Metals/bisulfite system involved generation of 24-sulfonic-25-ene ginsenoside Rg1, a potential quality control marker for sulfur-fumigated ginseng.

Ginseng is a most popular health-promoting food with ginsenosides as its main bioactive ingredients. Illegal sulfur-fumigation causes ginsenosides convert to toxic sulfur-containing derivatives, and reduced the efficacy/safety of ginseng. 24-sulfo-25-ene ginsenoside Rg1 (25-ene SRg1), one of the sulfur-containing derivatives, is a potential quality control marker of fumigated ginseng, but with low accessibility owing to its unknown generation mechanism. In this study, metals/bisulfite system involved generation mechanism was investigated and verified. The generation of 25-ene SRg1 in sulfur-fumigated ginseng is that SO2, formed during sulfur-fumigation, reacted with water and ionized into HSO3-. On the one hand, under the metals/bisulfite system, HSO3- generates HSO5- and free radicals which converted ginsenoside Rg1 to 24,25-epoxide Rg1; on the other hand, as a nucleophilic group, HSO3- reacted with 24,25-epoxide Rg1 and further dehydrated to 25-ene SRg1. This study provided a technical support for the promotion of 25-ene SRg1 as the characteristic quality control marker of sulfur-fumigated ginseng.

A critical review of a typical research system for food-derived metal-chelating peptides: Production, characterization, identification, digestion, and absorption.

In the past decade, food-derived metal-chelating peptides (MCPs) have attracted significant attention from researchers working towards the prevention of metal (viz., iron, zinc, and calcium) deficiency phenomenon by primarily inhibiting the precipitation of metals caused by the gastrointestinal environment and exogenous substances (including phytic and oxalic acids). However, for the improvement of limits of current knowledge foundations and future investigation directions of MCP or their derivatives, several review categories should be improved and emphasized. The species' uniqueness and differences in MCP productions highly contribute to the different values of chelating ability with particular metal ions, whereas comprehensive reviews of chelation characterization determined by various kinds of technique support different horizons for explaining the chelation and offer options for the selection of characterization methods. The reviews of chelation mechanism clearly demonstrate the involvement of potential groups and atoms in chelating metal ions. The discussions of digestive stability and absorption in various kinds of absorption model in vitro and in vivo as well as the theory of involved cellular absorption channels and pathways are systematically reviewed and highlighted compared with previous reports as well. Meanwhile, the chelation mechanism on the molecular docking level, the binding mechanism in amino acid identification level, the utilizations of everted rat gut sac model for absorption, and the involvement of cellular absorption channels and pathway are strongly recommended as novelty in this review. This review makes a novel contribution to the literature by the comprehensive prospects for the research and development of food-derived mineral supplements.

Transition Metal Ion FRET-Based Probe to Study Cu(II)-Mediated Amyloid-ß Ligand Binding.

Recent therapeutic strategies suggest that small peptides can act as aggregation inhibitors of monomeric amyloid-ß (Αß) by inducing structural rearrangements upon complexation. However, characterizing the binding events in such dynamic and transient noncovalent complexes, especially in the presence of natively occurring metal ions, remains a challenge. Here, we deploy a combined transition metal ion Förster resonance energy transfer (tmFRET) and native ion mobility-mass spectrometry (IM-MS) approach to characterize the structure of mass- and charge-selected Aß complexes with Cu(II) ions (a quencher) and a potential aggregation inhibitor, a small neuropeptide named leucine enkephalin (LE). We show conformational changes of monomeric Αß species upon Cu(II)-binding, indicating an uncoiled N-terminus and a close interaction between the C-terminus and the central hydrophobic region. Furthermore, we introduce LE labeled at the N-terminus with a metal-chelating agent, nitrilotriacetic acid (NTA). This allows us to employ tmFRET to probe the binding even in low-abundance and transient Aß-inhibitor-metal ion complexes. Complementary intramolecular distance and global shape information from tmFRET and native IM-MS, respectively, confirmed Cu(II) displacement toward the N-terminus of Αß, which discloses the binding region and the inhibitor's orientation.

