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Ionic detergents enable applications and cause harm in biospheres due to cell toxicity. The utility of covalent combinations between ionic and non‐ionic detergent headgroups in modulating cell toxicity remains speculative due to the yet rarely explored synthesis. We close this gap and establish the modular synthesis of ionic/non‐ionic hybrid detergents. We restructure a combinatorial methallyl dichloride one‐pot coupling into a two‐step coupling, which reduces by‐products, improves product yields, and enables the gram‐scale preparation of asymmetric, cationic/non‐ionic and anionic/non‐ionic hybrid detergents. Our modular synthesis delivers new modalities for the design of ionic detergents, including an unprecedented scaling of properties that determine applications, such as charge, critical micelle concentration, solubilizing properties, hard water tolerance, and cell compatibility. We uncover that shielding the charge in ionic headgroups can switch the detergent species that is toxic to cells from monomers to mixtures of monomers and micellar assemblies. Establishing the chemistry of ionic/non‐ionic hybrid detergents provides a missing evolutionary link in the structural comparison of ionic and non‐ionic detergents, enables an easy synthesis access to yet unexplored chemical spaces of asymmetric hybrid materials, and delivers new modalities for designing the toxicity of supramolecular nanomaterials. [ABSTRACT FROM AUTHOR]

Detergents are amphiphilic molecules that serve as enabling steps for today's world applications. The increasing diversity of the detergentome is key to applications enabled by detergent science. Regardless of the application, the optimal design of detergents is determined empirically, which leads to failed preparations, and raising costs. To facilitate project planning, here we review synthesis strategies that drive the diversification of the detergentome. Synthesis strategies relevant for industrial and academic applications include linear, modular, combinatorial, bio‐based, and metric‐assisted detergent synthesis. Scopes and limitations of individual synthesis strategies in context with industrial product development and academic research are discussed. Furthermore, when designing detergents, the selection of molecular building blocks, i. e. head, linker, tail, is as important as the employed synthesis strategy. To facilitate the design of safe‐to‐use and tailor‐made detergents, we provide an overview of established head, linker, and tail groups and highlight selected scopes and limitations for applications. It becomes apparent that most recent contributions to the increasing chemical diversity of detergent building blocks originate from the development of detergents for membrane protein studies. The overview of synthesis strategies and molecular blocks will bring us closer to the ability to predictably design and synthesize optimal detergents for challenging future applications. [ABSTRACT FROM AUTHOR]

The article titled "Cover Feature: Trends in the Diversification of the Detergentome" in the journal ChemPlusChem explores the chemical diversity of detergents and their applications. The authors, Virginia Wycisk, Marc-Christian Wagner, and Leonhard H. Urner, provide a description of the detergentome, which refers to the entirety of all detergents. This description aims to assist with project planning and the synthesis of detergents for future applications. The cover design for the article was created by Leonhard H. Urner. [Extracted from the article]

Herein, we present a new synthetic route to cyanine-based heterobifunctional dyes and their application as fluorescent linkers between polymers and biomolecules. The synthesized compounds, designed in the visible spectral range, are equipped with two different reactive groups for highly selective conjugation under physiological conditions. By applying indolenine precursors with functionalized benzenes, we achieved water-soluble asymmetric cyanine dyes bearing maleimido and N-hydroxysuccinimidyl functionalities in a three-step synthesis. Spectroscopic characterization revealed good molar absorption coefficients and moderate fluorescence quantum yields. Further reaction with polyethylene glycol yielded dye-polymer conjugates that were subsequently coupled to the antibody cetuximab, often applied in cancer therapy. Successful coupling was confirmed by mass shifts detected by gel electrophoresis. Receptor-binding studies and live-cell imaging revealed that labeling did not alter the biological function. In sum, we provided a successful synthetic pathway to rigid heterobifunctional cyanine dyes that are applicable as fluorescent linkers, for example, for connecting antibodies with macromolecules. Our approach contributes to the field of bioconjugation chemistry, such as antibody-drug conjugates by combining diagnostic and therapeutic approaches. [ABSTRACT FROM AUTHOR]

Detergent chemistry enables applications in the world today while harming safe operating spaces that humanity needs for survival. Aim of this review is to support a holistic thought process in the design of detergent chemistry. We harness the planetary boundary concept as a framework for literature survey to identify progresses and knowledge gaps in context with detergent chemistry and five planetary boundaries that are currently transgressed, i.e. climate, freshwater, land system, novel entities, biosphere integrity. Our survey unveils the status of three critical challenges to be addressed in the years to come, including (i) the implementation of a holistically, climate‐friendly detergent industry; (ii) the alignment of materialistic and social aspects in creating technical solutions by means of sustainable chemistry; (iii) the development of detergents that serve the purpose of applications but do not harm the biosphere in their role as novel entities. Specifically, medically relevant case reports revealed that even the most sophisticated detergent design cannot sufficiently accelerate drug discovery to outperform the antibiotic resistance development that detergents simultaneously promote as novel entities. Safe operating spaces that humanity needs for its survival may be secured by directing future efforts beyond sustainable chemistry, resource efficiency, and net zero emission targets. [ABSTRACT FROM AUTHOR]

