell lines 3T3-L1, Saos-2, C2C12, and MCF-7. Biotoxicity profiles, encompassing cell viability, morphology, and cell growth support clearly a concentration-, time-, and cell tissue-specific behavior for the chosen Tl(I) compounds in a structure-specific fashion. Collectively, the chemical experimental data support the biological results in formulating a structure-specific behavior for Tl(I)-hydroxycarboxylato species with respect to biotoxicity mechanisms in a (patho)physiological environment. The accrued knowledge stands as the foreground for further investigation into the relevant biological chemistry of Tl(I) and molecular technologies targeting its sequestration and removal from cellular media.

The advent of biodegradable nanomaterials with enhanced antibacterial activity stands as a challenge to the global research community. In an attempt to pursue the development of novel antibacterial medicinal nanotechnology, we herein a) synthesized ionic-gelated chitosan nanoparticles, b) compared and evaluated the antibacterial activity of essential oils extracted from nine different herbs (Greek origin) and their combinations with a well-defined antibacterial Zn(II)-Schiff base compound, and c) encapsulated the most effective hybrid combination of Zn(II)-essential oils inside the chitosan matrix, thereby targeting well-formulated nanoparticles of distinct biological impact. The empty and loaded chitosan nanoparticles were physicochemically characterized by FT-IR, Thermogravimetric Analysis (TGA), Scanning Electron Microscopy (SEM), with the entrapment and drug release studies being conducted through UV-Visible and atomic absorption techniques. The antimicrobial properties of the novel hybrid materials were demonstrated against Gram positive (S. aureus, B. subtilis, and B. cereus) and Gram negative (E. coli and X. campestris) bacteria using modified agar diffusion methods. The collective physicochemical profile of the hybrid Zn(II)-essential oil cocktails, formulated so as to achieve optimal activity when loaded to chitosan nanoparticles, signifies the importance of design in the development of efficient nanomedicinal pharmaceuticals a) based on both natural products and biogenic metal ionic cofactors, and b) targeting bacterial infections and drug resistance.

Formation and accumulation of extracellular amyloid-beta ( $\text{A}\beta )$ peptide aggregates in the brain are associated with Alzheimer’s disease, a widespread age-related form of dementia, for which there is no effective treatment at present. It is essential to discover ways of visualizing and monitoring the progress of aggregation toward amyloidic plaques while at the same time therapeutic methods inhibiting the aggregation can be explored. Iron oxide nanoparticles Fe3O4 with size ~10 nm have been coated with silica SiO2 and Thioflavin-T (ThT), a non-toxic fluorescent dye binding to the amyloid- $\beta $ structures with a possible effect on fibril formation, and then added to $\text{A}\beta _{\mathrm {1-42}}$ phosphate-buffered saline solution, incubated for 30 min and extracted by magnetic separation. The magnetic ThT silica-coated nanoparticles with size ~20 nm have been characterized structurally and magnetically by powder X-ray powder diffraction, Fourier transform infrared spectroscopy, transmission electron microscopy, and vibrating sample magnetometer. Their affinity to $\text{A}\beta _{\mathrm {1-42}}$ peptide, examined by fluorescence microscopy and protein concentration measurements using the BCA Protein Assay Kit has been verified. Successful binding of magnetic silica nanoparticles, doped with ThT, to $\text{A}\beta _{\mathrm {1-42}}$ peptide provides a nanocarrier potentially exemplifying multiple functions, such as magnetic imaging, magnetic handling, drug delivery, fluorescence imaging, $\text{A}\beta $ binding, and $\text{A}\beta $ aggregation inhibition.

Utilizing bacteria in communications has emerged as a promising solution to delineating peculiarities at the nanoscale level. Usually, bacteria are used as carriers of molecules, which are exchanged in order to dissipate information. This work proposes a system, whereby bacterial concentration is used to transfer information. Chemotaxis plays a central role in the scheme. The investigation targets the examination and comparison of two different methodologies, where either the server uses chemorepellent or the clients use chemoattractant substances to bring about the chemotaxis effect. Performance of the proposed topologies was investigated through simulation. In the simulated experiments performed, random messages were encoded in the bacterial concentration using a simple on–off keying modulation, which then the receivers decode to recover the initial message. The experiments demonstrate the differences between the two strategies under various topologies, show the superior performance achieved in the case of chemoattractant clients, and highlight the influence of the parameters of distance, number of sensors and number of bacteria per pulse on the received signal amplitude and achievable bit error rate.

