Grafting of the 2,8-dithia-5-aza-2,6-pyridinophane macrocycle on SBA-15 mesoporous silica for the removal of Cu2+ and Cd2+ ions from aqueous solutions: synthesis, adsorption, and complex stability studies

Silica-based mesoporous materials have received growing attention in metal recovery from industrial processes, although, in general, the adsorption of metal ions by silanols is rather poor. Nevertheless, a great improvement of metal ion removal from aqueous solutions can be achieved by grafting metal-chelators on the particles’ surface. Combining the metal-chelating properties of organic ligands with the high surface area of mesoporous silica particles makes these hybrid nanostructured materials a new horizon in metal recovery, sensing and controlled storage of metal ions in industrial and mining processes. Here, the 2,8-dithia-5-aza-2,6-pyridinophane (L) macrocycle was grafted on SBA-15 mesoporous silica to obtain the SBA-L mesoporous adsorbent for the removal and controlled recovery of Cd2+ and Cu2+ ions from aqueous solution in a broad pH range (4-11). By grafting about 0.3 mmol g−1 of L on SBA-15 a maximum loading capacity of 20.9 mg g−1 and 31.8 mg g−1 was obtained for Cu2+ and Cd2+, respectively. The adsorption kinetics can be described with the pseudo-second order model, while the adsorption isotherm (298 K) followed the Langmuir model. The latter, together with potentiometric studies, suggests that the adsorption mechanism is based on metal chelation by the grafted macrocycle. In summary, SBA-L is an effective copper(ii) and cadmium(ii) chelator for possible applications where metal removal, storage and recovery are of basic importance

Towards the functional high-resolution coordination chemistry of blood plasma human serum albumin

Human serum albumin (HSA)is a monomeric, globular, multi-carrier and the most abundant protein in the blood. HSA displays multiple ligand binding sites with extraordinary binding capacity for a wide range of ions and molecules. For decades, HSA's ability to bind to various ligands has led many scientists to study its physiological properties and protein structure; indeed, a better understanding of HSA-ligand interactions in human blood, at the atomic level, will likely foster the development of more potent, and overall more performant, diagnostic and therapeutic tools against serious human disorders such as diabetes, cardiovascular disorders, and cancer. Here, we present a concise overview of the current knowledge of HSA's structural characteristics, and its coordination chemistry with transition metal ions, within the scope and limitations of current techniques and biophysical methods to reach atomic resolution in solution and in blood serum. We also highlight the overwhelming need of a detailed atomistic understanding of HSA dynamic structures and interactions that are transient, weak, multi-site and multi-step, and allosterically affected by each other. Considering the fact that HSA is a current clinical tool for drug delivery systems and a potential contender as molecular cargo and nano-vehicle used in biophysical, clinical and industrial fields, we underline the emerging need for novel approaches to target the dynamic functional coordination chemistry of the human blood serum albumin in solution, at the atomic level

Synthesis and Mass Spectrometry Analysis of Mimosine-Containing Peptides

AbstractNon-proteinogenic amino acids are widely explored group of compounds due to their chemical properties and great potential of application in the combinatorial chemistry, medicinal investigation etc. Therefore the synthetic methods of their incorporation to the peptide chain are required. l-Mimosine, (S)-α-amino-β-(3-hydoxy-4-oxo-1,4-dihydropyridin-1-yl)-propanoic acid), is a plant amino acid, known to induce apoptosis in human pancreatic cancer xenografts. Here we present our investigations on the synthesis of mimosine-containing peptide and their ESI-MS/MS analysis. We successfully applied Fmoc-protected mimosine a with a free hydroxy ketone group for efficient peptide synthesis in the presence of HATU as a coupling reagent without the formation of side products. Additionally the tandem mass spectrometry analysis revealed the characteristic loss of the heterocyclic ring from mimosine residue side chain. The described method allows insertion of mimosine residue at any endo-position within a peptide sequence. The obtained results may be useful in the synthesis and mass spectrometry analysis of various mimosine-containing peptides

Metal complex formation and anticancer activity of cu(I) and cu(ii) complexes with metformin

Metformin has been used for decades in millions of type 2 diabetes mellitus patients. In this time, correlations between metformin use and the occurrence of other disorders have been noted, as well as unpredictable metformin side effects. Diabetes is a significant cancer risk factor, but unexpectedly, metformin-treated diabetic patients have lower cancer incidence. Here, we show that metformin forms stable complexes with copper (II) ions. Both copper(I)/metformin and copper(II)/metformin complexes form adducts with glutathione, the main intracellular antioxidative peptide, found at high levels in cancer cells. Metformin reduces cell number and viability in SW1222 and K562 cells, as well as in K562-200 multidrug-resistant cells. Notably, the antiproliferative effect of metformin is enhanced in the presence of copper ions

What doesn't kill you makes you stronger: Future applications of amyloid aggregates in biomedicine

