Alaa S. Abd-El-Aziz

Sandwich complex-containing macromolecules: property tunability through versatile synthesis.

Sandwich complexes feature unique properties as the physical and electronic properties of a hydrocarbon ligand or its derivative are integrated into the physical, electronic, magnetic, and optical properties of a metal. Incorporation of these complexes into macromolecules results in intriguing physical, electrical, and optical properties that were hitherto unknown in organic-based macromolecules. These properties are tunable through well-designed synthetic strategies. This review surveys many of the synthetic approaches that have resulted in tuning the properties of sandwich complex-containing macromolecules. While the past two decades have seen an ever-growing number of research publications in this field, gaps remain to be filled. Thus, we expect this review to stimulate research interest towards bridging these gaps, which include the insolubility of some of these macromolecules as well as expanding the scope of the sandwich complexes.

Co-Administration of Resveratrol and Lipoic Acid, or Their Synthetic Combination, Enhances Neuroprotection in a Rat Model of Ischemia/Reperfusion

The present study demonstrates the benefits of combinatorial antioxidant therapy in the treatment of ischemic stroke. Male Sprague-Dawley rats were anaesthetised and the middle cerebral artery (MCA) was occluded for 30 minutes followed by 5.5 hours of reperfusion. Pretreatment with resveratrol 30 minutes prior to MCA occlusion resulted in a significant, dose-dependent decrease in infarct volume (p<0.05) compared to vehicle-treated animals. Neuroprotection was also observed when resveratrol (2×10−3 mg/kg; iv) was administered within 60 minutes following the return of blood flow (reperfusion). Pretreatment with non-neuroprotective doses of resveratrol (2×10−6 mg/kg) and lipoic acid (LA; 0.005 mg/kg) in combination produced significant neuroprotection as well. This neuroprotection was also observed when resveratrol and LA were administered 15 minutes following the onset of MCA occlusion. Subsequently, we synthetically combined resveratrol and LA in both a 1∶3 (UPEI-200) and 1∶1 (UPEI-201) ratio, and screened these new chemical entities in both permanent and transient ischemia models. UPEI-200 was ineffective, while UPEI-201 demonstrated significant, dose-dependent neuroprotection. These results demonstrate that combining subthreshold doses of resveratrol and LA prior to ischemia-reperfusion can provide significant neuroprotection likely resulting from concurrent effects on multiple pathways. The additional protection observed in the novel compound UPEI 201 may present opportunities for addressing ischemia-induced damage in patients presenting with transient ischemic episodes.

Antimicrobial resistance challenged with metal-based antimicrobial macromolecules.

Antimicrobial resistance threatens the achievements of science and medicine, as it deactivates conventional antimicrobial therapeutics. Scientists respond to the threat by developing new antimicrobial platforms to prevent and treat infections from these resistant strains. Metal-based antimicrobial macromolecules are emerging as an alternative to conventional platforms because they combine multiple mechanisms of action into one platform due to the distinctive properties of metals. For example, metals interact with intracellular proteins and enzymes, and catalyse various intracellular processes. The macromolecular architecture offers a means to enhance antimicrobial activity since several antimicrobial moieties can be conjugated to the scaffold. Further, these macromolecules can be fabricated into antimicrobial materials for contact-killing medical implants, fabrics, and devices. As volatilization or leaching out of the antimicrobial moieties from the macromolecular scaffold is reduced, these medical implants, fabrics, and devices can retain their antimicrobial activity over an extended period. Recent advances demonstrate the potential of metal-based antimicrobial macromolecules as effective platforms that prevent and treat infections from resistant strains. In this review these advances are thoroughly discussed within the context of examples of metal-based antimicrobial macromolecules, their mechanisms of action and biocompatibility.

Photoinduced Synthesis of Dual‐Emissive Tetraphenylethene‐Based Dendrimers with Tunable Aggregates and Solution States Emissions

Photoactive materials are actively researched, piloting breakthroughs that have enriched fundamental understanding of science, and have led to real applications. Tetraphenylethene, a photoactive molecule that is of interest from fundamental and applied perspectives, features photochemical properties that are not exploited in the design of photoactive, dual-emissive materials. Here, tetraphenylethene-based, dual-emissive dendrimers are constructed via a synthetic approach that involves a photochemical reaction that exploits the photochemistry of tetraphenylethene. These dendrimers are emissive in solution and in the aggregate state with tunable dual emissions at 368 and 469 nm. The photochemical reaction also tunes the size of the aggregates, increasing the size after UV irradiation. The reported synthetic strategy is a direct and facile approach to accessing dual-emissive macromolecules, especially tetraphenylethene-based systems for real applications.

Aggregation enhanced excimer emission (AEEE) with efficient blue emission based on pyrene dendrimers

Fluorescence dendrimers have been developed, which exhibit aggregation enhanced excimer emission (AEEE). In this article, the synthesis and characterization of three generations of organoiron dendrimers with a flexible core is described. Different photoactive pyrene moieties with and without alkyl chains were used to functionalize the dendritic peripheries. The luminescence properties of these dendrimers were examined in various solvents and concentrations as well as in THF/water mixtures. It was determined that the alkyl chain attached to pyrene moieties had a significant impact on the emission wavelength. Interestingly, dendrimers exhibited weak emission when dissolved in organic solvents but strong emission when aggregated in mixed organic/aqueous solvents. Different emission behaviour was observed in the case of second generation dendrimers, due to the presence of a high number of pyrene moieties. The solution emitted much bluer light relative to the zero and first generations, which emitted around 480 nm. In addition, the change in the distance between two pyrene moieties affects the formation of strong or weak excimers. The excimer–monomer intensity ratios (IE/IM) showed the existence of the unique phenomenon of AEEE. The large difference between the aggregated molecules in various THF/water ratios was detected by TEM. Redox activities of the dendrimers were also measured. A single redox wave was displayed in all dendrimers and the intensity of the redox waves increased by increasing the dendrimer generation. All dendrimers possessed good thermal stability and were shown to have two thermal degradation processes.