This article provides a comprehensive analysis of the impact of detergent chemistry on exceeding planetary boundaries, specifically focusing on antimicrobial resistance, drug development, and the integrity of the biosphere. The authors emphasize the need for a holistic approach to the chemical design of detergents and identify progress and knowledge gaps related to detergent chemistry and five planetary boundaries that are currently being exceeded. The study highlights three critical challenges that need to be addressed, including the development of a climate-friendly detergent industry, aligning materialistic and social aspects in sustainable chemistry, and creating detergents that serve a purpose without harming the biosphere. The article also discusses the potential of sustainable chemistry in promoting adherence to planetary boundaries and highlights the impact of detergent chemistry on human health and the environment. It concludes by suggesting that further research is needed to understand the effects of detergent molecules and to develop detergents that minimize their impact on the biosphere. [Extracted from the article]

The syntheses of novel amphiphilic 5,5′,6,6′‐tetrachlorobenzimidacarbocyanine (TBC) dye derivatives with aminopropanediol head groups, which only differ in stereochemistry (chiral enantiomers, meso form and conformer), are reported. For the achiral meso form, a new synthetic route towards asymmetric cyanine dyes was established. All compounds form J aggregates in water, the optical properties of which were characterised by means of spectroscopic methods. The supramolecular structure of the aggregates is investigated by means of cryo‐transmission electron microscopy, cryo‐electron tomography and AFM, revealing extended sheet‐like aggregates for chiral enantiomers and nanotubes for the mesomer, respectively, whereas the conformer forms predominately needle‐like crystals. The experiments demonstrate that the aggregation behaviour of compounds can be controlled solely by head group stereochemistry, which in the case of enantiomers enables the formation of extended hydrogen‐bond chains by the hydroxyl functionalities. In case of the achiral meso form, however, such chains turned out to be sterically excluded. [ABSTRACT FROM AUTHOR]

Due to their unique structure and properties, water-soluble fullerene derivatives are of great interest for various biomedical purposes. In this work, solution behavior, encapsulation and release properties, biocompatibility, and cellular uptake pathways of fullerene-polyglycerol amphiphiles (FPAs) with defined structures are investigated. The number of polyglycerol branches attached to the surface of fullerene affects the physicochemical properties of FPAs dramatically but not their cellular uptake. Release of encapsulated hydrophobic dyes from FPAs strongly depends on the number of their branches. Conjugation of a pH-sensitive dye to the FPAs as a probe showed that their self-assemblies are taken up through endocytotic pathways. It was observed that FPAs are able to transfer small molecules into cells both above and below their critical aggregation concentration. Taking advantage of the water solubility, biocompatibility, and transfer-ability of FPAs, they might find use as unimolecular carriers for future biomedical applications. [ABSTRACT FROM AUTHOR]

G protein-coupled receptors can adopt many different conformational states, each of them exhibiting different restraints towards downstream signaling pathways. One promising strategy to identify and quantify this conformational landscape is to introduce a cysteine at a receptor site sensitive to different states and label this cysteine with a probe for detection. Here, the application of NMR of hyperpolarized 129Xe for the detection of the conformational states of human neuropeptide Y2 receptor is introduced. The xenon trapping cage molecule cryptophane-A attached to a cysteine in extracellular loop 2 of the receptor facilitates chemical exchange saturation transfer experiments without and in the presence of native ligand neuropeptide Y. High-quality spectra indicative of structural states of the receptor–cage conjugate were obtained. Specifically, five signals could be assigned to the conjugate in the apo form. After the addition of NPY, one additional signal and subtle modifications in the persisting signals could be detected. The correlation of the spectroscopic signals and structural states was achieved with molecular dynamics simulations, suggesting frequent contact between the xenon trapping cage and the receptor surface but a preferred interaction with the bound ligand. [ABSTRACT FROM AUTHOR]

In this work, we report a new, simple, gram-scale method for synthesizing water-soluble fullerene-polyglycerol amphiphiles (FPAs) that self-assemble into partially and fully crosslinked nanoclusters with the ability to controllably transport hydrophobic and hydrophilic agents. [ABSTRACT FROM AUTHOR]