Bithiophene-Functionalized Infrared Two-Photon Absorption Metal Complexes as Single-Molecule Platforms for Synergistic Photodynamic, Photothermal, and Chemotherapy.

A planar conjugated ligand functionalized with bithiophene and its Ru(II), Os(II), and Ir(III) complexes have been constructed as single-molecule platform for synergistic photodynamic, photothermal, and chemotherapy. The complexes have significant two-photon absorption at 808 nm and remarkable singlet oxygen and superoxide anion production in aqueous solution and cells when exposed to 808 nm infrared irradiation. The most potent Ru(II) complex Ru7 enters tumor cells via the rare macropinocytosis, locates in both nuclei and mitochondria, and regulates DNA-related chemotherapeutic mechanisms intranuclearly including DNA topoisomerase and RNA polymerase inhibition and their synergistic effects with photoactivated apoptosis, ferroptosis and DNA cleavage. Ru7 exhibits high efficacy in vivo for malignant melanoma and cisplatin-resistant non-small cell lung cancer tumors, with a 100 % survival rate of mice, low toxicity to normal cells and low residual rate. Such an infrared two-photon activatable metal complex may contribute to a new generation of single-molecule-based integrated diagnosis and treatment platform to address drug resistance in clinical practice and phototherapy for large, deeply located solid tumors.

A Photodynamic and Photochemotherapeutic Platinum-Iridium Charge-Transfer Conjugate for Anticancer Therapy.

The novel hetero-dinuclear complex trans,trans,trans-[PtIV(py)2(N3)2(OH)(µ-OOCCH2CH2CONHCH2-bpyMe)IrIII(ppy)2]Cl (Pt-Ir), exhibits charge transfer between the acceptor photochemotherapeutic Pt(IV) (Pt-OH) and donor photodynamic Ir(III) (Ir-NH2) fragments. It is stable in the dark, but undergoes photodecomposition more rapidly than the Pt(IV) parent complex (Pt-OH) to generate Pt(II) species, an azidyl radical and 1O2. The Ir(III)* excited state, formed after irradiation, can oxidise NADH to NAD⋅ radicals and NAD+. Pt-Ir is highly photocytotoxic towards cancer cells with a high photocytotoxicity index upon irradiation with blue light (465 nm, 4.8 mW/cm2), even with short light-exposure times (10-60 min). In contrast, the mononuclear Pt-OH and Ir-NH2 subunits and their simple mixture are much less potent. Cellular Pt accumulation was higher for Pt-Ir compared to Pt-OH. Irradiation of Pt-Ir in cancer cells damages nuclei and releases chromosomes. Synchrotron-XRF revealed ca. 4× higher levels of intracellular platinum compared to iridium in Pt-Ir treated cells under dark conditions. Luminescent Pt-Ir distributes over the whole cell and generates ROS and 1O2 within 1 h of irradiation. Iridium localises strongly in small compartments, suggestive of complex cleavage and excretion via recycling vesicles (e.g. lysosomes). The combination of PDT and PACT motifs in one molecule, provides Pt-Ir with a novel strategy for multimodal phototherapy.

Unveiling the promising anticancer effect of copper-based compounds: a comprehensive review.

Copper is a necessary micronutrient for maintaining the well-being of the human body. The biological activity of organic ligands, especially their anticancer activity, is often enhanced when they coordinate with copper(I) and (II) ions. Copper and its compounds are capable of inducing tumor cell death through various mechanisms of action, including activation of apoptosis signaling pathways by reactive oxygen species (ROS), inhibition of angiogenesis, induction of cuproptosis, and paraptosis. Some of the copper complexes are currently being evaluated in clinical trials for their ability to map tumor hypoxia in various cancers, including locally advanced rectal cancer and bulky tumors. Several studies have shown that copper nanoparticles can be used as effective agents in chemodynamic therapy, phototherapy, hyperthermia, and immunotherapy. Despite the promising anticancer activity of copper-based compounds, their use in clinical trials is subject to certain limitations. Elevated copper concentrations may promote tumor growth, angiogenesis, and metastasis by affecting cellular processes.

Photoactivatable, mitochondria targeting dppz iridium(III) complex selectively interacts and damages mitochondrial DNA in cancer cells.

