Advancing the CLASSIC NMR Strategy to Understand Fundamentals of Crystallization Processes

The PhD project aims to develop, optimize and apply the CLASSIC NMR strategy to gain new insights into a range of crystallization systems.

This will include research in the following fields:
•(i) pharmaceutical crystallization processes
•(ii) materials implicated in biomineralization (focusing on calcium carbonate and calcium phosphates)
•(iii) assembly of metal-organic frameworks (MOFs)
•(iv) formation of polymer materials.

The project will be structured to focus on area-(i) within Year-1 [as area-(i) is closest to the types of organic crystallization studied by CLASSIC NMR to date], progressing to include area-(ii) in Year-2, and expanding the portfolio to encompass area-(iii) and area-(iv) in Year-3, ensuring completion of a significant amount of original research within the 3.5 year timeframe.

Background

While crystallization processes are critically important in many aspects of chemical, pharmaceutical and biological sciences, the fundamental factors that control crystallization mechanisms remain poorly understood.

To address this issue, the development of in-situ experimental methods that allow time-resolved monitoring of such processes offer the most encouraging prospects. With this motivation, one of the main research themes in the Harris group is the development and application of new in-situ solid-state NMR strategies for mapping the time-evolution of crystallization processes, with the aim of unravelling the sequence of solid phases (e.g. amorphous phases, polymorphs, solvates) formed as a function of time during crystallization and elucidating kinetic information.

In 2008, we reported the first in-situ solid-state NMR studies of crystallization, and in 2014 we developed a significantly more powerful in-situ NMR strategy called CLASSIC NMR (Combined Liquid And Solid-State In-situ Crystallization NMR), which allows simultaneous measurement of both liquid-state and solid-state NMR spectra as a function of time during crystallization.

This technique yields insights into the complementary changes occurring in the solid and liquid phases during crystallization from solution, and is now the standard protocol for in-situ NMR studies of crystallization mechanisms.

Project aims and methods

During the first four months of the PhD programme, you will receive specific training (both from the supervisor and from the senior PDRA in his group) in the research skills required to carry out the research project, specifically training in:
•the theory and application of solid-state NMR
•experimental aspects of solid-state NMR instrumentation (both in Cardiff and at the UK National High-Field Solid-State NMR Facility)
•methods for processing and interpretation of solid-state NMR data
•general techniques for preparation of materials by crystallization
•techniques for basic characterization of materials (primarily powder XRD), and
•training in computational techniques for analysis of solid-state NMR data (including periodic-DFT methods for calculating NMR properties of solids).

The combination of skills acquired from these training aspects is essential to enable you to make rapid progress in the PhD project. You will also receive general advice and training in:
•safe laboratory practice
•recording
•organization and appraisal of scientific data
•careful planning and prioritization of activities and efficient execution of work plans
•preparation of presentations (oral, PowerPoint, written reports and poster presentations) for effective dissemination of the results and conclusions of the research.

Start date: 1st October 2019

Supervisor: Professor Kenneth Harris - https://www.cardiff.ac.uk/people/view/38526-harris-kenneth