Combining local conformational preferences and solvophobic effects in helical aromatic oligoamide foldamers.

Aromatic oligoamide foldamers were designed using a newly-developed monomer so that helical folding was promoted by both local conformation preferences and solvophobic effects. Solid phase synthesis provided quick access to the desired sequences. Sharp solvent-driven conformational transitions that depended on sequence length were evidenced by both NMR and UV absorption spectroscopies.

Large-Amplitude Conformational Changes in Self-Assembled Multi-Stranded Aromatic Sheets.

The orchestration of ever larger conformational changes is made possible by the development of increasingly complex foldamers. Aromatic sheets, a rare motif in synthetic foldamer structures, have been designed so as to form discrete stacks of intercalated aromatic strands through the self-assembly of two identical subunits. Ion-mobility ESI-MS confirms the formation of compact dimers.

Aromatic β-sheet foldamers based on tertiary squaramides.

The preference of N,N-aryl, alkyl tertiary amides for cis conformations has been exploited through the use of tertiary squaramides as hairpin turn units that promote the folding of aromatic β-sheets. Head-to-head aromatic arrangements were shown to prevail in sufficiently long bent aromatic sequences.

Unraveling the Multistimuli Responses of a Complex Dynamic System of Pseudopeptidic Macrocycles.

Dynamic combinatorial libraries (DCLs) are excellent benchmark models to study the stimuli-responsiveness of chemical networks. However, increasingly complex systems are difficult to analyze with simple data analysis methods, because many variables and connections must be considered for their full understanding. Here we propose the use of multivariate data analysis methods to bisect the evolution of a complex synthetic dynamic library of pseudopeptidic macrocycles, containing side chains with charges of different sign.

Entropy-driven homochiral self-sorting of a dynamic library.

A dynamic mixture of stereoisomeric macrocycles derived from glutamic acid displayed a homochiral self-selection when increasing the acetonitrile content of the aqueous mixed medium. The homochiral self-sorting required the anionic form of the side chains and increased at higher temperature, implying an entropic origin. Conformational analysis (NMR and MD simulations) allowed us to explain the observed behaviour.

Pseudopeptidic compounds for the generation of dynamic combinatorial libraries of chemically diverse macrocycles in aqueous media.

A straightforward four-step synthesis leads to the preparation of C-symmetric dithiols containing a central aromatic core and amino acid side chains. These building blocks allow the preparation of dynamic covalent libraries of pseudopeptidic macrocycles in aqueous media that cover a broad range of polarities, functional groups and bulkiness mirroring the diversity found in natural peptides. The versatility of the generated dynamic libraries has been illustrated by the amplification of two different members from the same library upon the action of two biologically relevant templates.

Adaptive Correction from Virtually Complex Dynamic Libraries: The Role of Noncovalent Interactions in Structural Selection and Folding.

The hierarchical self-assembling of complex molecular systems is dictated by the chemical and structural information stored in their components. This information can be expressed through an adaptive process that determines the structurally fittest assembly under given environmental conditions. We have set up complex disulfide-based dynamic covalent libraries of chemically and topologically diverse pseudopeptidic compounds.

Salt-induced adaptation of a dynamic combinatorial library of pseudopeptidic macrocycles: unraveling the electrostatic effects in mixed aqueous media.

Dynamic combinatorial libraries are powerful systems for studying adaptive behaviors and relationships, as models of more complex molecular networks. With this aim, we set up a chemically diverse dynamic library of pseudopeptidic macrocycles containing amino-acid side chains with differently charged residues (negative, positive, and neutral). The responsive ability of this complex library upon the increase of the ionic strength has been thoroughly studied.

Constitutional self-selection from dynamic combinatorial libraries in aqueous solution through supramolecular interactions.

We describe the predominant formation of a specific constitution arising from the combination of building blocks with different topologies through disulphide chemistry in a Dynamic Combinatorial Library (DCL). The supramolecular interactions established by a zwitterionic cysteine moiety are responsible for the self-selection of one product from all the virtual members of a large library.

The emergence of halophilic evolutionary patterns from a dynamic combinatorial library of macrocyclic pseudopeptides.

The increase of the ionic strength amplifies the species bearing acidic side chains from a bio-inspired dynamic combinatorial library of macrocyclic pseudopeptides, in close resemblance to the evolution observed for the proteins of halophilic microorganisms.