Cyclometalated Ir(III) complex [Ir(L)2(dppz)]PF6 (where L = 1-methyl-2-(thiophen-2-yl)-1H-benzo[d]imidazole and dppz = dipyrido [3,2-a:2',3'-c]phenazine) (Ir1) is potent anticancer agent whose potency can be significantly increased by irradiation with blue light. Structural features of the cyclometalated Ir(III) complex Ir1 investigated in this work, particularly the presence of dppz ligand possessing an extended planar area, suggest that this complex could interact with DNA. Here, we have shown that Ir1 accumulates predominantly in mitochondria of cancer cells where effectively and selectively binds mitochondrial (mt)DNA. Additionally, the results demonstrated that Ir1 effectively suppresses transcription of mitochondria-encoded genes, especially after irradiation, which may further affect mitochondrial (and thus also cellular) functions. The observation that Ir1 binds selectively to mtDNA implies that the mechanism of its biological activity in cancer cells may also be connected with its interaction and damage to mtDNA. Further investigations revealed that Ir1 tightly binds DNA in a cell-free environment, with sequence preference for GC over AT base pairs. Although the dppz ligand itself or as a ligand in structurally similar DNA-intercalating Ru polypyridine complexes based on dppz ligand intercalates into DNA, the DNA binding mode of Ir1 comprises surprisingly a groove binding rather than an intercalation. Also interestingly, after irradiation with visible (blue) light, Ir1 was capable of cleaving DNA, likely due to the production of superoxide anion radical. The results of this study show that mtDNA damage by Ir1 plays a significant role in its mechanism of antitumor efficacy. In addition, the results of this work are consistent with the hypothesis and support the view that targeting the mitochondrial genome is an effective strategy for anticancer (photo)therapy and that the class of photoactivatable dipyridophenazine Ir(III) compounds may represent prospective substances suitable for further testing.

Influence of the modification of the cosmetic peptide Argireline on the affinity toward copper(II) ions.

Argireline (Ac-EEMQRR-NH2 ), a well-known neurotransmitter peptide with a potency similar to botulinum neurotoxins, reveals a proven affinity toward Cu(II) ions. We report herein Cu(II) chelating properties of three new Argireline derivatives, namely, AN4 (Ac-EAHRR-NH2 ), AN5 (Ac-EEHQRR-NH2 ), and AN6 (Ac-EAHQRK-NH2 ). Two complementary experimental techniques, i.e., potentiometric titration (PT) and isothermal titration calorimetry (ITC), have been employed to describe the acid-base properties of the investigated peptides as well as the thermodynamic parameters of the Cu(II) complex formation. Additionally, based on density functional theory (DFT) calculations, we propose the most likely structures of the resulting Cu-peptide complexes. Finally, the cytotoxicity of the free peptides and the corresponding Cu(II) complexes was estimated in human skin cells for their possible future cosmetic application. The biological results were subsequently compared with free Argireline, its Cu(II)-complexes, and the previously studied AN2 derivative (EAHQRR).

Antibacterial Photodynamic Therapy by Zn(II)-Curcumin Complex: Synthesis, Characterization, DFT Calculation, Antibacterial Activity, and Molecular Docking.

The increase in antibacterial drug resistance is threatening global health conditions. Recently, antibacterial photodynamic therapy (aPDT) has emerged as an effective antibacterial treatment with high cure gain. In this work, three Zn(II) complexes viz., [Zn(en)(acac)Cl] (1), [Zn(bpy)(acac)Cl] (2), [Zn(en)(cur)Cl] (3), where en=ethylenediamine (1 and 3), bpy=2,2'-bipyridine (2), acac=acetylacetonate (1 and 2), cur=curcumin monoanionic (3) were developed as aPDT agents. Complexes 1-3 were synthesized and fully characterized using NMR, HRMS, FTIR, UV-Vis. and fluorescence spectroscopy. The HOMO-LUMO energy gap (Eg), and adiabatic splittings (ΔS1-T1 and ΔS0-T1 ) obtained from DFT calculation indicated the photosensivity of the complexes. These complexes have not shown any potent antibacterial activity under dark conditions but the antibacterial activity of these complexes was significantly enhanced upon light exposure (MIC value up to 0.025 µg/mL) due to their light-mediated 1 O2 generation abilities. The molecular docking study suggested that complexes 1-3 interact efficiently with DNA gyrase B (PDB ID: 4uro). Importantly, 1-3 did not show any toxicity toward normal HEK-293 cells. Overall, in this work, we have demonstrated the promising potential of Zn(II) complexes as effective antibacterial agents under the influence of visible light.

