Tudor Grecu

• Project management for international solid state and crystallization development projects • Define work packages, delegate, coordinate, engage and motivate project team members • Act as main point of contact between customers and various scientific departments • Identify departmental improvement areas and implementing novel ways of working to expand the company’s scope and capabilities

• Mentoring other scientists in solid state and crystallisation development • Working at the interface between early chemical and product development • Responsible for designing and optimising crystallisation processes for APIs and ensure their robustness from lab scale to pilot plant manufacture • Fine tuning particle properties to ensure they are suitable for Phase I to III formulation and processability • Developed isolation and filtration procedures and carried out particle characterisation on resulting material • Superuser in the application of PAT techniques for measuring and controlling critical reaction parameters • Supporting crystallisation of intermediates along all steps of synthetic route development Expertise in key crystallisation techniques such as seeded cooling, anti-solvent and reaction crystallisations, measuring solubility and solubility curves, Crystal Breeder, Crystal 16, Crystalline, Focused Beam Reflectance Measurement, Particle Vision Microscope, ATR-IR and UV, design of experiments, controlled reactors such as EasyMax, OptiMax and jacketed vessels, morphology analysis.

• Lead solid state scientist on a number of oncology, respiratory and cardiovascular projects with a focus on timed delivery and patient safety • Deal with polymorphic issues by optimising solid state properties through salt/cocrystal formation • Team player managing and influencing solid form selection for candidate drug development and scale-up • Constantly thriving to improve ways of working through internal research • Involved in external collaborations, mentoring PhD students, summer students and colleagues • Instrument owner for all XRPD instruments on site: training, RPS, calibrations, radiation checks, troubleshooting, servicing • Author of several patents and peer-reviewed publications • Established strong working interactions with Sweden during a 2-month secondment on the Molndal site Expertise in key solid state techniques such as X-ray Powder Diffraction, Single Crystal X-ray Diffraction, Polarised Light Microscopy, Differential Scanning Calorimetry, Thermogravimetric Analysis, Dynamic Vapour Sorption, NMR Spectroscopy, Infra-red Spectroscopy and Raman Spectroscopy

• Teamplayer in a world leading Contract Research Organisation, with a goal of providing the pharmaceutical industries with drug development and testing • Undertake polymorph, salt and cocrystal screens for compounds at different stages in the solid form development process • Analysis and characterisation of client samples in compliance with the ISO 9001 standards • Multitasking and time management were essential for running several projects simultaneously and preparing frequent slide packs, updates and client reports • Liaise with clients through teleconferences to understand their requirements, plan and present results and receive feedback

• Compiled a database of almost 2000 salt and cocrystal formers to be used for virtual screening of any compound of pharmaceutical interest • Divided the database into smaller libraries containing only GRAS and EAFUS compounds, or separate lists of solid and liquid coformers • Virtual cocrystal screening to predict which coformers are the most suitable candidates for API cocrystallisation based on the difference in energy between the cocrystal and the sum of its two components

Thesis title: Virtual Cocrystal Screening During my PhD, I have gained skills in both computational and experimental solid state chemistry. My work has been been focused on developing and improving a virtual screen to predict the probability of cocrystal formation. Experimentally, I have been growing single cocrystals of active pharmaceutical ingredients (APIs) with potential crystal coformers in order to validate the methodology. Main achievements: • The development of a virtual screen to predict the probability of cocrystal formation based on the difference in interaction site pairing energies (ΔE) between supramolecular complexes without empirical parameterisation • Used ab initio methods to predict the thermodynamic properties of non-covalent interactions from molecular electrostatic potential surfaces of cocrystal components • Several relevant molecular descriptors were tested and the cocrystal prediction was improved. • Experimentally identified new cocrystals and solvate forms of low solubility APIs based on selection of potential coformers from extensive databases • Acted as a laboratory supervisor for groups of undergraduate students of physical organic chemistry on their second and third year research projects

• Synthesized derivatives (racemic and enantiopure) of phenylalanine familiarizing myself with a variety of reactions such as Knoevenagel-type condensations, Mannich reactions, hydrogenations, conjugate additions, protection and deprotection of ammonia moieties • Used both PAM (Phenylalanine aminomutase) and PAL (Phenylalanine ammonia lyase) to furnish chiral β-amino acids from corresponding cheap non-chiral cinnamic acid derivatives • Substrate specificity of derivatives was tested with the above mentioned enzymes using a colorimetric assay and enzyme kinetics were determined by HPLC

BSc Research: 'The study of artificial oligomers' - synthesis of starting materials for polymer and biomimetic chemistry to yield aromatic acids and esters as products. MChem Research: 'Cooperativity in hydrogen bonding interactions' - investigated the effect of molecule rigidity on cooperative effects in systems capable of multiple hydrogen bonds by varying hydrocarbon chain length in a model system. 1H NMR titration experiments were used to measure binding constants for the different systems.