Impact of internal metal ions in tea polysaccharides on antioxidant potential and suppression of cancer cell growth.

Four kinds of tea polysaccharides (MBTPS, MGTPS, ZBTPS, ZGTPS) were extracted from Maofeng black tea, Maofeng green tea,Ziyan black tea and Ziyan green tea, and then four tea polysaccharides (RMBTPS, RMGTPS, RZBTPS, RZGTPS) after metal removal were prepared. The physicochemical properties, antioxidant activity and inhibitory activity on cancer cell proliferation of the above polysaccharides were studied. The composition analysis shows that these tea polysaccharides were glycoproteins complexes, composed of a variety of monosaccharides, and the removal of metal ions did not lead to fundamental changes in the composition of polysaccharides. In vitro activity, after removing metal ions, the ABTS free radicals scavenging ability and reducing power of tea polysaccharides were decreased, and the inhibitory effect on proliferation of H22 cells weakened. There was a great correlation between metal elements Al and Ni and biological activity. The results showed that the metal ions in tea polysaccharides, especially Al and Ni, had positive effects on biological activity.

Enhancing bauxite residue properties for plant growth: Gypsum and organic amendment effects on chemical properties of soil and leachate.

Here, we assess the effects of gypsum and local organic waste as amendments to non-weathered, filter-pressed bauxite residue (BR) to improve its properties and support plant growth. In addition, we monitored the leachate quality of the amended BR under progressive leaching that simulated precipitation conditions in Northern Brazil. Free-draining column tests consisting of BR amended with gypsum and organic waste, at 5% and 10% w/w, respectively, were leached for 8 weeks to assess the effects on the chemical composition of BR and the leachates. Adding gypsum to BR reduced the exchangeable sodium (Na) percentage (ESP) from approximately 79%-48%, whereas adding only organic waste had smaller effects on ESP (from ∼79% to âˆ¼ 70%). The mean leachate pH ranged from 8.7 to 9.4 for the gypsum, and organic waste amended BR, while this was 10.3 in the leachate of the unamended BR. The treatments had similar trends of electrical conductivity throughout the experiments and were below 2 dS/cm after 8 weeks, when ∼1.700 mm simulated precipitation had leached. Aluminium (Al), Arsenic (As), and Vanadium (V) concentrations in leachates of BR with gypsum, either alone or in combination with organic waste, were significantly lowered than in leachate of non-amended BR. By contrast, metal concentrations increased if organic waste was added to BR. We conclude that amending BR with gypsum, in combination with organic waste, significantly improves the chemical properties of the solid phase and achieved rehabilitation goals for SAR and EC of the leachates after 8 weeks of leaching. However, despite high leaching rates, rehabilitation goals for pH and ESP were not achieved with gypsum either alone or combined with organic waste.

Analytical Investigation of Iron-Based Stains on Carbonate Stones: Rust Formation, Diffusion Mechanisms, and Speciation.

In cultural heritage, unaesthetic stains on carbonate stones due to their close contacts with metals are of concern for the preservation of sculptures, monumental facades and archeological finds of various origin and antiquities. Rust stains made up of various oxidized iron compounds are the most frequent forms of alteration. The presence of ferric iron on rust-stained marble surfaces was confirmed in previous studies and oriented the choice of the best cleaning method (based on complexing agents specific for ferric ions). However, the composition of rust stains may vary along their extension. As the corrosion of the metallic iron proceeds, if the oxygen levels in the surroundings are low and there are no conditions to favor the oxidation, ferrous ions can also diffuse within the carbonate structure and form a variety of intermediate compounds. In this study, the iron stains on archeological marbles were compared with those artificially produced on Carrara marbles and Travertine samples. The use of integrated techniques (optical and scanning electron microscopy as well as Mössbauer and XPS spectroscopy) with complementary analytical depths, has provided the overall information. Rust formation and diffusion mechanisms in carbonates were revealed together with the evolution of iron speciation and identification of phases such as ferrihydrite, goethite, maghemite, nanomagnetite, and hematite.