Cyclometalated Ir(III) theranostic molecular probe enabled mitochondria targeted fluorescence-SERS-guided phototherapy in breast cancer cells.

The increased energy demands inherent in cancer cells necessitate a dependence on mitochondrial assistance for their proliferation and metastatic activity. Herein, an innovative photo-medical approach has been attempted, specifically targeting mitochondria, the cellular powerhouses, to attain therapeutic benefit. This strategy facilitates the rapid and precise initiation of apoptosis, the programmed cell death process. In this goal, we have synthesized cyclometalated Iridium (III) molecular probes, denoted as Ir-CN and Ir-H, with a nitrile (CN) and a hydrogen-functionalized bipyridine as ancillary ligands, respectively. Ir-CN has shown superior photosensitizing properties and lower dark cytotoxicity compared to Ir-H in the breast cancer cell line MCF-7, positioning it as the preferred probe for photodynamic therapy (PDT). The synthesized Ir-CN induces alterations in mitochondrial membrane potential, disrupting the respiratory chain function, and generating reactive oxygen species that activate signaling pathways leading to cell death. The CN-conjugated bipyridine ligand in Ir-CN contributes to the intense red fluorescence and the positive charge on the central metal atom facilitates specific mitochondrial colocalization (colocalization coefficient of 0.90). Together with this, the Iridium metal, with strong spin-orbit coupling, efficiently generates singlet oxygen with a quantum yield of 0.79. Consequently, the cytotoxic singlet oxygen produced by Ir-CN upon laser exposure disrupts mitochondrial processes, arresting the electron transport chain and energy production, ultimately leading to programmed cell death. This mitochondrial imbalance and apoptotic induction were dually confirmed through various apoptotic assays including Annexin V staining and by mapping the molecular level changes through surface-enhanced Raman spectroscopy (SERS). Therefore, cyclometalated Ir-CN emerges as a promising molecular probe for cancer theranostics, inducing laser-assisted mitochondrial damage, as tracked through bimodal fluorescence and SERS.

Comparison of deep eutectic solvent-based ultrasound- and heat-assisted extraction of bioactive compounds from Withania somnifera and process optimization using response surface methodology.

Extraction of bioactive compounds from Withania somnifera roots was studied using sodium acetate-glycerol deep eutectic solvent (DES) and two techniques ultrasound-assisted extraction (UAE) and heat-assisted extraction (HAE) under response surface methodology (RSM). For UAE and HAE, total phenolic content (TPC, mg gallic acid equivalents per g dry weight (mg GAE g-1 DW)), total flavonoid content (TFC, mg rutin equivalents g-1 DW (mg RE g-1 DW)), radical scavenging activity (RSA, mg AAE (ascorbic acid equivalents) g-1 DW), and iron chelating activity (ICA, mg EDTAE (ethylenediaminetetraacetate equivalents) g-1 DW%) were 6.51, 6.08, 12.56, and 3.57, respectively, and 3.33, 3.98. 6.57 and 2.48, respectively. For UAE, the optimal conditions were a DES concentration of 50 %, temperature of 60 °C, and time of 20 min, and for HAE, a DES concentration of 60 %, temperature of 60 °C, and time of 75 min. The discovered models were strongly supported by the validation experiments. UAE was more efficient and less time-consuming for extracting phytoconstituents of the W. somnifera than HAE.

Ruthenium(II)-Arene Curcuminoid Complexes as Photosensitizer Agents for Antineoplastic and Antimicrobial Photodynamic Therapy: In Vitro and In Vivo Insights.

