Isothermal titration calorimetry (ITC) allows the determination of DeltaG degrees, DeltaH degrees, and DeltaS degrees from a single experiment and is thus widely used for studying binding thermodynamics in both biological and synthetic supramolecular systems. However, it is widely believed that it is not possible to derive accurate thermodynamic information from ITC experiments in which the Wiseman "c" parameter (which is the product of the receptor concentration and the binding constant, K(a)) is less than ca. 10, constraining its use to high affinity systems. Herein, experimental titrations and simulated data are used to demonstrate that this dogma is false, especially for low affinity systems, assuming that (1) a sufficient portion of the binding isotherm is used for analysis, (2) the binding stoichiometry is known, (3) the concentrations of both ligand and receptor are known with accuracy, and (4) there is an adequate level of signal-to-noise in the data. This study supports the validity of ITC for determining the value of K(a) and, hence, DeltaG degrees from experiments conducted under low c conditions but advocates greater caution in the interpretation of values for DeltaH degrees. Therefore, isothermal titration calorimetry is a valid and useful technique for studying biologically and synthetically important low affinity systems.

Multivalency plays a major role in biological processes and particularly in the relationship between pathogenic microorganisms and their host that involves protein-glycan recognition. These interactions occur during the first steps of infection, for specific recognition between host and bacteria, but also at different stages of the immune response. The search for high-affinity ligands for studying such interactions involves the combination of carbohydrate head groups with different scaffolds and linkers generating multivalent glycocompounds with controlled spatial and topology parameters. By interfering with pathogen adhesion, such glycocompounds including glycopolymers, glycoclusters, glycodendrimers and glyconanoparticles have the potential to improve or replace antibiotic treatments that are now subverted by resistance. Multivalent glycoconjugates have also been used for stimulating the innate and adaptive immune systems, for example with carbohydrate-based vaccines. Bacteria present on their surfaces natural multivalent glycoconjugates such as lipopolysaccharides and S-layers that can also be exploited or targeted in anti-infectious strategies.

Multivalent interactions, which rely upon noncovalent bonds, are essential ingredients in the mediation of biological processes, as well as in the construction of complex (super)structures for materials applications. A fundamental understanding of multivalency in supramolecular chemistry is necessary not only to construct motors and devices on the nanoscale but also to synthesize model systems to provide insight into how biological processes work. This Account focuses on the application of multivalency to supramolecular chemistry in particular and the nanosciences in general.