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.]

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.

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