Photodynamic therapy (PDT) is an anticancer/antibacterial strategy in which photosensitizers (PSs), light, and molecular oxygen generate reactive oxygen species and induce cell death. PDT presents greater selectivity towards tumor cells than conventional chemotherapy; however, PSs have limitations that have prompted the search for new molecules featuring more favorable chemical-physical characteristics. Curcumin and its derivatives have been used in PDT. However, low water solubility, rapid metabolism, interference with other drugs, and low stability limit curcumin use. Chemical modifications have been proposed to improve curcumin activity, and metal-based PSs, especially ruthenium(II) complexes, have attracted considerable attention. This study aimed to characterize six Ru(II)-arene curcuminoids for anticancer and/or antibacterial PDT. The hydrophilicity, photodegradation rates, and singlet oxygen generation of the compounds were evaluated. The photodynamic effects on human colorectal cancer cell lines were also assessed, along with the ability of the compounds to induce ROS production, apoptotic, necrotic, and/or autophagic cell death. Overall, our encouraging results indicate that the Ru(II)-arene curcuminoid derivatives are worthy of further investigation and could represent an interesting option for cancer PDT. Additionally, the lack of significant in vivo toxicity on the larvae of Galleria mellonella is an important finding. Finally, the photoantimicrobial activity of HCurc I against Gram-positive bacteria is indeed promising.

Red-Light-Responsive Polypeptoid Nanoassemblies Containing a Ruthenium(II) Polypyridyl Complex with Synergistically Enhanced Drug Release and ROS Generation for Anticancer Phototherapy.

Polymer micelles/vesicles made of a red-light-responsive Ru(II)-containing block copolymer (PolyRu) are elaborated as a model system for anticancer phototherapy. PolyRu is composed of PEG and a hydrophobic polypeptoid bearing thioether side chains, 40% of which are coordinated with [Ru(2,2':6',2″-terpyridine)(2,2'-biquinoline)](PF6)2 via the Ru-S bond, resulting in a 67 wt % Ru complex loading capacity. Red-light illumination induces the photocleavage of the Ru-S bond and produces [Ru(2,2':6',2″-terpyridine)(2,2'-biquinoline)(H2O)](PF6)2. Meanwhile, ROS are generated under the photosensitization of the Ru complex and oxidize hydrophobic thioether to hydrophilic sulfoxide, causing the disruption of micelles/vesicles. During the disruption, ROS generation and Ru complex release are synergistically enhanced. PolyRu micelles/vesicles are taken up by cancer cells while they exhibit very low cytotoxicity in the dark. In contrast, they show much higher cytotoxicity under red-light irradiation. PolyRu micelles/vesicles are promising nanoassembly prototypes that protect metallodrugs in the dark but exhibit light-activated anticancer effects with spatiotemporal control for photoactivated chemotherapy and photodynamic therapy.

Development of Ruthenium Nanophotocages with Red or Near-Infrared Light-Responsiveness.

The development of light-triggered ruthenium (Ru) nanophotocages has revolutionized conventional methods of drug administration, thereby facilitating cancer therapy in a noninvasive and temperate manner. Ru nanophotocages employ a distinct approach known as photoactivated chemotherapy (PACT), wherein light-induced ligand dissociation yields a toxic metal complex or a ligand capable of performing other functions such as optically controlled protein degradation and drug delivery. Simultaneously, this process is accompanied by the generation of reactive oxygen species (ROS), which serve as an effective anticancer agent in combination with PACT and photodynamic therapy (PDT). Due to its exceptional attributes of extended tissue penetration, and minimized tissue damage, red light or near-infrared light is widely acknowledged as the "phototherapeutic window" (650-900 nm). In this Concept, we present an overview of the most recent advancements in Ru nanophotocages within the phototherapeutic range. Diverse aspects, including design principles, photocaging efficacy, photoactivation mechanisms, and potential applications in the field of biomedical chemistry, are discussed. Questions and challenges regarding their synthesis, characterization, and applications are also discussed. This Concept would foster further exploration into the realm of Ru nanophotocages.

Recent advances on the construction of long-wavelength emissive supramolecular coordination complexes for photo-diagnosis and therapy.

