Principal Investigator Allan Myerson
Self-assembled monolayers (SAMs) are ordered molecular assemblies that are formed spontaneously by the adsorption of a surfactant with a specific affinity of its headgroup to a substrate . A SAM molecule consists of a headgroup, chain or backbone and endgroup. A SAM system is typically defined by the headgroup-substrate pair such as thiol SAMs on gold substrates and silane-based SAMs on SiO2.
Polymorphism Studies -- Crystals of a chemical compound can exist in more than one structure, which is known as polymorphism. Polymorph screening, in which discovering and characterizing all possible solid forms that a target compound can have, is required in the early stage of the drug development process. Using patterned SAM’s arrays of small solution droplets on the nano- and pico liter scale are generated. By inducing supersaturation withing the droplet (through evaporation, cooling or vapor diffusion) nucleation occurs and crystals are formed within each droplet. The solid state form of each crystal produced is characterized using Raman and optical microscopy. A large number of experiments are possible in a short time (1000-3000) so that statistical information of the relative rates of nucleation of each potential polymorphic form can be obtained.
Nano-crystal Formation -- The formation of organic molecular crystals with sizes below 500 nm is of great interest to the pharmaceutical industry since an enhanced solubility and dissolution rate can potentially increase drug bioavailability.
Methods to produce nanosized organic molecular crystals include both ‘top down’ and ‘bottom up’ approaches. Top down methods,such as milling and high pressure homogenization, employ crystalor particle breakage and can impact the stability and crystallinity of the solid. Bottom up methods, such as supercritical fluidcrystallization and impinging jet crystallization, exploit high levels of supersaturation and can lead to the formation of amorphous materials and/or oils or an undesired crystalline form (polymorph). These issues have generated interest in methods for producing nanosized organic molecular crystals at low supersaturations. Recent work has focused on methods that confine the crystallization volume, such as emulsions and nanoporous materials. Using photolithography on silicon wafers, we have produced patterned SAM’s with as small as 500 nm. Using these SAM’s we have demonstrated the ability to produce glycine crystals as small as 100 nm . The solubility of crystals obtained was measured as a function of crystal size and employed along with the Ostwald-Freundlich equation to predict solubility enhancement vs crystal size.