As advances in nanotechnology continue their ascending course, new areas of application for nanoscale communication open up, involving biological systems. Such systems have peculiarities that must be taken into consideration, when trying to study new communication paradigms based on micro-biological communication systems. In this paper, an innovative mathematical model is employed, in an effort to study message dissemination through bacterial communication in the form of delivery of information within a simple, biologically inspired, communication system consisting of bacteria, yet representative of the characteristics of biological nanocommunication environments. Stimulus spreading is being investigated within the realm of message dissemination in electromagnetic networks, for single and multiple infection sources using macro scale simulation techniques, with the help of a simulation tool, which was developed based on a commercial simulation suite. The observed results indicate that the mathematical model predictions are in strong agreement with the simulations described by Fick’s laws of diffusion and well-approximated through the Fisher–Kolmogorov–Petrovsky–Piscunov (FKPP) equation, enabling use of conventional simulation systems for fast biological nanosystem property investigation.

Due to its physical and chemical properties, bismuth (Bi(III)) is widely used in the treatment of several gastrointestinal and skin diseases, and infections caused by bacteria. Herein, its known antimicrobial potential was taken into consideration in the synthesis of two new hybrid ternary materials of Bi(III) with the physiological α-hydroxycarboxylic glycolic acid and 1,10-phenanthroline (phen), [Bi2(C2H2O3)2(C2H3O3)(NO3)]n. nH2O (1) and [Bi(C12H8N2)(NO3)4](C10H8N4) (2), aiming at improving its antibacterial properties. Their physicochemical characterization was carried out through elemental analysis, FT-IR, atomic absorption spectroscopy, single crystal X-ray diffraction, thermogravimetric analysis (TGA), photoluminescence, and 13C MAS-NMR techniques. The antimicrobial activity of the title complexes was directly linked to Bi(III) coordination environment and the incipient aqueous chemistry. For their antibacterial assessment, minimum inhibitory concentration (MIC), zone of inhibition (ZOI), and bacteriostatic-bacteriocidal activity were determined in various Gram positive (Staphylococcus aureus, Bacillus subtilis and Bacillus cereus) and Gram negative (Escherichia coli and Xanthomonas campestris) bacterial cultures, in reference to a positive control (ampicillin), encompassing further comparisons with literature data. The findings reveal that the new hybrid bismuth materials have significant antimicrobial effects against the employed bacteria. Specifically, 2 exhibits better antimicrobial properties than free Bi(NO3)3 and phen. On the other hand, 1 is bacteriostatic toward four microorganisms except X. campestris, with 2 being bacteriocidal toward four microorganisms except B. cereus. Collectively, the new hybrid, well-defined, and two of the rarely crystallographically characterized Bi(III) materials a) exhibit properties reflecting their physicochemical nature and reactivity, and b) are expected to contribute to the development of efficient metallodrugs against drug-resistant bacterial infections.

The pursuit of metal–organic materials involving In(III) with specified architecture and properties stands as a challenge in contemporary chemistry of hybrid inorganic–organic materials. Efforts in that direction have focused on the pH-specific synthesis of new compounds bearing a distinct family of organic ligands, i.e. α-hydroxycarboxylic citric, malic and lactic acid. The emerging new binary materials [In7(C6H4O7)8(H2O)]·(CH6N3)11·5H2O (1), [In(C4H4O5)2]n·nNH4·2nH2O (2) and [In(C3H5O3)2(C3H5.5O3)2] (3) reveal unique structural characteristics influencing lattice and spectroscopic properties. The physicochemical investigation of 1–3 (elemental analysis, FT-IR, NMR, X-ray crystallography, TGA) unravels variable nuclearity species of discrete and polymeric nature, essentially reflecting on the form of In(III) inorganic synthon and organic acid chelator properties interacting into various modes under pH-specific conditions. Mononuclear as well as polymeric composition, variable coordination number and ligand deprotonation state in the In(III) coordination sphere earmark the impact of the (a) coordination attributes of organic acids chelating In(III), with malic acid ostensibly possessing minimal requirements, beyond which multinuclear assemblies arise, and (b) use of appropriate inorganic/organic base to provide stability in the arisen lattice in the solid state. The architectural arrangement of the molecular assemblies in 1–3 project the importance of hydrogen-bonding interactions, which provide access to 2D lattices on the assembled metal–organic In(III) units through intervening water or counter ions. Collectively, the synthetic endeavor at the structural speciation level in binary aqueous In(III)-hydroxycarboxylic acid systems reveals a wealth of information, supporting key correlations on physicochemical profiling to be used further in the design and synthesis of new binary-ternary In(III) metal–organic materials in advanced applications.