Heteropolysaccharides in sustainable corrosion inhibition: 4E (Energy, Economy, Ecology, and Effectivity) dimensions.

Carbohydrate polymers (polysaccharides) and their derivatives are widely utilized in sustainable corrosion inhibition (SCI) because of their various fascinating properties including multiple adsorption sites, high solubility and high efficiency. Contrary to traditional synthetic polymer-based corrosion inhibitors, polysaccharides are related to the 4E dimension, which stands for Energy, Economy, Ecology, and Effectivity. Furthermore, they are relatively more environmentally benign, biodegradable, and non-bioaccumulative. The current review describes the SCI features of various heteropolysaccharides, including gum Arabic (GA), glycosaminoglycans (chondroitin-4-sulfate (CS), hyaluronic acid (HA), heparin, etc.), pectin, alginates, and agar for the first time. They demonstrate impressive anticorrosive activity for different metals and alloys in a variety of corrosive electrolytes. Through their adsorption at the metal/electrolyte interface, heteropolysaccharides function by producing a corrosion-protective film. In general, their adsorption follows the Langmuir isotherm model. In their molecular structures, heteropolysaccharides contain several polar functional groups like -OH, -NH2, -COCH3, -CH2OH, cyclic and bridging O, -CH2SO3H, -SO3OH, -COOH, -NHCOCH3, -OHOR, etc. that serve as adsorption centers when they bind to metallic surfaces.

Influence of sediment quality and microbial community on the functioning capacity of a constructed wetland treating alkaline leachate after 5.5 years in operation.

Constructed wetlands (CWs) have been demonstrated as a cost-effective alternative to chemical treatment systems for mine waters, with the microbial communities attributed to promoting carbonation and aiding pH neutralization. However, few data are available for the long-term use of CWs treating alkaline leachates nor the activity of microbes within them. To investigate the feasibility of CW to buffer alkaline pH, a pilot-scale wetland was implemented in 2015 to treat alkaline bauxite residue leachate. After 5.5 years, samples of supernatant water and sediment were taken at 0.5 m increments along the 11 m long wetland. Waters were analysed for pH, EC and metal(loid) content, while sediment was subjected to physico-chemical assessment and element fractionation. Microbial biomass and community were assessed by phospholipid fatty acid analysis (PLFA) and functionality by the Rapid Automated Bacterial Impedance Technique (RABIT). Evidence presented demonstrates that the CW operating for 66 months effectively treats bauxite residue leachate, with reduced influent pH from 11.5 to 7.8. Trace element analysis revealed effective reduction in Al (94.9 %), As (86.7 %) and V (57.6 %) with substrate analysis revealing a frontloading of elevated pH and trace element content in the first 5 m of the wetland. Sediment Al, As and V were present mostly (>94 % of total) in recalcitrant forms. Sediment Na was mostly soluble (48-62 %), but soils were not sodic (ESP < 15 %). Investigations into the microbial community revealed greatest biomass was in the first 5 m of the wetland, where pH, EC and metal contents were greatest. Microbial respiration using endemic Phragmites australis as a substrate demonstrates an ability to cycle recalcitrant carbon sources within a CW system. These novel microbial findings highlight the need for further investigation into the microbial communities in alkaline CWs.

Synergy of phosphate recovery from sludge-incinerated ash and coagulant production by desalinated brine.

Wet-chemical approach is widely applied for phosphate recovery from incinerated ash of waste activated sludge (WAS), along with metals removed/recovered. The high contents of both aluminum (Al) and iron (Fe) in WAS-incinerated ash should be suitable for producing coagulants with some waste anions like Cl- and SO42- With acid (HCl) leaching and metals' removing, approximately 88 wt% of phosphorus (P) in the ash could be recovered as hydroxylapatite (HAP: Ca5(PO4)3OH); Fe3+ in the acidic leachate could be selectively removed/recovered by extraction with an organic solvent of tributyl phosphate (TBP), and thus a FeCl3-based coagulant could be synthesized by stripping the raffinate with the original brine (containing abundant Cl- and SO42-). Furthermore, a liquid poly-aluminum chloride (PAC)-based coagulant could also be synthesized with Al3+ removed from the ash and the brine, which behaved almost the same in the coagulation performance as a commercial coagulant on both phosphate and turbidity removals. Both P-recovery from the ash and coagulant production associated with the brine would enlarge the markets of both 'blue' phosphate and 'green' coagulants.

