Crystal polymorphism in a carbamazepine derivative: Oxcarbazepine

Although crystal polymorphism of carbamazepine (CBZ), an anticonvulsant used to treat epilepsy, has been known for decades, the phenomenon has only recently been noted for its keto-derivative oxcarbazepine (OCB). Here it is demonstrated that OCB possesses at least three anhydrous polymorphs. Although all forms are morphologically similar, making differentiation between crystal modifications by optical microscopy difficult, powder X-ray diffraction, Raman spectroscopy, and thermomicroscopy show distinctive differences. These techniques provide an efficient method of distinguishing between the three polymorphs. The crystal structure of form II of OCB is reported for the first time and the structure of form I has been redetermined at low temperature. Remarkably, both the molecular conformation and crystal packing of form II are in excellent agreement with the blind prediction made in 2007. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:794–803, 2010Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/64542/1/21873_ftp.pd

Polymorphs and hydrates of acyclovir

Acyclovir (ACV) has been commonly used as an antiviral for decades. Although the crystal structure of the commercial form, a 3:2 ACV/water solvate, has been known since 1980s, investigation into the structure of anhydrous ACV has been limited. Here, we report the characterization of four anhydrous forms of ACV and a new hydrate in addition to the known hydrate. Two of the anhydrous forms appear as small needles and are stable to air exposure, whereas the third form is morphologically similar but quickly absorbs water from the atmosphere and converts back to the commercial form. The high-temperature modification is achieved by heating anhydrous form I above 180°C. The crystal structures of anhydrous form I and a novel hydrate are reported for the first time. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:949–963, 2011Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79417/1/22336_ftp.pd

Metastability in pressure-induced structural transformations of CdSe/ZnS core/shell nanocrystals

The kinetics and thermodynamics of structural transformations under pressure depend strongly on particle size due to the influence of surface free energy. By suitable design of surface structure, composition, and passivation it is possible, in principle, to prepare nanocrystals in structures inaccessible to bulk materials. However, few realizations of such extreme size-dependent behavior exist. Here we show with molecular dynamics computer simulation that in a model of CdSe/ZnS core/shell nanocrystals the core high pressure structure can be made metastable under ambient conditions by tuning the thickness of the shell. In nanocrystals with thick shells, we furthermore observe a wurtzite to NiAs transformation, which does not occur in the pure bulk materials. These phenomena are linked to a fundamental change in the atomistic transformation mechanism from heterogenous nucleation at the surface to homogenous nucleation in the crystal core. Our results suggest a new route towards expanding the range of available nanoscale materials

High Pressure Behavior of Nanomaterials

The investigation of the properties of matter under high pressure is becoming increasing important to many scientific fields, including chemistry, physics, and biology. From a fundamental standpoint, the application of high pressure allows one to investigate the effect of volume on the properties of a material. It also allows for the examination of the conversion of one phase of matter to another, whether through the crystallization of a material under high pressure, or the transformation of a solid from one crystal structure to another. This dissertation explores the properties of nanoscale materials under high pressure. The size dependence for solid-solid phase transitions in II-VI nanocrystals under high pressure has been previously investigated. Nanoparticles represent an important size regime where the surface atoms make up a significant percentage of the total atoms in the crystal. This leads to the surface playing a larger role in the thermodynamics of the phase transition in these nanocrystals. The first part of this dissertation examines the effect of small changes in the structure of the nanomaterial on its high pressure behavior. By changing the surface of cadmium selenide nanocrystals through the introduction of a zinc sulfide shell, it was determined that the phase transition could be tuned for shell thicknesses below the critical thickness. In addition to structural phase transitions in this core/shell system, the optical properties under high pressure were also investigated. The fluorescence of the core/shell particles splits into multiple peaks due to a breaking of the crystal symmetry and spin exchange in the excitons under pressure. This theme was continued through the investigation of bismuth selenide nanoribbons with and without copper intercalated into the lattice. Bismuth selenide has been found to be a topological insulator, while copper bismuth selenide is a superconductor. The phase transition from the layered rhombohedral structure to the monoclinic phase in bismuth selenide nanomaterials could be pushed to higher pressures through the intercalation of copper in the van der Waals gap between the crystal layers. The dissertation continues by exploring the mechanism of the wurtzite to rocksalt phase transition in cadmium sulfide nanocrystals on ultrafast timescales. A shock wave was initiated through the sample using a laser and the phase transition was probed using an ultrafast X-ray probe pulse. This allowed for the collection of the necessary structural data from the diffraction patterns at different time delays. A h-MgO type intermediate was found to be present under lower shock stresses, but it was not observed at higher shock stresses. This indicates that multiple phase transition pathways are simultaneously occurring in the sample. Steps towards achieving the ability to image the fluorescence of single semiconductor nanoparticles under high pressure are discussed. At a single particle level new phenomena have been observed due to the inherent heterogeneity of the sample and a lack of averaging over multiple events. There are many hurdles that must be overcome before such experiments can be achieved. The last part of the dissertation discusses the use of the high pressure behavior of these semiconductor nanocrystals to sense forces in a biological sample. The spectral shift of tetrapod nanocrystals was used to quantify the force exerted on a substrate by beating HL-1 cardiomyocytes. This was performed through the use of an acousto-optic tunable filter to provide the measurements with spectral, temporal, and spatial resolution. Through the investigation of the fundamental properties of nanomaterials under high pressure, a better understanding of these materials, including their thermodynamics, was obtained. As a result, new applications of these materials to fields such as force sensing are discussed and implemented

