Maleimide chemistry stands out in the bioconjugation toolbox by virtue of its synthetic accessibility, excellent reactivity, and practicability. The second-generation of clinically approved antibody-drug conjugates (ADC) and much of the current ADC pipeline in clinical trials contain the maleimide linkage. However, thiosuccinimide linkages are now known to be less robust than once thought, and ergo, are correlated with suboptimal pharmacodynamics, pharmacokinetics, and safety profiles in some ADC constructs. Rational design of novel generations of maleimides and maleimide-type reagents have been reported to address the shortcomings of classical maleimides, allowing for the formation of robust bioconjugate linkages. This review highlights the main strategies for rational reagent design that have allowed irreversible bioconjugations in cysteines, reversible labelling strategies and disulfide re-bridging.

The preparation of high value‐added chemicals from renewable resources is a crucial approach towards a sustainable economy. One prominent alternative to the production of petroleum‐based chemicals from fossil resources is through the sequential Diels‐Alder/aromatization reactions of biomass‐derived furan platforms. This Concept is focused on the recent boom in bio‐based furan DA strategies for aromatization of bio‐based platform chemicals, particularly that of furfurals, ranging from indirect use and activation strategies to recent examples of direct DA reaction of these electron‐withdrawing biomass‐derived furans.

Cyclopropenes have become an important mini-tag tool in chemical biology, participating in fast inverse electron demand Diels–Alder and photoclick reactions in biological settings.

Inverse-electron demand Diels–Alder cycloadditions have emerged as important bioorthogonal reactions in chemical biology. Understanding and predicting reaction rates for bioconjugation reactions is fundamental for evaluating their efficacy in biological systems. Here, we present multivariate models to predict the second order rate constants of bioorthogonal inverse-electron demand Diels–Alder reactions involving 1,2,4,5-tetrazines derivatives. A data-driven approach was used to model these reactions by parametrizing both the dienophiles and the dienes partners. The models are statistically robust and were used to predict/extrapolate the outcome of several reactions as well as to identify mechanistic differences among similar reactants.

A new chemoselective (enzymatic desymmetrization/Ru‐catalyzed C−H activation) sequence to obtain differently substituted furans from the largely available 2,5‐furandicarboxylic acid (FDCA) was developed. Series of di‐ and trisubstituted furans were prepared in very good yields and excellent chemoselectivity. This study discloses a new approach towards valorization of the furanics platform through the use of FDCA as a stable intermediate, thus circumventing the chemical instability of the parent 5‐hydroxymethylfurfural.

3A5AF, a biomass derived furan obtained from chitin, is used as a diene in the Diels–Alder reaction with maleimides. This allows the incorporation of bio-based nitrogen into the final products, a challenge unmet by commonly used furanics.

Cr 3+ modified readily available cation exchange resins were prepared and explored as heterogeneous bifunctional catalysts for the dehydration of glucose to 5-hydroxymethylfurfural (HMF) in tetraethyl ammonium bromide (TEAB)/water as reaction medium. Excellent HMF isolated yields of up to 70% were achieved using simple crystallization of the reaction medium (TEAB) from ethyl acetate/ethanol which allowed the isolation of HMF in high purity. The best identified catalyst (Amberlyst 15/Cr 3+ ) exhibited high activity over 4 cycles. The loss of activity was attributed to the decreased number of acidic sites of the catalyst, thus a simple treatment of the catalyst with 10% HCl efficiently restored its activity in the following cycles.

Cancer nanotherapy suffers from lowyield delivery that is imposed by tumour pathophysiological barriers. Top-down drug delivery strategies, including exosomes and cell membrane-coated particles, can improve safety and efficacy owing to the innate biointerfacial properties of these platforms. Here, we discuss the technological challenges that need to be overcome for their clinical implementation.