The remarkable advances in biotechnology and health sciences have led to a significant production of data, such as high throughput genetic data and clinical information, generated from large Electronic Health Records (EHRs). To this end, application of machine learning and data mining methods in biosciences is presently, more than ever before, vital and indispensable in efforts to transform intelligently all available information into valuable knowledge. Diabetes mellitus (DM) is defined as a group of metabolic disorders exerting significant pressure on human health worldwide. Extensive research in all aspects of diabetes (diagnosis, etiopathophysiology, therapy, etc.) has led to the generation of huge amounts of data. The aim of the present study is to conduct a systematic review of the applications of machine learning, data mining techniques and tools in the field of diabetes research with respect to a) Prediction and Diagnosis, b) Diabetic Complications, c) Genetic Background and Environment, and e) Health Care and Management with the first category appearing to be the most popular. A wide range of machine learning algorithms were employed. In general, 85% of those used were characterized by supervised learning approaches and 15% by unsupervised ones, and more specifically, association rules. Support vector machines (SVM) arise as the most successful and widely used algorithm. Concerning the type of data, clinical datasets were mainly used. The title applications in the selected articles project the usefulness of extracting valuable knowledge leading to new hypotheses targeting deeper understanding and further investigation in DM. Keywords: Machine learning, Data mining, Diabetes mellitus, Diabetic complications, Disease prediction models, Biomarker(s) identification

In this work novel magnetic cationic liposomal nanoformulations were synthesized for the encapsulation of a crystallographically defined ternary V(IV)-curcumin-bipyridine (VCur) complex with proven bioactivity, as potential anticancer agents. The liposomal vesicles were produced via the thin film hydration method employing N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium (DOTAP) and egg phosphatidylcholine lipids and were magnetized through the addition of citric acid surface-modified monodispersed magnetite colloidal magnetic nanoparticles. The obtained nanoformulations were evaluated for their structural and textural properties and shown to have exceptional stability and enhanced solubility in physiological media, demonstrated by the entrapment efficiency and loading capacity results and the in vitro release studies of their cargo. Furthermore, the generated liposomal formulations preserved the superparamagnetic behavior of the employed magnetic core maintaining the physicochemical and morphological requirements for targeted drug delivery applications. The novel nanomaterials were further biologically evaluated for their DNA interaction potential and were found to act as intercalators. The findings suggest that the positively charged magnetic liposomal nanoformulations can generate increased concentration of their cargo at the DNA site, offering a further dimension in the importance of cationic liposomes as nanocarriers of hydrophobic anticancer metal ion complexes for the development of new multifunctional pharmaceutical nanomaterials with enhanced bioavailability and targeted antitumor activity.

Driven by the need to generate hybrid In(III)-(O,N) luminescent materials containing appropriately configured organic ligands, binary-ternary In(III) metal-organic systems involving the multidentate organic ligand DPOT, ethylenediamine (en) and phenanthroline (phen) were investigated under pH-specific conditions. The arisen materials [In2(C11H13N2O9)2](CH6N3)4·7H2O(1), [In3(C11H13N2O9)2(C2H8N2)2](C2H9N2)·4H2O(2), [In2(C11H13N2O9)2](CH6N3)6(Cl)2·6H2O(3), and [In2(C11H13N2O9)(C12H8N2)2(Cl)(H2O)]·7.5H2O(4) were characterized by analytical, spectroscopic (FT-IR, 13C-MAS NMR, luminescence) techniques, TGA and X-ray crystallography. The binary materials 1 and 3 exhibit dinuclear alkoxido-bridged In2O2 cores, with the fully-deprotonated organic ligand spanning both centers. Introduction of bidentate ethylenediamine leads to ternary trinuclear species 2, whereas phen introduction in 4 leads to a dinuclear asymmetric assembly, incorporating a chloride ion and a water molecule. Chemical transformations among 1–4 provide mechanistic insight into the nature of chelators, dictating nuclearity, coordination, composition and lattice-specific luminescence. The collective physicochemical properties in 1–4 present well-defined 1D-3D structural architecture-dimensionality and spectroscopic property correlations, pointing out criteria based on which synthon design, custom architecture and photoactivity are interwoven into the future development of In(III)-containing metal-organic hybrid materials.