Copper recovery through biohydrometallurgy route: chemical and physical characterization of magnetic (m), non-magnetic (nm) and mix samples from obsolete smartphones.

The more modern electronics are, the smaller and complex printed circuit boards are. Thus, these materials are continually changed (physicochemically), increasing the copper concentrations in smartphones. In this sense, it is challenging to set standardized recycling processes to improve metal recovery. In addition, biohydrometallurgy is a clean and cheap process to obtain critical metals from low-grade sources and waste electronic equipment. Therefore, the aim of this work was to characterize, physicochemically, 21 PCBs from smartphones manufactured from 2010 to 2015, and then to recover the copper by Acidithiobacillus ferrooxidans (biohydrometallurgy). The PCBs were comminuted and separated into Magnetic (M), Nonmagnetic (NM) and without magnetic separation (MIX) samples. It was identified 217.8; 560.3 and 401.3 mg Cu/g of PCBs for M, NM and MIX samples, respectively. Regarding biohydrometallurgy, the culture media iron-supplemented (NM + Fe and MIX + Fe) increased the copper content by 2.6 and 7.2%, respectively, and the magnetic separation step was insignificant.

Recent advances of the core-shell MOFs in tumour therapy.

Coordination chemistry has always been vital to explore the material prominence of metal-organic systems. The metal-organic chemistry plays a fundamental role in decisive structural features, which are accountable for tuning the properties of materials. Tumour therapy has become an important research field of medical treatment in the world. Metal-organic frameworks (MOFs) have attracted extensive interest in medical science research due to their large effective surface area, clear pore network, and critical catalytic performance. Compared with traditional MOF materials, MOF materials with core-shell structures have a higher loading rate and better stability, which can overcome a single function. They have been successfully used in tumour medical research and have excellent prospects for diagnosing and treating various tumours. The current review article thoroughly describes the various synthetic approaches for engineering core-shell MOF materials, the structural types, and the potential functional applications. We also discussed core-shell MOF materials for the various treatment of tumours, such as tumour chemotherapy, tumour phototherapy and tumour microenvironment anti-hypoxia therapy. In this paper, the synthesized procedures of core-shell MOFs and their applications for tumour treatment have been discussed, and their future research has prospected. The current improved strategies, challenges, and prospects are also presented because of the metal-organic chemistry governing the structural modification of core-shell MOFs for tumour therapy applications. Therefore, the present review article opens a new door for medicinal chemists to tune the structural features of the core-shell MOF materials to modulate tumour therapy with simple, low-cost materials for better human lives.

Development of a novel chelation-based recycling strategy for the efficient decontamination of hazardous petroleum refinery spent catalysts.

The conventional hydrometallurgical methods for recycling refinery spent hydroprocessing catalysts are ineffective in simultaneously removing all metals (Ni, V, and Mo) in a single-stage operation. In this study, a novel octadentate chelating agent, diethylenetriaminepentaacetic acid (DTPA-C14H23N3O10), has been proposed for the first time to remove toxic metals (Ni, V, and Mo) in a single stage of operation from an industrial spent atmospheric residue desulfurization (ARDS) catalysts. It was discovered that the efficient formation of metal-DTPA complexes was attained under the optimum experimental conditions (60 °C, stirring - 150 rpm, S/L ration (w/v) of 2.5%, 7.5% DTPA, and medium pH-9) that resulted in the high removal of Mo (83.6%), V (81.3%) and Ni (64.1%) from the spent ARDS catalyst. Kinetic studies suggest that the leaching process followed a semi-empirical Avrami equation (R2 > 0.92), which predicted that the diffusion control reaction controlled the leaching. Species distribution and ecological risk analysis of the remaining metals in the insoluble residue (mostly Al2O3) indicated that the potential bioavailability of the remaining metals (except Ni) was significantly decreased, and residue poses a low ecological and contamination risk (individual contamination factor <1). Furthermore, the textural properties of the residue (BET surface area-103 m2/g and pore volume- 0.49 ml/g) were dramatically improved, suggesting that fresh hydroprocessing catalyst support can be synthesized using the leached residue. Compared to the conventional processes, the proposed chelating process is highly selective, closed-loop, and achieved high metal recovery in a single-stage operation while decreasing the environmental risks of the hazardous spent catalysts.