A Nanocrystal Sensor for Luminescence Detection of Cellular Forces

Quantum dots have been used as bright fluorescent tags with high photostability to probe numerous biological systems. In this work we present the tetrapod quantum dot as a dynamic, next-generation nanocrystal probe that fluorescently reports cellular forces with spatial and temporal resolution. Its small size and colloidal state suggest that the tetrapod may be further developed as a tool to measure cellular forces in vivo and with macromolecular spatial resolution

Metastability in Pressure-Induced Structural Transformations of CdSe/ZnS Core/Shell Nanocrystals

The kinetics and thermodynamics of structural transformations under pressure depend strongly on particle size due to the influence of surface free energy. By suitable design of surface structure, composition, and passivation it is possible, in principle, to prepare nanocrystals in structures inaccessible to bulk materials. However, few realizations of such extreme size-dependent behavior exist. Here, we show with molecular dynamics computer simulation that in a model of CdSe/ZnS core/shell nanocrystals the core high-pressure structure can be made metastable under ambient conditions by tuning the thickness of the shell. In nanocrystals with thick shells, we furthermore observe a wurtzite to NiAs transformation, which does not occur in the pure bulk materials. These phenomena are linked to a fundamental change in the atomistic transformation mechanism from heterogeneous nucleation at the surface to homogeneous nucleation in the crystal core

Metastability in Pressure-Induced Structural Transformations of CdSe/ZnS Core/Shell Nanocrystals

The kinetics and thermodynamics of structural transformations under pressure depend strongly on particle size due to the influence of surface free energy. By suitable design of surface structure, composition, and passivation it is possible, in principle, to prepare nanocrystals in structures inaccessible to bulk materials. However, few realizations of such extreme size-dependent behavior exist. Here, we show with molecular dynamics computer simulation that in a model of CdSe/ZnS core/shell nanocrystals the core high-pressure structure can be made metastable under ambient conditions by tuning the thickness of the shell. In nanocrystals with thick shells, we furthermore observe a wurtzite to NiAs transformation, which does not occur in the pure bulk materials. These phenomena are linked to a fundamental change in the atomistic transformation mechanism from heterogeneous nucleation at the surface to homogeneous nucleation in the crystal core

Metastability in Pressure-Induced Structural Transformations of CdSe/ZnS Core/Shell Nanocrystals

The kinetics and thermodynamics of structural transformations under pressure depend strongly on particle size due to the influence of surface free energy. By suitable design of surface structure, composition, and passivation it is possible, in principle, to prepare nanocrystals in structures inaccessible to bulk materials. However, few realizations of such extreme size-dependent behavior exist. Here, we show with molecular dynamics computer simulation that in a model of CdSe/ZnS core/shell nanocrystals the core high-pressure structure can be made metastable under ambient conditions by tuning the thickness of the shell. In nanocrystals with thick shells, we furthermore observe a wurtzite to NiAs transformation, which does not occur in the pure bulk materials. These phenomena are linked to a fundamental change in the atomistic transformation mechanism from heterogeneous nucleation at the surface to homogeneous nucleation in the crystal core