Amyloid proteins are linked to the pathogenesis of several diseases including Alzheimer’s disease, but at the same time a range of functional amyloids are physiologically important in humans. Although the disease pathogenies have been associated with protein aggregation, the mechanisms and factors that lead to protein aggregation are not completely understood. Paradoxically, unique characteristics of amyloids provide new opportunities for engineering innovative materials with biomedical applications. In this review, we discuss not only outstanding advances in biomedical applications of amyloid peptides, but also the mechanism of amyloid aggregation, factors aecting the process, and core sequences driving the aggregation. We aim with this review to provide a useful manual for those who engineer amyloids for innovative medicine solutions

The Best Peptidomimetic Strategies to Undercover Antibacterial Peptides

Health-care systems that develop rapidly and efficiently may increase the lifespan of humans. Nevertheless, the older population is more fragile, and is at an increased risk of disease development. A concurrently growing number of surgeries and transplantations have caused antibiotics to be used much more frequently, and for much longer periods of time, which in turn increases microbial resistance. In 1945, Fleming warned against the abuse of antibiotics in his Nobel lecture: “The time may come when penicillin can be bought by anyone in the shops. Then there is the danger that the ignorant man may easily underdose himself and by exposing his microbes to non-lethal quantities of the drug make them resistant”. After 70 years, we are witnessing the fulfilment of Fleming’s prophecy, as more than 700,000 people die each year due to drug-resistant diseases. Naturally occurring antimicrobial peptides protect all living matter against bacteria, and now different peptidomimetic strategies to engineer innovative antibiotics are being developed to defend humans against bacterial infections

You are what you eat: Application of Metabolomics Approaches to Advance Nutrition Research

A healthy condition is defined by complex human metabolic pathways that only function properly when fully satisfied by nutritional inputs. Poor nutritional intakes are associated with a number of metabolic diseases, such as diabetes, obesity, atherosclerosis, hypertension, and osteoporosis. In recent years, nutrition science has undergone an extraordinary transformation driven by the development of innovative software and analytical platforms. However, the complexity and variety of the chemical components present in different food types, and the diversity of interactions in the biochemical networks and biological systems, makes nutrition research a complicated field. Metabolomics science is an “-omic”, joining proteomics, transcriptomics, and genomics in affording a global understanding of biological systems. In this review, we present the main metabolomics approaches, and highlight the applications and the potential for metabolomics approaches in advancing nutritional food research

NMR as a “gold standard” method in drug design and discovery

Studying disease models at the molecular level is vital for drug development in order to improve treatment and prevent a wide range of human pathologies. Microbial infections are still a major challenge because pathogens rapidly and continually evolve developing drug resistance. Cancer cells also change genetically, and current therapeutic techniques may be (or may become) ineffective in many cases. The pathology of many neurological diseases remains an enigma, and the exact etiology and underlying mechanisms are still largely unknown. Viral infections spread and develop much more quickly than does the corresponding research needed to prevent and combat these infections; the present and most relevant outbreak of SARS-CoV-2, which originated in Wuhan, China, illustrates the critical and immediate need to improve drug design and development techniques. Modern day drug discovery is a time-consuming, expensive process. Each new drug takes in excess of 10 years to develop and costs on average more than a billion US dollars. This demonstrates the need of a complete redesign or novel strategies. Nuclear Magnetic Resonance (NMR) has played a critical role in drug discovery ever since its introduction several decades ago. In just three decades, NMR has become a “gold standard” platform technology in medical and pharmacology studies. In this review, we present the major applications of NMR spectroscopy in medical drug discovery and development. The basic concepts, theories, and applications of the most commonly used NMR techniques are presented. We also summarize the advantages and limitations of the primary NMR methods in drug development

Cholinium-Based Ionic Liquids from Hydroxycinnamic Acids as New Promising Bioactive Agents: A Combined Experimental and Theoretical Investigation

Cholinium-based ionic liquids (Cho-ILs) are very attractive compounds for medicinal and pharmaceutical applications as bioavailability enhancers in drug formulations and active components in pharmaceutical ingredients. In this study, we synthesized six Cho-ILs from hydroxycinnamic acids (HCA) ([Cho][HCA] ILs), a group of bioactive compounds with poor water solubility. [Cho][HCA] ILs and their parent acids were evaluated for solubility, thermal stability, and antioxidant activity. Furthermore, [Cho][HCA] ILs were screened for their cytotoxicity. To rationalize the experimental antioxidant activities, density functional theory (DFT) calculations were performed. The theoretical approach allowed for identification of the most likely radical scavenging mechanisms involving HCAs and the corresponding ionic forms under the studied experimental conditions and to rationalize the observed activity differences between salts and acids. Overall, our results revealed a higher solubility and free-radical scavenging activity for [Cho][HCA] ILs than corresponding HCAs, a relatively high thermal stability (melting temperature > 100 °C) and negligible cytotoxicity activity. Furthermore, DFT calculations showed that both the hydrogen atom transfer and the sequential proton loss electron transfer mechanisms are likely to occur in aqueous and ethanolic solutions. The picture emerging from our results supports the increasingly expressed idea that [Cho][HCA]ILs are promising candidates for applications in pharmaceutical formulatio