Insulin resistance is identified through numerous pathophysiological conditions, such as Diabetes mellitus II, obesity, hypertension and other metabolic syndromes. Enhancement of insulin action and\or its complete replacement by insulin-enhancing or insulin-mimetic agents seems to improve treatment of metabolic diseases. Over the last decades, intensive research has targeted the investigation of such agents, with chromium emerging as an important inorganic cofactor involved in the requisite metabolic chemistry. Chromium in its trivalent state has been shown to play a central role in carbohydrate metabolism by enhancing insulin signaling, action, and thus the sensitivity of insulin-sensitive tissues. A very likely link between diabetes and obesity is the adipose tissue, which stores energy in the form of triglycerides and releases free fatty acids. To date, there is paucity of information on the exact mechanism of the chromium effect concerning insulin-activated molecular paths, such as adipogenesis. The aim of the present study is to delve into such an effect by employing a well-defined form of chromium (Cr(III)-citrate) on the a) survival of pre- and mature adipocytes (3T3-L1), b) endogenous cell motility, and c) insulin-enhancing adipogenic capacity. The emerging results suggest that Cr(III)-citrate a) is (a)toxic in a concentration- and time-dependent manner, b) has no influence on cell motility, c) can induce 3T3-L1 pre-adipocyte differentiation into mature adipocytes through elevation of tissue specific biomarker levels (PPAR-γ, GLUT 4 and GCK), and d) exemplifies structurally-based metal-induced adipogenesis as a key process contributing to the development of future antidiabetic metallodrugs.

Environmental metallotoxins (Cd, Hg, Pb, As, Cr) influence profusely human health. Consequently, clear research directives are required to probe the complexity of risk and disease associations with exposure to metallotoxins. Systems biology approaches targeting the exposome provide efficient routes to organ-tissue profiling, while concurrently distinguishing physiology from deviating potential disease states. Sample processing and biophysical-biochemical methods in concert with metallotoxin speciation describe hybrid molecular interactions with extra/intracellular targets, establishing networks on normal physiology-aberrant functions at the cellular, tissue-organ and whole organism levels. Omics technologies, combined with bioinformatics, delineate emerging interactions, generating profiles, genotypic-phenotypic relationships, and biomarkers key to elucidating adverse outcomes on health. Collectively, the emerging exposome description provides tools expediting physiology-disease assessment and validation, further supporting preventive diagnostic-prognostic and potentially therapeutic technologies.

Epithelial to mesenchymal transition (EMT) plays a key role in tumor progression and metastasis as a crucial event for cancer cells to trigger the metastatic niche. Transforming growth factor-β (TGF-β) has been shown to play an important role as an EMT inducer in various stages of carcinogenesis. Previous reports had shown that antitumor vanadium inhibits the metastatic potential of tumor cells by reducing MMP-2 expression and inducing ROS-dependent apoptosis. However, the role of vanadium in (TGF-β)-induced EMT remains unclear. In the present study, we report for the first time on the inhibitory effects of vanadium on (TGF-β)-mediated EMT followed by down-regulation of ex vivo cancer stem cell markers. The results demonstrate blockage of (TGF-β)-mediated EMT by vanadium and reduction in the mitochondrial potential of tumor cells linked to EMT and cancer metabolism. Furthermore, combination of vanadium and carboplatin (a) resulted in synergistic antitumor activity in ex vivo cell cultures, and (b) prompted G0/G1 cell cycle arrest and sensitization of tumor cells to carboplatin-induced apoptosis. Overall, the findings highlight the multifaceted antitumor action of vanadium and its synergistic antitumor efficacy with current chemotherapy drugs, knowledge that could be valuable for targeting cancer cell metabolism and cancer stem cell-mediated metastasis in aggressive chemoresistant tumors.

