Pathway complexity in π-conjugated materials

To arrive at functional organic materials with optimal molecular organization, control over the aggregation process is a prerequisite. Often however, multiple pathways are involved that compete for the same molecular building block, a phenomenon known as pathway complexity. As a result, the material–made from small molecules or polymers–can get entrapped in a metastable pathway while a more stable, but slower formed morphology is aimed for. Vice versa, the equilibrium state can be obtained easily but another, less stable morphology is desired as it has more interesting properties. In both cases, the solution processing, starting from molecularly dissolved material, should be optimized to select the desired aggregation pathway. This perspective aims to outline the importance of mechanistic insights derived from self-assembly of 1D fibers in diluted solutions to unravel and control aggregation pathways involved in the processing of p-conjugated materials

Benzene-1,3,5-tricarboxamide : a versatile ordering moiety for supramolecular chemistry

After their first synthesis in 1915 by Curtius, benzene-1,3,5-tricarboxamides (BTAs) have become increasingly important in a wide range of scientific disciplines. Their simple structure and wide accessibility in combination with a detailed understanding of their supramolecular self-assembly behaviour allow full utilization of this versatile, supramolecular building block in applications ranging from nanotechnology to polymer processing and biomedical applications. While the opportunities in the former cases are connected to the self-assembly of BTAs into one-dimensional, nanometer-sized rod like structures stabilised by threefold H-bonding, their multivalent nature drives applications in the biomedical field. This review summarises the different types of BTAs that appeared in the recent literature and the applications they have been evaluated in. Currently, the first commercial applications of BTAs are emerging. The adaptable nature of this multipurpose building block promises a bright future

Programmable supramolecular polymerizations

\u3cp\u3eLiving large: Rational design of self-assembly pathways has been demonstrated in supramolecular polymers. By controlling the concentration of an aggregation-competent monomer through intramolecular interactions, living supramolecular polymerization conditions were achieved. This universal approach can be used to obtain aggregates of well-defined length and narrow dispersity, and allows access to new supramolecular polymer architectures.\u3c/p\u3

Alternation and tunable composition in hydrogen bonded supramolecular copolymers

Sequence control in supramolecular copolymers is limited by the selectivity of the associating monomer end groups. Here we introduce the use of monomers with aminopyrimidinone and aminohydroxynaphthyridine quadruple hydrogen bonding end groups, which both homodimerize, but form even stronger heterodimers. These features allow the formation of supramolecular copolymers with a tunable composition and a preference for alternating sequences

Model-driven engineering of supramolecular buffering by multivalency

A supramolecular system in which the concentration of a molecule is buffered over several orders of magnitude is presented. Molecular buffering is achieved as a result of competition in a ring–chain equilibrium of multivalent ureidopyrimidinone monomers and a monovalent naphthyridine molecule which acts as an end-capper. While we previously only considered divalent ureidopyrimidinone monomers we now present a model-driven engineering approach to improve molecular buffering using multivalent ring–chain systems. Our theoretical models reveal an odd–even effect where even-valent molecules show superior buffering capabilities. Furthermore, we predict that supramolecular buffering can be significantly improved using a tetravalent instead of a divalent molecule, since the tetravalent molecule can form two intramolecular rings with different “stabilities” due to statistical effects. Our model predictions are validated against experimental 1H NMR data, demonstrating that model-driven engineering has considerable potential in supramolecular chemistry. \u3cbr/\u3

DNA-based nanodevices controlled by purely entropic linker domains

\u3cp\u3eWe demonstrate here the rational design of purely entropic domains as a versatile approach to achieve control of the input/output response of synthetic molecular receptors. To do so and to highlight the versatility and generality of this approach, we have rationally re-engineered two model DNA-based receptors: a clamp-like DNA-based switch that recognizes a specific DNA sequence and an ATP-binding aptamer. We show that, by varying the length of the linker domain that connects the two recognition portions of these receptors, it is possible to finely control their affinity for their specific ligand. Through mathematical modeling and thermodynamic characterization, we also demonstrate for both systems that entropy changes associated with changes in linker length are responsible for affinity modulation and that the linker we have designed behaves as a disordered random-coil polymer. The approach also allows us to regulate the ligand concentration range at which the receptors respond and show optimal specificity. Given these attributes, the use of purely entropic domains appears as a versatile and general approach to finely control the activity of synthetic receptors in a highly predictable and controlled fashion.\u3c/p\u3

An equilibrium model for chiral amplification in supramolecular polymers

We describe a model that rationalizes amplification of chirality in cooperative supramolecular copolymerization. The model extends nucleation-elongation based equilibrium models for growth of supramolecular homopolymers to the case of two monomer and aggregate types. Using the principle of mass-balance for the two monomer types, we derive a set of two nonlinear equations, describing the thermodynamic equilibrium state of the system. These equations can be solved by numerical methods, but also analytical approximations are derived. The equilibrium model allows two-sided growth of the aggregates and can be applied to symmetric supramolecular copolymerizations, corresponding to the situation in which the monomers are enantiomerically related, as well as to the more general case of nonsymmetric supramolecular copolymerizations. In detail, so-called majority-rules phenomena in supramolecular systems with isodesmic as well as cooperative growth are analyzed. Comparison of model predictions with experimental data shows that the model gives a very good description of both titration and melting curves. When the system shows cooperative growth, the model leads to a phase diagram in which the presence of the various aggregate types is given as a function of composition and temperature

Protein scaffolds and higher-order complexes in synthetic biology

Interactions between proteins control molecular functions such as signalling or metabolic activity. Assembly of proteins via scaffold proteins or in higher-order complexes is a key regulatory mechanism. Understanding and functionally applying this concept requires the construction, study, and utilization of synthetic scaffolds. This chapter first describes protein scaffolding in the context of its natural function as well as the underlying mechanistic origins via mathematical models and simulations. This is then funnelled into examples of synthetic biology approaches to engineer new scaffolds and their usage as regulators of signalling networks and metabolic engineering