Recently, metal-based drugs have attracted relentless interest in the biomedical field. However, their short excitation/emission wavelengths and unsatisfactory therapeutic efficiency limit their biological applications in vivo. Currently, the second near-infrared window (NIR-II, 1000-1700 nm) provides more accurate imaging and therapeutic options. Thus, there has been a constant focus on developing multifunctional NIR metal agents for imaging and therapy that have deeper tissue penetration. Fortunately, supramolecular coordination complexes (SCCs) formed by the coordination-driven self-assembly of NIR-II emissive ligands can address the above issues. Importantly, metal receptors with chemotherapeutic properties in SCCs can bind to luminescent ligands, thus becoming a versatile therapeutic platform for chemotherapy, imaging and phototherapy. In this context, we systematically summarize the evolution of NIR-II emissive SCCs for biomedical applications and discuss future challenges and prospects.

Novel Ru(II) complexes with multiple anticancer photoreactivity: ligand exchange, photoredox catalysis, reactive oxygen generation and endoperoxide formation.

The hypoxic microenvironment and drug resistance of cancer cells have become a huge threat for clinical anticancer therapy. Anticancer phototherapy providing spatial and temporal control over drug activation may conquer this problem. Herein, we report a novel photoactivated Ru(II) complex (Ru2) with multiple activities including photochemotherapy, photodynamic and photocatalytic therapy, and endoperoxide formation. Upon white light irradiation, Ru2 can dissociate the coordinating ligands and form endoperoxides, produce diverse reactive oxygen species and catalytically oxidize cellular coenzymes. As a result, Ru2 shows promising antiproliferation activity toward cisplatin and 5-fluorouracil resistant tumor cell lines under normoxia and hypoxia. The multifunctional design strategy of metal-based anticancer drugs offers novel efficient therapeutics to combat drug-resistant cancer cells under hypoxia.

Anticancer activity of Ni(II) and Zn(II) complexes based on new unsymmetrical salophen-type ligands: synthesis, characterization and single-crystal X-ray diffraction.

The discovery of new coordination compounds with anticancer properties is an active field of research due to the severe side effects of platinum-based compounds currently used in chemotherapy. In the search for new agents for the treatment of cancer, unsymmetrical N2O2-tetradentate ligand (H2L1 and H2L2) and their Ni(II) and Zn(II) asymmetric complexes (NiII-L1-2 and ZnII-L1-2) have been synthesized and fully characterized. 1H NMR studies revealed that the ligands and complexes were stable in mixtures of DMSO : D2O (9 : 1). Complementary UV-Vis studies confirmed that ZnII derivatives also exhibit high stability in mixtures DMSO : buffer (6 : 4) after 24 h. Single-crystal X-ray diffraction studies confirmed the molecular structures of H2L1, H2L2, NiII-L1, and NiII-L2. At the molecular level, complexes were completely planar without significant distortions of the square-planar geometry according to τ4 parameter. Furthermore, the crystalline structures revealed non-classical intermolecular interactions of the C-H⋯O and the Ni⋯Ni type. The ligands and complexes were screened against the human osteosarcoma (MG-63), human colon cancer (HCT-116), breast cancer (MDA-MB-231) cell lines, and non-cancerous cells (L929). H2L1 and H2L2 ligands not caused cytotoxic effects at a concentration of 100 µM, while NiII-L2, ZnII-L1, and ZnII-L2 complexes induce cytotoxic effects in all cell lines. NiII-L2 was a more active complex against MG-63 (3.9 ± 1.5) and HCT-116 (3.4 ± 1.7) cell lines with IC50 values in the low micromolar range. In addition, this compound was 10-, 5-, and 11-fold more potent than cisplatin in MG-63 (39 ± 1.8), HCT-116 (17.2), and MDA-MB-231 (131 ± 18), respectively. Three complexes exhibited great selectivity for tumoral cells with SI values ranging from 1.6 to 7.4.

Accessing parity-forbidden d-d transitions for photocatalytic CO2 reduction driven by infrared light.

A general approach to promote IR light-driven CO2 reduction within ultrathin Cu-based hydrotalcite-like hydroxy salts is presented. Associated band structures and optical properties of the Cu-based materials are first predicted by theory. Subsequently, Cu4(SO4)(OH)6 nanosheets were synthesized and are found to undergo cascaded electron transfer processes based on d-d orbital transitions under infrared light irradiation. The obtained samples exhibit excellent activity for IR light-driven CO2 reduction, with a production rate of 21.95 and 4.11 µmol g-1 h-1 for CO and CH4, respectively, surpassing most reported catalysts under the same reaction conditions. X-ray absorption spectroscopy and in situ Fourier-transform infrared spectroscopy are used to track the evolution of the catalytic sites and intermediates to understand the photocatalytic mechanism. Similar ultrathin catalysts are also investigated to explore the generality of the proposed electron transfer approach. Our findings illustrate that abundant transition metal complexes hold great promise for IR light-responsive photocatalysis.