The quintessence of metallomics: a harbinger of a different life science based on the periodic table of the bioelements.

This year marks the 20th anniversary of the field of metallomics. As a landmark in time, it is an occasion to reflect on the past, present, and future of this integrated field of biometal sciences. A fundamental bias is one reason for having metallomics as a scientific discipline. The focus of biochemistry on the six non-metal chemical elements, collectively known with the acronym SPONCH (sulphur, phosphorus, oxygen, nitrogen, carbon, hydrogen), glosses over the fact that the lower quantities of many other elements have qualities that made them instrumental in the evolution of life and pivotal in numerous life processes. The metallome, alongside the genome, proteome, lipidome, and glycome, should be regarded as a fifth pillar of elemental-vis-à-vis molecular-building blocks in biochemistry. Metallomics as 'global approaches to metals in the biosciences' considers the biological significance of most chemical elements in the periodic table, not only the ones essential for life, but also the non-essential ones that are present in living matter-some at higher concentrations than the essential ones. The non-essential elements are bioactive with either positive or negative effects. Integrating the significance of many more chemical elements into the life sciences requires a transformation in learning and teaching with a focus on elemental biology in addition to molecular biology. It should include the dynamic interactions between the biosphere and the geosphere and how the human footprint is changing the ecology globally and exposing us to many additional chemical elements that become new bioelements.

Copper-mediated ß-amyloid toxicity and its chelation therapy in Alzheimer's disease.

The link between bio-metals, Alzheimer's disease (AD), and its associated protein, amyloid-ß (Aß), is very complex and one of the most studied aspects currently. Alzheimer's disease, a progressive neurodegenerative disease, is proposed to occurs due to the misfolding and aggregation of Aß. Dyshomeostasis of metal ions and their interaction with Aß has largely been implicated in AD. Copper plays a crucial role in amyloid-ß toxicity, and AD development potentially occurs through direct interaction with the copper-binding motif of APP and different amino acid residues of Aß. Previous reports suggest that high levels of copper accumulation in the AD brain result in modulation of toxic Aß peptide levels, implicating the role of copper in the pathophysiology of AD. In this review, we explore the possible mode of copper ion interaction with Aß, which accelerates the kinetics of fibril formation and promote amyloid-ß mediated cell toxicity in Alzheimer's disease and the potential use of various copper chelators in the prevention of copper-mediated Aß toxicity. KEYWORDS: Short Twitter Statement: Authors explore copper ion interaction w/ Aß and kinetics of fibril formation in promoting amyloid-ß mediated cell toxicity in Alzheimer's disease and the potential use of copper chelators in the prevention of copper-mediated Aß toxicity. SHORT TWITTER STATEMENT: Authors explore copper ion interaction w/Aß and kinetics of fibril formation in promoting amyloid-ß mediated cell toxicity in Alzheimer's disease and the potential use of copper chelators in the prevention of copper-mediated Aß toxicity.

Current and emerging mass spectrometry methods for the preclinical development of metal-based drugs: a critical appraisal.

This Trends article highlights the multiple ways in which the state-of-the-art molecular mass spectrometry can support the preclinical development of novel metal-based anticancer drugs. Examples from the recent literature-beyond routine characterization applications-are presented to illustrate what analytical and experimental design challenges are to be addressed to facilitate the translation of promising drug candidates to clinical practice.

