Development of crystalline and polymeric materials for stimuli-responsive and biomedical applications
Creators: name: Tiba, Aladen
Publisher: name: University of Iowa
Year: 2024
Subjects: Pharmaceutical sciences
public abstract

description: Crystal engineering is important for the design of materials and devices with targeted physical properties. Control of crystal size, morphology, and intermolecular interactions of the lattice, dynamic and static, enables precise engineering of the material’s bulk properties such as adsorption, bioavailability, or elasticity using reversible chemical bonds. For example, the crystal packing and hence the crystallite size may be modified by altering the synthesis conditions or including a modulator without creating or breaking covalent bonds. Such atomic and nanoscale modifications in turn significantly affected the adsorption and mechanical properties of one class of absorbent material, soft porous crystals such as metal-organic frameworks (MOFs), used in a variety of applications in fluid separation and chemical sensing due to their modularity and high selectivity.
description: This thesis represents the first study to demonstrate size-dependent mechanical properties of MOFs, determined by atomic force microscopy (AFM) nanoindentation. The results showed that reducing crystal size to the nanoscale can result in increased or decreased Young’s modulus depending on the system under study. The observed change in mechanical properties explains previously reported size-dependent variations in gas adsorption of ZIF-8. The study demonstrates how downsizing crystalline metal-organic materials can lead to specific and adjustable physical properties. We also show how a combination of techniques including AFM nanoindentation, scanning electron microscopy energy dispersive X-ray spectroscopy, IR spectroscopy, and gas physisorption analysis can enable correlations between intermolecular structure, bulk elasticity, and the gas adsorption behavior of materials. Using highly basic triethylamine during the synthesis of ZIF-8 leads to a lower number of interframework hydrogen bonds and a higher number of missing linker defects, which play an integral role in the observed mechanical and gas adsorption anomalies.
description: The thesis also demonstrates that the size-dependent mechanical phenomena are widespread across a broad category of MOFs. Soft porous nanocrystals of the structure [Cu2(bdc)2(bpy)]n with a shape-memory effect have been shown to exhibit a significant increase in elastic modulus when compared to their microcrystalline counterparts. These findings suggest that crystal downsizing is a promising strategy for tailoring the mechanical properties of MOFs, opening new avenues for their use in a variety of applications.
description: Moreover, a novel AFM nanoindentation methodology is developed to determine the hardness of nanomaterials. The technique is developed on nanocrystals of acetylsalicylic acid using atomic force microscopy (AFM) nanoindentation. The results show that the nanocrystals exhibited a transition from elastic to plastic deformation, and the values of Young’s modulus and hardness for aspirin nanocrystals were found to be approximately 3 GPa and 0.3 GPa, respectively. This study highlights the successful implementation of the AFM nanoindentation technique in accurately determining the hardness of nanomaterials at sub 100 nm indentations.
description: Related to biomedical defense applications, we discuss the challenge of maintaining dental and medical readiness in the military due to dental caries. To combat this issue, dental restoratives are a simple and effective solution and can be used as self-applied first aid. The study aims to evaluate the shear bond strength of two dental restorative materials to human teeth with two different fluoride treatments, as well as the hardness and biofilm formation on teeth after fluoride varnish application. The findings indicate that the combination of silver diamine fluoride with light cured methacrylate dental resins and resin-modified glass ionomer cements is a promising treatment option for dental caries in military settings.
description: Intermolecular interactions are the fabric of co-crystals formed from two or more molecules. Pharmaceutical co-crystals offer enhanced drug properties and multimodal capability by stabilizing one or more active pharmaceutical ingredient (API) with co-crystal formers (coformers) in the solid state. Varying the coformers of the target API(s) allows the control of noncovalent interactions (e.g., hydrogen bonds, π-effects, electrostatic forces) between atoms in the co-crystal lattice. Increased quantity and magnitude of intermolecular forces in the co-crystal compared to the individual component leads to increased stability, bioavailability, and controllable release of API. Here, we develop an approach to developing a topical form of tranexamic acid (TXA) in the form of a cocrystal. Four different cocrystals of TXA were synthesized and the coformers tested for their individual contribution to cytotoxicity and antimicrobial activity. The 1:1 cocrystal of TXA and gallic acid (GAA) was found to be a promising candidate for drug development due to its ability to induce blood clot formation and enhanced antibacterial activity. An optimized form of the TXA-GAA cocrystal has the potential to be incorporated into a solid form for use in a topical medical device, providing slow or extended release of the API.