Thin-layer studies on surface functionalization of polyetherimide: Hydrolysis versus amidation

Among the high-performance and engineering polymers, polyimides and the closely related polyetherimide (PEI) stand out by their capability to react with nucleophiles under relatively mild conditions. By targeting the phthalimide groups in the chain backbone, post-functionalization offers a pathway to adjust surface properties such as hydrophilicity, solvent resistance, and porosity. Here, we use ultrathin PEI films on a Langmuir trough as a model system to investigate the surface functionalization with ethylene diamine and tetrakis(4-aminophenyl)porphyrin as multivalent nucleophiles. By means of AFM, Raman spectroscopy, and interfacial rheology, we show that hydrolysis enhances the chemical and mechanical stability of ultrathin films and allows for the formation of EDC/NHS-activated esters. Direct amidation of PEI was achieved in the presence of a Lewis acid catalyst, resulting in free amine groups rather than cross-linking. When comparing amidation with hydrolysis, we find a greater influence of the latter on material properties. Graphic abstract

Investigation of Fluorine-18 Labelled Peptides for Binding to Cholecystokinin-2 Receptors with High Affinity

Many cancers of neuroendocrine origin overexpress cholecystokinin-2 receptors (CCK-2R) including medullary thyroid cancer, small cell lung cancer and other lung carcinoids. Fluorine-18 labelled peptides targeting CCK-2R enable direct visualization and quantification of this receptor in vivo using positron emission tomography imaging. CP04 1 and MG11 2 are two previously described truncated peptides derived from the native CCK-2R hormone ligand, gastrin. The N-terminus of the MG11 2 octopeptide was chemically modified with various fluorine containing aromatic (4-fluorobenzoate), heterocyclic (6-fluoronicotinate) and aliphatic (2-fluoropropionate) moieties. To assess the impact these modifications had on CCK-2R binding, ligand-binding assays were conducted using A431 cells overexpressing human CCK-2R. MG11 2 modified by 4-fluorobenzoate (FB-MG11 3) demonstrated the highest binding affinity (0.20 nM) followed by MG11 2 modified by 6-fluoronicotinate (FNic-MG11 4; 0.74 nM) and 2-fluoropropionate (FP-MG11 5; 1.80 nM), respectively. Whilst indirect labelling of MG11 2 using fluorine-18 labelled activated esters of fluorobenzoate and 6-fluoronicotinate was unsuccessful, direct fluorine-18 labelling at the N-terminus modified with 6-nitronicotinate afforded a 47.6% radiochemical yield of [18F]FNic-MG11. Unfortunately, [18F]FNic-MG11 4 was chemically unstable, decomposing slowly through defluorination, thereby impeding any further work with this radiotracer.

Membrane Transport Inspired Hydrolysis of Non-activated Esters at Near Physiological pH

A positively charged micelle, loaded with substrates was transported selectively to the reaction site (cathode) to promote the proximity and localization of the reactants (ester and hydroxide). The guided vehicular...

Polymer Endgroup Control Through a Trifunctional Cobalt-Mediated Radical Polymerization: New Avenues for Synthesising Protein Conjugates

Cobalt-mediated radical polymerisations (CMRPs) have been initiated by the radical decarboxylation of tetrachlorophthalimide activated esters. This allows for the controlled radical polymerisation of both activated and less activated monomers across a broad temperature range with a single cobalt species, with incorporation of polymer endgroups derived from simple carboxylic acids derivatives and termination with an organozinc reagent. This method has been applied to the synthesis of a water-soluble protein/polymer conjugate, demonstrating the first example of CMRP in protein conjugation.

Membrane Trafficking Inspired Hydrolysis of Non-Activated Esters at Physiological pH

Natural enzymes establish the proximity of the substrates to perform challenging reactions in aqueous medium, whereas most chemical catalysts typically follow stochastic way and are less efficient. Inspired by the membrane trafficking, a core biological process, herein we report that positively charged micro heterogeneous vehicles loaded with substrate could be trafficked suitably at the site of the reaction to promote the localization and proximity of the reactants. The guided vehicular delivery coupled with electrolysis overcomes the entropic barrier related to the proximity of the reactants and allows the hydrolysis of non-activated esters at physiological pH. Mechanistic investigations suggest that the reaction utilizes the electrochemical energy to generate hydroxide ion at the cathode and the positively charged micellar vehicles (loaded with substrates) trafficked selectively near cathode to promote the hydrolysis. The in situ modulation of surface charge was exploited to accelerate or inhibit the hydrolysis in a controlled manner akin to cofactors or zymogens of natural enzymes. We believe this elegant membrane trafficking inspired approach paves the way for the further applications of proximity controlled selective transformations in organic synthesis using green aqueous medium.<br>

Membrane Trafficking Inspired Hydrolysis of Non-Activated Esters at Physiological pH

Natural enzymes establish the proximity of the substrates to perform challenging reactions in aqueous medium, whereas most chemical catalysts typically follow stochastic way and are less efficient. Inspired by the membrane trafficking, a core biological process, herein we report that positively charged micro heterogeneous vehicles loaded with substrate could be trafficked suitably at the site of the reaction to promote the localization and proximity of the reactants. The guided vehicular delivery coupled with electrolysis overcomes the entropic barrier related to the proximity of the reactants and allows the hydrolysis of non-activated esters at physiological pH. Mechanistic investigations suggest that the reaction utilizes the electrochemical energy to generate hydroxide ion at the cathode and the positively charged micellar vehicles (loaded with substrates) trafficked selectively near cathode to promote the hydrolysis. The in situ modulation of surface charge was exploited to accelerate or inhibit the hydrolysis in a controlled manner akin to cofactors or zymogens of natural enzymes. We believe this elegant membrane trafficking inspired approach paves the way for the further applications of proximity controlled selective transformations in organic synthesis using green aqueous medium.<br>

4-Nitrophenyl activated esters are superior synthons for indirect radiofluorination of biomolecules

A comparative study of PNP- and TFP-activated esters of radiolabelled prosthetic groups demonstrates the superiority of PNP esters in terms of stability and yields for use in one-step radiolabelling of small molecules and peptides.

Graphene oxide: a convenient metal-free carbocatalyst for facilitating amidation of esters with amines

Herein, we have reported a graphene oxide (GO) catalyzed condensation of non-activated esters and amines, that can enable diverse amides to be synthesized from abundant ethyl esters forming only volatile alcohol as a by-product.

A practical ortho-acylation of aryl iodides enabled by moisture-insensitive activated esters via palladium/norbornene catalysis

Herein reported is a practical Catellani-type ortho-acylation of aryl iodides enabled by employing moisture-insensitive esters as the electrophile via C(O)–O bond cleavage.