What was I asked during my medicinal chemistry viva?

One of the most useful ways I prepared for my viva was by asking people who worked on similar PhD projects about their vivas and what they were asked. Below is a detailed but non-exhaustive list of questions and concepts I vaguely remember talking about during my viva. I hope it is useful as a guide for any current medicinal chemistry PhD students out there!

[Disclaimer: these questions are very specific and have quite a lot of jargon in them – apologies, but I put them in this post on purpose. PhDs involve you becoming an expert in a niche subject so I’d only expect another medicinal chemist googling for viva tips like I was a couple of months ago to find some of the actual content useful, however I hope more generally it shows what the process of the viva involves.]

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Introduction

• Target-based vs. probe-based strategies in drug discovery – essentially talking through my first figure
• Differences between a chemical probe and a drug
• Different criteria in the literature for what makes a good chemical probe
• Should you develop a probe with in vivo studies in mind?
• Starting points in a drug discovery project (literature screen, in silico screen, fragment screen, HTS library screen, patent hopping), advantages and disadvantages of all these techniques
• Target protein’s location in cells and if ubiquitous expression is of concern for it being a drug target of interest
• Importance of selectivity in early phase/late stage drug discovery
• Techniques for identifying disease targets (mice knockouts, cell knockouts, induced knockouts)

Results chapters

• Whether I did the computational chemistry (I did!)
• Usefulness of the molecular docking I did
• Why I used the software I did
• Role of DMAP in a particular reaction
• Drawing the chemical structure of DMAP
• How I would correct my schematic of a palladium-catalysed cycle (cringe!)
• Examples of more advanced Pd-catalysts
• The two mechanism theories currently proposed for Suzuki-Miyaura coupling reactions
• What the Z-value stands for in my assay data and how it was calculated
• How a particular assay worked (DiscoverX KINOMEscan)
• Discrepancies in TR-FRET data
• Identifying and describing an SN2-type reaction
• Geometry of transition state in SN2 reactions
• Drawing the reaction energy profile of an SN2 reaction
• Solubility of my compounds
• Ligand efficiency of my compounds

General questions

• If I found the international collaboration involving my project worked well
• What I’d do next

Experimental methods chapter

• Why I saw two peaks for a particular bond in an IR spectra (stretch/bend)
• Stereochemistry assignment of one of the chiral centres of one of my compounds – asked to name Carr Ingold Prelog rules used to do this
• Diastereotopic protons
• Double checking NMR assignments (some doublets were actually just very close singlets)

Other things I revised that didn’t come up

• pKa values of important protons in all reactions
• LogP values of my compounds
• All reaction mechanisms
• Being able to draw all the abbreviated chemical structures in my thesis
• Structures of amino acids
• How all assays worked
• Roles of reagents
• Alternative reagents/reactions – but not every example under the sun!
• Enzyme kinetics, deriving Mendel-Michaelis equation etc.
• The difference between IC50/Ki etc.
• When examples of FDA approved drugs and other compounds I’d given were approved, what they treated and how they were made
• Polar surface area of all compounds
• Overview of how chemical analysis techniques worked (e.g. NMR, mass spectrometry)
• Reasons for going in particular directions with the project
• Work by my examiners

This all might be way too specific for the average reader of this blog but it’s the sort of stuff I wanted to know before my viva about how someone else’s had gone.