Development of accurate temperature regulation culture system with metallic culture vessel demonstrates different thermal cytotoxicity in cancer and normal cells.

Hyperthermia has been studied as a noninvasive cancer treatment. Cancer cells show stronger thermal cytotoxicity than normal cells, which is exploited in hyperthermia. However, the absence of methods evaluating the thermal cytotoxicity in cells prevents the development of hyperthermia. To investigate the thermal cytotoxicity, culture temperature should be regulated. We, thus, developed a culture system regulating culture temperature immediately and accurately by employing metallic culture vessels. Michigan Cancer Foundation-7 cells and normal human dermal fibroblasts were used for models of cancer and normal cells. The findings showed cancer cells showed stronger thermal cytotoxicity than normal cells, which is quantitatively different from previous reports. This difference might be due to regulated culture temperature. The thermal stimulus condition (43 °C/30 min) was, further, focused for assays. The mRNA expression involving apoptosis changed dramatically in cancer cells, indicating the strong apoptotic trend. In contrast, the mRNA expression of heat shock protein (HSP) of normal cells upon the thermal stimulus was stronger than cancer cells. Furthermore, exclusively in normal cells, HSP localization to nucleus was confirmed. These movement of HSP confer thermotolerance to cells, which is consistent with the different thermal cytotoxicity between cancer and normal cells. In summary, our developed system can be used to develop hyperthermia treatment.

All-Optical and Label-Free Stimulation of Action Potentials in Neurons and Cardiomyocytes by Plasmonic Porous Metamaterials.

Optical stimulation technologies are gaining great consideration in cardiology, neuroscience studies, and drug discovery pathways by providing control over cell activity with high spatio-temporal resolution. However, this high precision requires manipulation of biological processes at genetic level concealing its development from broad scale application. Therefore, translating these technologies into tools for medical or pharmacological applications remains a challenge. Here, an all-optical nongenetic method for the modulation of electrogenic cells is introduced. It is demonstrated that plasmonic metamaterials can be used to elicit action potentials by converting near infrared laser pulses into stimulatory currents. The suggested approach allows for the stimulation of cardiomyocytes and neurons directly on commercial complementary metal-oxide semiconductor microelectrode arrays coupled with ultrafast pulsed laser, providing both stimulation and network-level recordings on the same device.

Plant Uptake of Lactate-Bound Metals: A Sustainable Alternative to Metal Chlorides.

Global agricultural intensification has prompted investigations into biostimulants to enhance plant nutrition and soil ecosystem processes. Metal lactates are an understudied class of organic micronutrient supplement that provide both a labile carbon source and mineral nutrition for plant and microbial growth. To gain a fundamental understanding of plant responses to metal lactates, we employed a series of sterile culture-vessel experiments to compare the uptake and toxicity of five metals (Zn, Mn, Cu, Ni, and Co) supplied in lactate and chloride salt form. Additionally, primary root growth in plate-grown Arabidopsis thaliana seedlings was used to determine optimal concentrations of each metal lactate. Our results suggest that uptake and utilization of metals in wheat (Triticum aestivum L.) when supplied in lactate form is comparable to that of metal chlorides. Metal lactates also have promotional growth effects on A. thaliana seedlings with optimal concentrations identified for Zn (0.5-1.0 µM), Mn (0.5-1.0 µM), Cu (0.5 µM), Ni (1.0 µM), and Co (0.5 µM) lactate. These findings present foundational evidence to support the use of metal lactates as potential crop biostimulants due to their ability to both supply nutrients and stimulate plant growth.

Role of metal complexation on the solubility and enzymatic hydrolysis of phytate.