The interaction of human serum albumin (HSA) with amphiphilic block copolymer Pluronic F127 has been investigated by several physical methods. Interest in studying this system stems from a broad range of bioactivities involving both macromolecules. Serum albumins constitute a significant class of proteins in the circulatory system, acting as carriers for a wide spectrum of compounds or assemblies. Pluronic block copolymers have revealed their capacity to ferry a variety of biologically active compounds. Circular dichroism, rheological measurements, and differential scanning microcalorimetry (μDSC) were employed to get insight into the interaction betweeen the two macromolecules. The results reveal that Pluronic F127 induces conformational changes to albumin if it is organized in a micellar form, while albumin influences the self-assembly of Pluronic F127 into micelles or gels. F127 micelles, however, induce smaller conformational changes compared to ionic surfactants. The μDSC thermograms obtained for HSA and/or F127 show that HSA shifts the critical micellar temperature (cmt) to lower values, while concurrently the HSA denaturation behavior is influenced by F127, depending on its concentration. Rheological measurements on solutions of F127 17% have shown that a sol-to-gel transition occurs at higher temperatures in the presence of HSA and the resulting gel is weaker. The global profile on HSA/F127 systems was complemented by local information provided by EPR measurements. A series of X-band EPR experiments was performed with spin probes 4-(N,N'-dimethyl-N-hexadecyl)ammonium-2,2',6,6'-tetramethylpiperidine-1-oxyl iodide (CAT16) and 5-doxyl stearic acid (5-DSA). These spin probes bind to albumin sites and are sensitive to phase transformations in Pluronic block copolymer solutions. For a given F127 concentration, the spin probe binds only to HSA below cmt and migrates to the F127 micelles above cmt. The collective data suggest soft interactions between the macromolecules, with the emerging results projecting potential applications linked to reaching optimal conditions for certain drug formulations.

Efforts to comprehend the structural–spectrochemical correlations of crystalline metal–organic framework materials of Pb(II) with (a)cyclic and aromatic chelators linked to photoluminescent applications led to the hydrothermal pH-specific synthesis of crystalline materials [Pb{H2BTC}(phen)(H2O)]n·2nH2O(1), [Pb2{CBTC}]n(2), [Pb4(phen)8{CBTC}2(H2O)4]3·70.3H2O(3), and [Pb{HCTA}(H2O)2]n·nH2O(4). X-ray studies showed that 1–4 exhibit unique architectures linked to 2D–3D coordination polymers formulated by Z-type units composed of Pb2O2 cores, unusually high number of lattice–water molecules, and π–π and H-bond interactions. The contribution of the nature–structure properties of the aliphatic-(a)cyclic organic (poly)carboxylic/aromatic chelators-ligands to binary-ternary Pb(II) reactivity weaves into the assembly of supramolecular networks, thereby providing clear structural–spectroscopic inter-relationships exemplifying the observed photoluminescent activity in a distinct MOF-linked fashion.

A diverse spectrum of vanadium compounds have arisen, over the past years, as potential therapeutic agents for the treatment of malignancies. Poised to delineate the role of that transition metal ion in the biology of antitumor activity, vanadium complex species are classified in “families”, encompassing among others organometallic vanadocene V(C 5 H 5 ) 2 , oxidovanadium (V(IV)O)-containing compounds, binary and ternary peroxidovanadates and vanadium-peroxido-betaine complexes, and polyoxovanadate species. Their physicochemical nature reveals the structural integrity of the corresponding V(II), V(IV) and V(V) vanadoforms and exemplifies the distinct vanadium chemical reactivity patterns leading to discrete species likely to favor physiological and biochemical compatibility in a (sub)cellular environment. The ensuing analysis of the biological activity of these vanadoforms unravels specific roles for vanadium, commensurate with its physicochemical nature and properties. Invariably, it appears that vanadium suppresses growth and the spread of tumors by (a) inhibiting tumor cell proliferation and inducing apoptosis, and (b) limiting invasion and the metastatic potential of neoplastic cells. The prospect of vanadium's involvement in redox-active ROS-RNS associated apoptotic processes, interactions with miRNA, autophagy, anoikis mechanistic processes and cell differentiation capacities, individually and/or collectively contributing to the demise of cancer cells, denotes the potential of that metal ion as a future anticancer metallodrug. Concurrent consideration of both the chemical and biological attributes of the existing vanadoforms set the stage for the design and synthetic strategies leading to vanadium species aspiring to promote biological anticancer activity with effectiveness, selectivity and specificity. The molecular events associated with the advent of such vanadium compounds set the future challenges of this interdisciplinary field of bioinorganic chemistry and are expected to shape the prospect of achieving effective antitumor vanadodrugs.

