The controlled assembly of nanoparticles in thin film form on solid supports, both as monolayers and as superlattice structures, is a problem of considerable topical interest. Among the many interactions used to program the assembly of nanoparticles, electrostatic forces are particularly interesting for many reasons. This Account deals with assembling surface-modified nanoparticles in thin film form using electrostatic interactions at the air-water interface and in thermally evaporated lipid films. The generality of the electrostatic assembly protocol is demonstrated in the immobilization of DNA and proteins in lipid films.

An isothermal titration calorimetric (ITC) investigation of the interaction of DNA bases and PNA base monomers with gold nanoparticles is described revealing a binding sequence in the order C > G > A > T. Direct measurement of the strength of interaction of ligands with nanogold by ITC has important implications in surface modification strategies for biomedical, catalysis, and nanoarchitecture applications.

The organization of nanoparticles into superstructures of predefined geometry is an important challenge in the area of nanoscale architecture. Attractive Coulombic interaction between positively charged amine groups on gold particle surfaces and negatively charged phosphate backbones of DNA molecules (see Figure) drives the self‐assembly of gold nanoparticles into linear supercluster structures.

Isothermal titration calorimetry (ITC) is a powerful and highly sensitive technique commonly used to study interactions between biomolecules in dilute aqueous solutions, both from thermodynamic and kinetics points of view. In this report, we show that ITC may be used to follow the binding of ligands such as amino acids to the surface of inorganic materials such as gold nanoparticles. More specifically, we have studied the binding of one basic amino acid, lysine, and an acidic amino acid, aspartic acid, with aqueous gold nanoparticles at physiological pH. Strong binding of aspartic acid with the gold nanoparticles under these conditions is indicated by ITC, while weak binding was observed in the case of lysine. The differences in binding are attributed to protonation of amine groups in lysine at physiological pH (pI ∼ 9.4) while they are not protonated for aspartic acid (pI ∼ 2.77). That this is the likely mechanism is indicated by the ITC measurement of binding of lysine with nanogold at pH 11 (when the amine groups are not protonated). The binding of the amino acids with gold nanoparticles has been validated with other techniques such as gel electrophoresis and X-ray photoemission spectroscopy.

Since its discovery 12 years ago, aminoethylglycyl peptide nucleic acid (aeg-PNA) has emerged as one of the successful DNA mimics for potential therapeutic and diagnostic applications. An important requisite for in vivo applications that has received inadequate attention is engineering PNA analogues for able discrimination between DNA and RNA as binding targets. Our approach toward this aim is based on structural preorganization of the backbone to hybridization-competent conformations to impart binding selectivity. This strategy has allowed us to design locked PNAs to achieve specific hybridization with DNA or RNA with aims to increase the binding strength without losing the binding specificity. This Account presents results of our rationale in design of different conformationally constrained PNA analogues, their synthesis, and evaluation of hybridization specificities.