UPEI-300, a conjugate of lipoic acid and edaravone, mediates neuroprotection in ischemia/reperfusion.

Edaravone, an electron spin trapper with radical scavenging activity, has been shown to be effective in reducing infarct volume in humans following ischemic stroke. However, concerns of edaravone-induced renal toxicity have limited its clinical adoption. Previous work has demonstrated that edaravone produced significant neuroprotection when injected prior to a period of ischemia and/or reperfusion. The current investigation was designed to determine if a newly synthesized co-drug consisting of lipoic acid and edaravone, named UPEI-300, could produce neuroprotection in in vitro and/or an in vivo rodent model of stroke. UPEI-300 produced dose-dependent neuroprotection in vitro and was subsequently tested in vivo. Male rats were anaesthetized and the middle cerebral artery was occluded for 30 min followed by 5.5 h of reperfusion (ischemia/reperfusion; I/R). Pre-administration of UPEI-300 dose-dependently decreased infarct volume. Significant neuroprotection was also observed when UPEI-300 (1.0 mg/kg) was injected during the 30 min period of ischemia as well as up to 60 min following the start of reperfusion. These results indicate that a co-drug consisting of edaravone and lipoic acid is a potent neuroprotectant, and clinically, the use of such a novel co-drug following an ischemic stroke might maintain neuroprotection while potentially decreasing edaravone associated renal toxicity.

Redox-active cationic organoiron complex: a promising lead structure for developing antimicrobial agents with activity against Gram-positive pathogens including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium

We report a new class of antimicrobial agent, a redox-active, cationic organometallic, η6-arene–η5-cyclopentadienyliron(II) complex, with activity against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium. Structure–property relationship investigations revealed that the antimicrobial activity against these pathogens, especially methicillin-resistant Staphylococcus aureus, is tunable. The ability of this new class of antimicrobial agent to induce cellular oxidative stress was confirmed using dichlorodihydrofluorescein assay. We attributed the induction of oxidative stress as a mechanism that contributes to the overall antimicrobial activity of these compounds. Generally, this antimicrobial agent was non-toxic to BJ fibroblast cell lines at ≤128 μg mL−1. The η6-arene–η5-cyclopentadienyliron(II) complex represents a potential lead structure for the development of topical antimicrobial therapeutics to combat resistant strains of Gram-positive bacteria.

CHAPTER 4:Functional Materials Based on Metal-Containing Polymers

Since the dawn of human civilization, there has been a demand for materials that include ceramics, metals, and polymers. Increasing demand as well as the need for enhanced performance has driven material scientists to research metal-containing polymers as complements of these materials. Consequently, metal-containing polymers that integrate the excellent thermal, electronic, optical, and magnetic properties of metals with the lightweight, low cost, and in some cases, the chemical stability of organic-based polymers have been designed, and used as catalysts, sensors, ceramic precursors, magnetic materials, and electrical conductors. This chapter provides an overview of some of these functional metal-containing polymers.

Increasing the Biological Stability Profile of a New Chemical Entity, UPEI-104, and Potential Use as a Neuroprotectant Against Reperfusion-Injury.

Previous work in our laboratory demonstrated the utility of synthetic combinations of two naturally occurring, biologically active compounds. In particular, we combined two known anti-oxidant compounds, lipoic acid and apocynin, covalently linked via an ester bond (named UPEI-100). In an animal model of ischemia-reperfusion injury (tMCAO), UPEI-100 was shown to produce equivalent neuroprotection compared to each parent compound, but at a 100-fold lower dose. However, it was determined that UPEI-100 was undetectable in any tissue samples almost immediately following intravenous injection. Therefore, the present investigation was done to determine if biological stability of UPEI-100 could be improved by replacing the ester bond with a more bio cleavage-resistant bond, an ether bond (named UPEI-104). We then compared the stability of UPEI-104 to the original parent compound UPEI-100 in human plasma as well as liver microsomes. Our results demonstrated that both UPEI-100 and UPEI-104 could be detected in human plasma for over 120 min; however, only UPEI-104 was detectable for an average of 7 min following incubation with human liver microsomes. This increased stability did not affect the biological activity of UPEI-104 as measured using our tMCAO model. Our results suggest that combining compounds using an ether bond can improve stability while maintaining biological activity.

A Nonisothermal Study of Organoiron Poly(alkynyl methacrylate) Coordinated to Dicobalt Hexacarbonyl Using Advanced Kinetics Modelling

Non-isothermal crystallisation studies of Organoiron poly(alkynyl methacrylate)s coordinated to dicobalt hexacarbonyl using differential scanning calorimetry (DSC) are reported. Two exothermic peaks appear on crystallisation of the polymers under investigation. Four isoconversional methods (the differential method of Friedman, the integral methods of Ozawa–Flynn–Wall and Vyazovkin and ASTM E698) were used to determine the variation of the activation energy for crystallisation with reaction progress. The DSC data were analysed with the advanced thermokinetics software package AKTS-Thermokinetics. The change of a methyl group, CH3, to a hydrogen atom, H, in the system tends to shift the crystallisation peaks to a lower temperature at the same heating rate. However, the methyl group has lower activation energy. Prediction of the isothermal reaction progress was employed to calculate the reaction model, g(α), and the system was found to follow the A1.5 solid state reaction model. The Raman spectra and X-ray diffraction of the polymer were also investigated.