NMR and EPR study of the interaction of tris(3-hydroxy-4-pyridinonato) Ga(III) complexes with liposomes that mimic plant membranes.

We performed an NMR and EPR study of the interaction of four [Ga(3,4-HPO)3] chelates with liposomes derived from a soybean extract (SEL) and simpler formulations using POPC (100%) and POPE:POPC (50%). Parent [Fe(3,4-HPO)3] chelates are eligible to prevent Iron Deficiency Chlorosis and we took advantage of the likenesses of the ions Fe (III) and Ga (III), and the fact their metal ion complexes are isostructural, to perform a combined NMR and EPR study to get information about the permeation properties of the complexes. The results demonstrate the presence of liposomes loaded with Ga-chelates and that the distribution of complexes alongside the bilayer is dependent on their structure. Two compounds, [Ga(mpp)3] and [Ga(etpp)3], have a higher affinity for the polar region of the liposome bilayer thus suggesting that their structure facilitates their permanence at the root-rhizosphere interface. Chelates [Ga(dmpp)3] and [Ga(mrb13)3] interact with all types of protons of the lipid bilayer thus implying that they travel all along the bilayer structure indicating their higher permeation properties through soybean membranes. The results obtained for compound, [Ga(mrb13)3], which has been included in this work but was not yet tested in plant supplementation experiments, encourage its testing in in vivo plant studies once this study revealed that it interacts strongly with the model membranes. If the results of the future experiments in plants are positive and consistent with the present membrane-interaction studies the latter could constitute a good screening test for future compounds thus saving reagents and time.

Synthesis and biological evaluation of ruthenium complexes containing phenylseleny against Gram-positive bacterial infection by damage membrane integrity and avoid drug-resistance.

Compounds modified with selenium atom as potential antibacterial agents have been exploited to combat the nondrug-resistant bacterial infection. In this study, we designed and synthesized four ruthenium complexes retouching of selenium-ether. Fortunately, those four ruthenium complexes shown excellent antibacterial bioactive (MIC: 1.56-6.25 µg/mL) against Staphylococcus aureus (S. aureus), and the most active complex Ru(II)-4 could kill S. aureus by targeting the membrane integrity and avoid the bacteria to evolve drug resistance. Moreover, Ru(II)-4 was found to significantly inhibit the formation of biofilms and biofilm eradicate capacity. In toxicity experiments, Ru(II)-4 exhibited poor hemolysis and low mammalian toxicity. To illustrate the antibacterial mechanism: we conducted scanning electron microscope (SEM), fluorescent staining, membrane rupture and DNA leakage assays. Those results demonstrated that Ru(II)-4 could destroy the integrity of bacterial cell membrane. Furthermore, both G. mellonella wax worms infection model and mouse skin infection model were established to evaluate the antibacterial activity of Ru(II)-4 in vivo, the results indicated that Ru(II)-4 was a potential candidate for combating S. aureus infections, and almost non-toxic to mouse tissue. Thus, all the results indicated that introducing selenium-atom into ruthenium compounds were a promising strategy for developing interesting antibacterial agents.

Intelligent films of marine polysaccharides and purple cauliflower extract for food packaging and spoilage monitoring.

In this study, metalloanthocyanin-inspired, biodegradable packaging films were developed by incorporating purple cauliflower extracted (PCE) anthocyanins into alginate (AL)/carboxymethyl chitosan (CCS) hybrid polymer matrices based on complexation of metal ions with these marine polysaccharides and anthocyanins. PCE anthocyanins-incorporated AL/CCS films were further modified with fucoidan (FD) because this sulfated polysaccharide can form strong interactions with anthocyanins. Metals-involved complexation (Ca2+ and Zn2+-crosslinked films) improved the mechanical strength and water vapor permeability but reduced the swelling degree of the films. Zn2+-cross-linked films exhibited significantly higher antibacterial activity than did pristine (non-crosslinked) and Ca2+-cross-linked films. The metal ion/polysaccharide-involved complexation with anthocyanin reduced the release rate of anthocyanins, increased the storage stability and antioxidant capability, and improved the sensitivity of the colorimetric response of the indicator films for monitoring the freshness of shrimp. The anthocyanin-metal-polysaccharide complex film showed great potential as active and intelligent packaging of food products.

