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The molecular recognition of Tyr-containing peptide copolymers with pseudopeptidic cages has been studied using a combination of fluorescence and NMR spectroscopies. Fluorescence titrations rendered a reasonable estimation of the affinities, despite the presence of dynamic quenching masking the unambiguous detection of the supramolecular complexes. Regarding NMR, the effect of polypeptide (PP) binding on relaxation and diffusion parameters of the cages is much more reliable than the corresponding chemical shift perturbations. To that, purification of the commercial PPs is mandatory to obtain biopolymers with lower polydispersity. Thus, the relaxation/diffusion-filtered 1 H spectra of the cages in the absence vs presence of the PPs represent a suitable setup for the fast detection of the noncovalent interactions. Additional key intermolecular NOE cross-peaks supported by molecular models allow the proposal of a structure of the supramolecular species, stabilized by the Tyr encapsulation within the cage cavity and additional attractive polar interactions between the side chains of cage and PP, thus defining a binding epitope with a potential for implementing sequence selectivity. Accordingly, the cages bearing positive/negative residues prefer to bind the peptides having complementary negative/positive side chains close to the target Tyr, suggesting an electrostatic contribution to the interaction. Overall, our results show that both techniques represent a powerful and complementary combination for studying cage-to-PP molecular recognition processes.

A degenerate zinc-templated catalytic system containing two bipyridine ligands with redundant functional groups for either enamine or hydrogen bond formation was applied to the asymmetric aldol reaction. This concept led to both a higher probability of reaction and rate acceleration. Thus, the catalyst loading could be decreased to a remarkable 2 mol % in what we think is a general approach.

Artificial receptors able to recognise biologically relevant molecules or ions have gained interest in the chemical community because they offer a plethora of posibilities. Molecular cage compounds are polycyclic compounds with a cavity designed for the encapsulation of guest species. Once inside the host cavity, the substrate can be transported through membranes and protected from the action of enzymes or other reactive species, thus offering the possibility of interfering with biological systems. Commonly, enzymes have been an inspiration for chemists in the search and design of defined cavities for different purposes. However, the chemical preparation of molecular cages has struggled with many synthetic challenges but this effort is worthwhile as they are a very promising tool for many applications ranging from sensing, delivery, purification or even promotion of/prevention from chemical modifications. Since the early reports at the end of the 60s, this field has experienced a growing interest; this review summarises the progress in the preparation and study of cage-like compounds highlighting their importance in biological applications.

Acidic microenvironments in solid tumors are a hallmark of cancer. Inspired by that, we designed a family of pseudopeptidic cage-like anionophores displaying pH-dependent activity. When protonated, they efficiently bind chloride anions. They also transport chloride through lipid bilayers, with their anionophoric properties improving at acidic pH, suggesting an H + /Cl - symport mechanism. NMR studies in DPC micelles demonstrate that the cages bind chloride within the lipid phase. The chloride affinity and the chloride-exchange rate with the aqueous bulk solution are improved when the pH is lowered. This increases cytotoxicity towards lung adenocarcinoma cells at the pH of the microenvironment of a solid tumor. These properties depend on the nature of the amino-acid side chains of the cages, which modulate their lipophilicity and interactions with the cell membrane. This paves the way towards using pH as a parameter to control the selectivity of cytotoxic ionophores as anticancer drugs., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The study of molecular networks represents a conceptual revolution in chemistry. Building on previous knowledge and after understanding the rules of non-covalent interactions, the design of stimulus-responsive chemical systems is possible. Herein we report a new strategy, based on the reorganization of a dynamic chemical network that generates new fluorescent associations in the presence of cysteine or cystine. The binding and sensing units are encoded in the components that dynamically assemble and disassemble responding to external stimuli as a successful tool to detect both cysteine and cystine in aqueous media. Moreover, the dynamic sensing system works in human urine, as a prospective application for cystinuria diagnosis., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)