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.

Formyl benzeno boronic acids rapidly and selectively react with N-terminal cysteines to yield a reversible boronated thiazolidine that may be used in the interactive orthogonal modification of peptides.

The antioxidant activity of the phenolic compounds present in industrial black liquors obtained from the two cooking processes (kraft and sulphite) used in Portugal to produce Eucalyptus globulus pulp was evaluated. The black liquors treated at several pH values were extracted with ethyl acetate. Phenolic fractions were further separated by liquid chromatography of the crude extracts of kraft liquor at pH = 6 and sulphite liquor at the original pH. Total phenolic content was determined in terms of gallic acid equivalents (Folin-Ciocalteu colorimetric method), and the antioxidant activity in the crude extracts at several pH values and in the separated fractions was measured using the DPPH test for radical scavenging capacity. The total phenolic content of crude extracts and separated fractions ranged from 92.7 to 181.6 and from 91.6 to 1,099.6 mg GAE/g, respectively, while the antioxidant activity index (AAI) ranged from 2.20 to 3.41 and from 2.21 to 11.47 respectively, showing very strong antioxidant activity in all studied cases. The fractions separated by column chromatography were submitted to mass spectrometry analysis and the results were compared to others in the literature of natural products, mainly from Eucalyptus, and the characteristic bands of functional groups were identified by 1H-NMR and FTIR. These methods allowed the identification of 17 phenolic compounds.

The first highly enantioselective intermolecular (4 + 2) cycloaddition between allenes and dienes is reported. The reaction provides good yields of optically active cyclohexenes featuring diverse substitution patterns and up to three stereocenters. Key to the success of the process is the use of newly designed axially chiral N-heterocyclic carbene− gold catalysts.