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Scientific Update - We've Got Chemistry!

24 January 2012

Co-Crystals

Written by Dr John Knight

Structure of CL-20

Those that work in the pharmaceutical industry will be very aware of the issues associated with final physical form, such as salt selection and polymorphism and its control.

The issue of co-crystals is one that crops up occasionally in the quest for suitable forms of APIs so I was interested to note this example as a reminder that, of course, the solid state is important in other fields of chemistry. A J Matzger et al (Angew Chem Int Ed, 2011, 50, 8960) describe a co-crystal between the relatively new energetic material CL-20, which is shock sensitive, and the well known explosive TNT. One might be forgiven for thinking this is a recipe for disaster – a co-crystal of one explosive material with another?

In fact, the paper introduces the subject very nicely for those of us not accustomed to design of such materials, indicating that past attempts to stabilise explosives as co-crystals with non-energetic partners can work, but inevitably results in dilution of the energetic component and hence reduction in explosive power. This co-crystal between two energetic materials realises benefits in terms of enhanced stability/reduced shock sensitivity but of course maintains the explosive power. A further specific feature is that on heating the co-crystal, at a certain point the TNT liquefies and on cooling the input co-crsytal is not regenerated, but instead the mixture is again shock sensitive, thereby presenting an opportunity to use this strategy to design materials with improved handling characteristics for transport which can be altered at the point of use.

For interest, the structure of CL-20 is illustrated above.

About the Author

Dr John Knight

John Knight gained a first class honours degree in chemistry at theUniversity of Southampton, UK. John remained at Southampton to study for his PhD in synthetic methodology utilizing radical cyclisation anddipolar cyloaddition chemistry. After gaining his PhD, John moved to Columbia University, New York, USA where he worked as a NATOPostdoctoral Fellow with Professor Gilbert Stork. John returned to theUK in 1987 joining Glaxo Group Research (now GSK) as a medicinalchemist, where he remained for 4 years before moving to the processresearch and development department at Glaxo, where he remained for afurther 3½ years. During his time at Glaxo, John worked on a number ofprojects and gained considerable plant experience (pilot andmanufacturing). In 1994 John moved to Oxford Asymmetry (later changingits name to Evotec and most recently to Aptuit) when it had just 25staff. John’s major role when first at Oxford Asymmetry was to workwith a consultant project manager to design, build and commission asmall pilot plant, whilst in parallel developing the chemistry PRDeffort at Oxford Asymmetry. The plant was fully operational within 18months, operating to a 24h/7d shift pattern. John continued to run thepilot plant for a further 3 years, during which time he hadconsiderable input to the design of a second plant, which was completedand commissioned in 2000. After an 18-month period at a smallpharmaceutical company, John returned to Oxford in 2000 (by now calledEvotec) to head the PRD department. John remained in this position for6.5 years, during which time he assisted in its expansion, establisheda team to perform polymorph and salt screening studies and establishedand maintained high standards of development expertise across thedepartment. John has managed the chemical development and transfer ofnumerous NCE’s into the plant for clients and been involved in processvalidations. He joined Scientific Update in January 2008 as Scientific Director.

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