Ferric Pyrophosphate Forms Soluble Iron Coordination Complexes with Zinc Compounds and Solubilizing Agents in Extruded Rice and Predicts Increased Iron Solubility and Bioavailability in Young Women.

BACKGROUND: Co-extrusion of ferric pyrophosphate (FePP) with solubilizers, citric acid/trisodium citrate (CA/TSC), or ethylenediaminetetraacetic acid (EDTA) sharply increases iron absorption. Whether this can protect against the inhibition of iron absorption by phytic acid (PA) is unclear. Sodium pyrophosphate (NaPP) may be a new enhancer of iron absorption from FePP. OBJECTIVES: Our objectives were to 1) investigate the ligand coordination of iron, zinc, and solubilizers in extruded rice and test associations with iron solubility and absorption, 2) assess whether co-extrusion of FePP + CA/TSC rice can protect against inhibition of iron absorption by PA; 3) determine the effect of zinc oxide (ZnO) compared with zinc sulfate (ZnSO4), and 4) quantify iron absorption from FePP + NaPP rice. METHODS: We produced labeled 57FePP rice cofortified with ZnSO4 and EDTA, CA/TSC or NaPP, and FePP + EDTA rice with ZnO. We used electron paramagnetic resonance (EPR) to characterize iron-ligand complexes. We measured in vitro iron solubility and fractional iron absorption (FIA) in young women (n = 21, age: 22 ± 2 y, BMI: 21.3 ± 1.5 kg/m2 geometric mean plasma ferritin, 28.5 µg/L) compared with ferrous sulfate (58FeSO4). FIA was compared by linear mixed-effect model analysis. RESULTS: The addition of zinc and solubilizers created new iron coordination complexes of Fe(III) species with a weak ligand field at a high-spin state that correlated with solubility (r2 = 0.50, P = 0.02) and absorption (r2 = 0.72, P = 0.02). Phytic acid reduced FIA from FePP + CA/TSC rice by 50% (P < 0.001), to the same extent as FeSO4. FIA from FePP + EDTA + ZnO and FePP + EDTA + ZnSO4 rice did not significantly differ. Mean FIAs from FePP + EDTA + ZnSO4, FePP + CA/TSC + ZnSO4, and FePP + NaPP + ZnSO4 rice were 9% to 11% and did not significantly differ from each other or from FeSO4. CONCLUSION: Rice extrusion of FePP with solubilizers resulted in bioavailable iron coordination complexes. In the case of FePP + CA/TSC, PA exerted similar inhibition of FIA as with FeSO4. FePP + NaPP could be a further viable solubilizing agent for rice fortification. This study was registered at clinicaltrials.gov as NCT03703739.

Rescue effect of curcumin against copper toxicity.

Turmeric has long been used not only as an indispensable part of Asian cuisine but as a medicinal herb for dressing wounds, bites, burns, treating eye infections and acne. Curcuminoids are the active substances and their synthetic derivatives (i.e. diacetylcurcumin (DAC) and metal-curcumin complexes) possess an incredibly wide range of medicinal properties that encompass chelation capacity for multiple heavy metals, antioxidant activity, anti-inflammatory properties, cytotoxicity against cancerous cells, antiviral and antibacterial effects, antihypertensive and insulin sensitizing role, and regulatory role on apoptosis. The aforementioned properties have put curcumin on spotlight as a potential treatment for ailments such as, hepatic diseases, neurodegenerative diseases, metabolic syndrome, dyslipidemia, cardiovascular disease, auto-immune diseases, malignancies and conditions associated with metal overload. Copper is essential for major biological functions, however, an excess causes chronic ailments including neurodegenerative disorders. The fascinating approach of curcumin could alleviate such effect by forming a complex. Thus, this review aims to present available data on the effect of copper-curcumin interaction in various in vitro, ex-vivo in vivo, and clinical studies.