Synthesis and characterization of terpene-derived cationic bolaamphiphiles
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Cited by 2 publications
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The use of cationic and ionizable cationic lipids in pharmaceutical products, however, is a double-edged sword, as these excipients are of considerable safety concerns. Because of their permanent or pHdependent cationic nature, they perturbate cellular and nuclear membranes, trigger the release of degrading enzymes from lysosomes, cause mitochondrial permeabilization and dysfunction, generate reactive oxygen species (ROS), alter cytoplasmatic enzyme functions, and damage DNA. [3] To address this substantial shortcoming of cationic and ionizable cationic lipids, biodegradable alternatives have been introduced that are rapidly degraded in vivo to preferably endogenous metabolites. The design of such lipids is inspired by natural cationic or ionizable cationic compounds like arginine, lysine or betaine that are generally regarded as safe. Their conjugation to endogenous lipids like fatty acids or cholesterol results in amphiphilic lipids. As ester and amide bonds are cleaved in vivo by numerous enzymes such as lipases, esterases, and proteases, they are the preferred linkages between these natural building blocks.Since the FDA approved ethyl Nα-lauroyl-l-arginate as biodegradable food preservative being effective against a broad range of Gram-positive and Gram-negative bacteria, yeasts, and molds in 2005, [4] the potential use of biodegradable cationic and ionizable cationic lipids as pharmaceutical excipients has been evaluated by numerous research groups. As these excipients exhibit the same properties as their non-biodegradable counterparts but causing relatively low adverse effects, they will likely substitute currently used non-biodegradable lipids in the future. Within this review, we provide an overview on the different types of biodegradable cationic and ionizable cationic lipids, their synthesis and cleavage by endogenous enzymes. Applications in drug delivery systems and as antimicrobial agents are discussed. A guideline on their design and application is provided and an outlook on future developments is given. Building Blocks and Formation of Cationic and Ionizable Cationic LipidsGenerally, biodegradable cationic and ionizable cationic lipids are composed of biocompatible building blocks that are conjugated via a linkage such as an ester or amide bond. [5] Representative building blocks and linkages are depicted in Figure 1. Endogenous enzymes can break these linkages and degrade Cationic and ionizable cationic lipids are broadly applied as auxiliary agents, but their use is associated with adverse effects. If these excipients are rapidly degraded to endogenously occurring metabolites such as amino acids and fatty acids, their toxic potential can be minimized. So far, synthesized and evaluated biodegradable cationic and ionizable cationic lipids already showed promising results in terms of functionality and safety. Within this review, an overview about the different types of such biodegradable lipids, the available building blocks, their synthesis and cleavage by endogenous enzymes is provided. Moreover, ...
The use of cationic and ionizable cationic lipids in pharmaceutical products, however, is a double-edged sword, as these excipients are of considerable safety concerns. Because of their permanent or pHdependent cationic nature, they perturbate cellular and nuclear membranes, trigger the release of degrading enzymes from lysosomes, cause mitochondrial permeabilization and dysfunction, generate reactive oxygen species (ROS), alter cytoplasmatic enzyme functions, and damage DNA. [3] To address this substantial shortcoming of cationic and ionizable cationic lipids, biodegradable alternatives have been introduced that are rapidly degraded in vivo to preferably endogenous metabolites. The design of such lipids is inspired by natural cationic or ionizable cationic compounds like arginine, lysine or betaine that are generally regarded as safe. Their conjugation to endogenous lipids like fatty acids or cholesterol results in amphiphilic lipids. As ester and amide bonds are cleaved in vivo by numerous enzymes such as lipases, esterases, and proteases, they are the preferred linkages between these natural building blocks.Since the FDA approved ethyl Nα-lauroyl-l-arginate as biodegradable food preservative being effective against a broad range of Gram-positive and Gram-negative bacteria, yeasts, and molds in 2005, [4] the potential use of biodegradable cationic and ionizable cationic lipids as pharmaceutical excipients has been evaluated by numerous research groups. As these excipients exhibit the same properties as their non-biodegradable counterparts but causing relatively low adverse effects, they will likely substitute currently used non-biodegradable lipids in the future. Within this review, we provide an overview on the different types of biodegradable cationic and ionizable cationic lipids, their synthesis and cleavage by endogenous enzymes. Applications in drug delivery systems and as antimicrobial agents are discussed. A guideline on their design and application is provided and an outlook on future developments is given. Building Blocks and Formation of Cationic and Ionizable Cationic LipidsGenerally, biodegradable cationic and ionizable cationic lipids are composed of biocompatible building blocks that are conjugated via a linkage such as an ester or amide bond. [5] Representative building blocks and linkages are depicted in Figure 1. Endogenous enzymes can break these linkages and degrade Cationic and ionizable cationic lipids are broadly applied as auxiliary agents, but their use is associated with adverse effects. If these excipients are rapidly degraded to endogenously occurring metabolites such as amino acids and fatty acids, their toxic potential can be minimized. So far, synthesized and evaluated biodegradable cationic and ionizable cationic lipids already showed promising results in terms of functionality and safety. Within this review, an overview about the different types of such biodegradable lipids, the available building blocks, their synthesis and cleavage by endogenous enzymes is provided. Moreover, ...
C–H Activation via Group 8–10 Pincer Complexes: A Mechanistic Approach
C–H bond activation is a crucial synthetic strategy widely utilized in both academic and industrial settings. Due to the strong and kinetically inert nature of the C–H bond, its functionalization typically requires metal-based catalysts. This review highlights the most significant advancements in homogeneously catalyzed reactions using pincer complexes with metals from groups 8–10, capable of promoting challenging C–H activation, published since 2010. In particular, it focuses on C–H bond activation for borylation, isomerization, and dehydrogenation, among other processes, discussing their scope and mechanistic insights.
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