Phytate is a dominant form of organic phosphorus (P) in the environment. Complexation and precipitation with polyvalent metal ions can stabilize phytate, thereby significantly hinder the hydrolysis by enzymes. Here, we studied the stability and hydrolyzability of environmentally relevant metal phytate complexes (Na, Ca, Mg, Cu, Zn, Al, Fe, Al/Fe, Mn, and Cd) under different pHs, presence of metal chelators, and thermal conditions. Our results show that the order of solubility of metal phytate complexes is as follows: i) for metal species: Na, Ca, Mg > Cu, Zn, Mn, Cd > Al, Fe, ii) under different pHs: pH 5.0 > pH 7.5), and iii) in the presence of chelators: EDTA> citric acid. Phytate-metal complexes are mostly resistant towards acid hydrolysis (except Al-phytate), and dry complexes are generally stable at high pressure and temperature under autoclave conditions (except Ca phytate). Inhibition of metal complex towards enzymatic hydrolysis by Aspergillus niger phytase was variable but found to be highest in Fe phytate complex. Strong chelating agents such as EDTA are insufficient for releasing metals from the complexes unless the reduction of metals (such as Fe) occurs first. The insights gained from this research are expected to contribute to the current understanding of the fate of phytate in the presence of various metals that are commonly present in agricultural soils.

The Story of 5d Metallocorroles: From Metal-Ligand Misfits to New Building Blocks for Cancer Phototherapeutics.

Porphyrin chemistry is Shakespearean: over a century of study has not withered the field's apparently infinite variety. Heme proteins continually astonish us with novel molecular mechanisms, while new porphyrin analogues bowl us over with unprecedented optical, electronic, and metal-binding properties. Within the latter domain, corroles occupy a special place, exhibiting a unique and rich coordination chemistry. The 5d metallocorroles are arguably the icing on that cake.New Zealand chemist Penny Brothers has used the word "misfit" to describe the interactions of boron, a small atom with a predilection for tetrahedral coordination, and porphyrins, classic square-planar ligands. Steve Jobs lionized misfits as those who see things differently and push humanity forward. Both perspectives have inspired us. The 5d metallocorroles are misfits in that they encapsulate a large 5d transition metal ion within the tight cavity of a contracted porphyrin ligand.Given the steric mismatch inherent in their structures, the syntheses of some 5d metallocorroles are understandably capricious, proceeding under highly specific conditions and affording poor yields. Three broad approaches may be distinguished.(a) In the metal-alkyl approach, a free-base corrole is exposed to an alkyllithium and the resulting lithio-corrole is treated with an early transition metal chloride; a variant of the method eschews alkyllithium and deploys a transition metal-alkyl instead, resulting in elimination of the alkyl group as an alkane and insertion of the metal into the corrole. This approach is useful for inserting transition metals from groups 4, 5, and, to some extent, 6, as well as lanthanides and actinides.(b) In our laboratory, we have often deployed a low-valent organometallic approach for the middle transition elements (groups 6, 7, 8, and 9). The reagents are low-valent metal-carbonyl or -olefin complexes, which lose one or more carbon ligands at high temperature, affording coordinatively unsaturated, sticky metal fragments that are trapped by the corrole nitrogens.(c) Finally, a metal acetate approach provides the method of choice for gold and platinum insertion (groups 10 and 11).This Account provides a first-hand perspective of the three approaches, focusing on the last two, which were largely developed in our laboratory. In general, the products were characterized with X-ray crystallography, electrochemistry, and a variety of spectroscopic methods. The physicochemical data, supplemented by relativistic DFT calculations, have provided fascinating insights into periodic trends and relativistic effects.An unexpected feature of many 5d metallocorroles, given their misfit character, is their remarkable stability under thermal, chemical, and photochemical stimulation. Many of them also exhibit long triplet lifetimes on the order of 100 µs and effectively sensitize singlet oxygen formation. Many exhibit phosphorescence in the near-infrared under ambient conditions. Furthermore, water-soluble ReO and Au corroles exhibit impressive photocytotoxicity against multiple cancer cell lines, promising potential applications as cancer phototherapeutics. We thus envision a bright future for the compounds as rugged building blocks for new generations of therapeutic and diagnostic (theranostic) agents.