Neurodegenerative diseases entail deeply complex processes, intimately associated with progressive brain damage reflecting cellular demise. Biochemical reactivity linked to such processes in Alzheimer's disease involves, among others, metal-induced oxidative stress contributing to neuronal cell death. Prominent among redox active metals inducing oxidative stress is Cu(II). Poised to develop molecular technology counteracting oxidative stress, efforts were launched to prepare bioactive hybrid nanoparticles, capable of working as host-carriers of potent antioxidants, such as the natural flavonoid quercetin. Employing synthetic protocols consistent with the assembly of silica nanoparticles, PEGylated and CTAB-modified materials were synthesized. Subsequent concentration-dependent loading of quercetin led to well-defined molecular carriers, the antioxidant efficiency of which was determined through drug release studies using UV-visible spectroscopy. The physicochemical characterization (elemental analysis, particle size, z-potential, FT-IR, thermogravimetric analysis, scanning electron microscopy) of the empty and loaded silica nanoparticles led to the formulation of optimized material linked to the delivery of the encapsulated antioxidant to primary rat hippocampal cultures under oxidative stress. Entrapment and drug release studies showed a) the competence of hybrid nanoparticles as far as the loading capacity in quercetin (concentration dependence), b) congruence with the physicochemical features determined, and c) the release profile of the nanoparticle load under oxidative stress in neuronal cultures. The bio-activity profile of quercetin nanoparticles in a neurodegenerative environment brought on by Cu(II) a) denotes the improved specificity of antioxidant reactivity counteracting oxidative stress, and b) sets the stage for the development of molecular protection and preventive medical nanotechnology of relevance to neurodegenerative Alzheimer's disease.

Efforts to probe and delineate intricate structure–property relationships key to the development of crystalline Pb(II)-containing metal–organic framework materials led to the design and pH-specific hydrothermal synthetic investigation of binary/ternary Pb(II)-(di)tricarboxylate ligand (succinic, glutaric, tricarballylic acids) systems in the presence of variable-nature aromatic N,N′-chelators bipyridine (bpy)/phenanthroline (phen). The arisen crystalline materials [Pb(phen)(suc)]n (1), [Pb3(phen)3(glu)3]n·7nH2O (2), [Pb3(tca)2]n (3), and [Pb2(phen)2(tcaH)2]n·nH2O (4) provide evidence for structural correlations linking the nature of ligands with Pb(II) chemistry and the emerging crystalline-polymeric assemblies. Detailed physicochemical characterization (Fourier transform infrared spectroscopy, 13C-,207Pb-cross polarization magic angle spinning NMR, thermogravimetric analysis, luminescence) reveals distinct architecture, lattice dimensionality (2D-3D), and luminescence property correlations and identifies...

The chemical reactivity of binary and ternary ZrIV/hydroxycarboxylic acid/(N,N-aromatic chelator) systems (hydroxycarboxylic acid = citric, malic acid; N,N-aromatic chelator = 1,10-phenanthroline) has been investigated in a pH-specific manner, giving rise to the new binary and ternary crystalline materials [Zr2F6(C6H4O7)2](CH6N3)6·H2O (1), [Zr2F6(C4H3O5)2](NH4)4·3H2O (2), [Zr2(C4H3O5)2(C4H4O5)2(C4H5O5)2](CH6N3)4·4.5H2O (3), and [Zr2(C4H3O5)2(C4H4O5)2(C4H5O5)2](C12H8N2)(C12H9N2)2(CH6N3)2·6H2O (4). Compounds 1–4 were characterized by elemental analysis, FTIR spectroscopy, TGA, 13C-CPMAS, 19F-DPMAS, and 1H CRAMPS NMR spectroscopy, and X-ray crystallography. The structures of 1–4 reveal the influence of fluoride in the starting ZrIV reagents on the identity of the Zr2O2-containing dinuclear assemblies in the arisen 3D architectures. The uniquely defined spectroscopic data, including the NMR data, corroborate the X-ray structures of 1–4 and reflect the contribution of the intra/intermolecular interactions to the structural speciation of the investigated systems. Collectively, the work 1) depicts the factors that determine the nature and properties of the emerging synthetic materials in the investigated systems, 2) formulates structural architecture–lattice dimensionality and spectroscopic fingerprint correlations, and 3) projects the framework through which new ZrIV materials with defined physicochemical properties can arise at the binary and ternary level.

In an attempt to understand the aqueous interactions of Cr(III) with low-molecular mass physiological ligands and examine its role as an adipogenic metallodrug agent in Diabetes mellitus II, the pH-specific synthesis in the binary-ternary Cr(III)-(HA = hydroxycarboxylic acid)-(N,N)-aromatic chelator (AC) (HA = 2-hydroxyethyl iminodiacetic acid/heidaH2, quinic acid; AC = 1,10-phenanthroline/phen) systems was pursued, leading to four new crystalline compounds. All materials were characterized by elemental analysis, UV–Visible, FT-IR, and ESI-MS spectroscopy, cyclic voltammetry, and X-Ray crystallography. Concurrently, the aqueous speciation of the binary Cr(III)-(2-hydroxyethyl iminodiacetic acid) system, complemented by ESI-MS, provided key-details of the species in solution correlating with the solid-state species. The structurally distinct Cr(III) soluble species were subsequently used in an in vitro investigation of their cytotoxic activity in 3T3-L1 fibroblast cultures. Compound 1 exhibited solubility, bioavailability, and atoxicity over a wide concentration range (0.1–100 μΜ) in contrast to 3, which was toxic. The adipogenic potential of 1 was subsequently investigated toward transformation of pre-adipocytes into mature adipocytes. Confirmation of that capacity relied on molecular biological techniques a) involving genes (glucose transporter type 4, peroxisome proliferator-activated receptor gamma, glucokinase, and adiponectin) serving as sensors of the transformation process, b) comparing the Cr(III)-adipogenicity potential to that of insulin, and c) exemplifying the ultimate maturity of adipocytes poised to catabolize glucose. The collective effort points out salient structural features in the coordination sphere of Cr(III) inducing adipogenic transformation relevant to combating hyperglycemia. The multiply targeted mechanistic insight into such a process exemplifies the role of well-defined Cr(III) complex forms as potential insulin-mimetic adipogenic agents in Diabetes mellitus II.

Biological systems ranging from simple ecology models to biochemical interactions in molecular biology, have profited profoundly by the advances and potentials of nanotechnology, especially those in lower dimensions. Molecular nanonetworks, the outcome of this adjacency, have been under great growth, the result of which was the establishment of molecular communication paradigm. Under this paradigm, we study the message dissemination dynamics in a biological communication system, by a model typical of electromagnetic networks. Applying a reaction-diffusion mathematical model of double diffusivity in a biological communication system, we compare the outcome with the simulation results. To this aim and based on a commercial tool, a set of efficient simulation scenarios, for the precise prediction of message dissemination dynamics were run, under the newly developed simulation framework. In particular, single and multiple sources of stimuli for different bacterial speeds and specimen geometries have been simulated. Results reveal that the message dissemination process in such bionanonetworks, can be successfully described by the reaction diffusion model, supporting the use of macro-scale simulation methods.

Naturally occurring dietary flavonoids and curcuminoids are two classes of widely spread plant secondary metabolites that have received considerable attention on account of their antiamyloidogenic, antioxidative, and anti-inflammatory properties.

In this work, we present evidence on the suitability of spin probes to report on the thermal treatment of bovine serum albumin (BSA), in the temperature range 293-343 K, and indirectly monitor the release of sodium dodecyl sulfate (SDS) from its complex with BSA using a covalent gel with β-cyclodextrin (β-CD) in the network. The spin probes used, 5- and 7-doxyl-stearic acids (5-DSA, 7-DSA) or 4-(N,N'-dimethyl-N-hexadecyl)ammonium-2,2',6,6'-tetramethylpiperidine-1-oxyl iodide (CAT16), present similar, fatty acid-like structural features. Their continuous wave electron paramagnetic resonance (CW-EPR) spectra, however, reflect different dynamics when complexed with BSA: a restricted motion for 5-DSA, almost nonsensitive to the heating/cooling cycle, and a faster temperature-dependent dynamic motion for CAT16. Molecular docking allows us to rationalize these results by revealing the different binding modes of 5-DSA and CAT16. The EPR data on the temperature effect on BSA are supported by circular dichroism results projecting recovery, upon cooling, of the initial binding ability of BSA for samples heated to 323 K. The interactions occurring in BSA/SDS/β-CD systems are investigated by CW-EPR and FT-ESEEM spectroscopies. It is found that the covalent gel containing β-CD can efficiently remove SDS from the BSA/SDS complex. The gel is not permeable to BSA but it can encapsulate SDS, thus yielding the free protein in solution and allowing recovery of the native protein conformation. Collectively, the accrued knowledge supports potential applications in protein purification biotechnological processes.

To probe and understand the structural and coordinative flexibility of Group 13 ions with α-hydroxycarboxylic acids, leading to crystalline inorganic–organic hybrid materials with distinct lattice architecture, dimensionality, and spectroscopic properties, the systematic synthesis and physicochemical properties of binary and ternary B(III), Al(III), Ga(III), In(III), and Tl(I)-benzilic acid-(phenanthroline) systems were investigated in water–alcohol mixtures. Stoichiometric reactions of Group 13 ions with benzilic acid and phenanthroline (phen) afforded the new materials [B(C14H10O3)2](C3H5N2)·H2O (1), [Al(C14H11O3)3]·0.5C2H5OH·4.5H2O (2), [Ga(C14H11O3)3]·CH3OH·3H2O (3), [In(C14H11O3)4]·C3H5N2·C2H5OH·H2O (4), [Tl(C14H11O3)]n (5), [Tl2(C14H11O3)2(phen)2] (6), and [Tl(C14H11O3)(phen)(H2O)](C14H12O3)(phen) (7). All materials were characterized by elemental analysis, Fourier transform infrared spectroscopy, 13C, 11B, 27Al, 71Ga, and 205Tl cross-polarization/magic-angle spinning NMR, thermogravimetric analysis...

The structure of the title centrosymmetric compound, [Zn(C9H6NO)2(H2O)2], has already been solved three times [Merritt, Cady & Mundy (1954).Acta Cryst.7, 473–476; Palenik (1964).Acta Cryst.17, 696–700; Chen, Zhang, Shi, Huang, Liang & Zhou (2003).Acta Cryst.E59, m814–m815]. The authors of the two most recent papers state that they attained lowerR1 values than that obtained in the 1954 paper, but they do not mention that Merrittet al.had derived the structural model from a twinned crystal. Also, from a structural point of view, there are strong indications that the most recent report is in fact the isostructural CuIIcomplex already reported by Okabe & Saishu [Acta Cryst.(2001), E57, m251–m252] and not the ZnIIcomplex. The structure of the title compound is reported here based on data obtained from a twinned crystal.

Poised to investigate the association of vanadium with physiological substrates in materials capable of exerting anticancer biological activity, pH-specific synthetic chemical reactivity between vanadium and triethyl ammonium acetate/trigonelline in aqueous and mixed organic-aqueous media led to the isolation of three new binary composite materials, namely K2[(MeN(+)C5H4COOH)2][V10O28H2]·2H2O (1), [(H2N(+)Me2)4][V10O28H2][Me3N(+)CH2COO(–)]2 (2), and [(Me3N(+)CH2COOH)4][V10O28H2][Me3N(+)CH2COO(–)]2·2H2O (3). 1–3 were characterized by elemental analysis, FT-IR and UV/Vis spectroscopy, Cyclic voltammetry, TGA-DTG, and X-ray crystallography. In all three compounds, the [V10O28H2]4– core unit is a common cluster assembly, with the vanadium in the +5 oxidation state. The counteracting cationic assembly in each composite material originates in the betaine starting reagent or the solvent out of which the materials crystallized. Biological activity studies of 1 and 3 in vitro in MCF-7 breast epithelial and A549 lung adenocarcinoma cell cultures show that both materials inhibit the viability of both cell lines in a dose-dependent fashion, in juxtaposition to the behavior of the betaine components present in these materials. Collectively, the herein studies a) reveal the uniquely defined synthetic methodologies and physicochemical properties of the variably assembled [V10O28H2]4– core units crystallized into the composite binary polyoxovanadate-betaine lattice structures, b) unravel the distinct cytotoxicity profile of the composite materials toward MCF-7 and A549 cells, and c) attest to their future potential as metallodrugs of pharmacological significance in anticancer activity.