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Exploring parameters that influence resin swelling in green solvents

   Department of Chemistry

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  Dr A Routledge, Prof M North  No more applications being accepted  Competition Funded PhD Project (UK Students Only)

About the Project


Solid-phase peptide synthesis (SPPS) and solid-phase organic synthesis (SPOS) are key enabling tools in organic chemistry. Their common denominator is the solid-phase, typically cross-linked polystyrene (PS). For chemistry using PS beads the solvent has to solvate (swell) the resin to allow reaction to proceed; this typically requires the use of very ‘ungreen’ solvents such as DMF and dichloromethane.


There is extensive interest in the development of replacements for conventional solvents which have low toxicity and are sustainably sourced. Our aim is to build on our empirical data bank in the area of functionalised polymer compatibility with sustainable solvents and to develop a deeper, translatable understanding of the underlying chemical principles involved in this process.

This project will involve organic chemistry (SPPS/SPOS) and modelling studies (HSPiP) to produce a package that will allow prediction of the optimum sustainable solvent for each step of a synthesis involving a specific solid-phase component. This will provide a step change as traditionally a single solvent has been used for each step in a multistep solid-phase reaction based only on resin swelling.

Experimental Approach:

Our approach requires the generation of a ‘training sets’ of experimentally derived data for modelling studies which is why this project will start with experimental data generation. SPPS will be used to prepare threonine containing peptides (2-9 amino acids in length) attached to both polystyrene and PEG resins. How the position and number of free OH groups in the resin-peptide system influences swelling in alcoholic solvents (MeOH to hexan-1-ol) will be probed. Once the experimental data is generated, HSPiP software will be used to model the resin-alcoholic solvent interactions in terms of the relative importance of each Hansen solubility parameter and to develop resin swelling guidelines based on the Hansen solubility parameters (year 1). There will then be a feedback loop; the results from one set of experimental reactions will inform the design of the proceeding set in terms of peptide design and solvent chosen. Once a working HSPiP model is obtained, it will be verified through application to the SPPS of biologically active peptides such as bradykinin and to SPOS of multicomponent reactions e.g. Biginelli and Ugi reactions (year 2). The protecting groups and activating agents used in SPPS are optimised for use in DMF, so the final stage of this project will be to investigate the use of alternatives which are more compatible with the green solvent systems developed in this work (year 3).


This project is extremely timely with the impetus to replace solvents that will be banned or severely restricted. There is, no precedent to our approach to optimal solvent identification. This project could significantly ‘fast forward’ the adoption of sustainable solvents in the chemical industry with subsequent benefit to human health, the environment, the UK economy and business. It will also provide an exemplar of the adoption of circular economy principles.


Solvents are critical to the chemistry carried out by the pharmaceutical sector both in solution and on the solid-phase. Any work showing that non-toxic alternatives can be used as replacements for traditional polar aprotic solvents will be of significant interest as will the ability to design a solid-phase synthesis with not only the reagents but optimal sustainable solvent(s) for each step of the synthesis. The project will give the student opportunities to interact/collaborate with interested industry.

The project is multi-disciplinary and will provide excellent lab-based training as it involves a wide range of techniques encompassing synthetic chemistry and using HSPiP software. In addition, the student will participate in the chemistry department’s postgraduate training. They will take a selection of suitable training courses which, depending on their background, will complement lab-based training. All Chemistry research students have access to our innovative Doctoral Training in Chemistry (iDTC): cohort-based training to support the development of scientific, transferable and employability skills:

The Department of Chemistry holds an Athena SWAN Gold Award and is committed to supporting equality and diversity for all staff and students. The Department strives to provide a working environment which allows all staff and students to contribute fully, to flourish, and to excel:

For more information about the project, click on the supervisor's name above to email the supervisor. For more information about the application process or funding, please click on email institution

This PhD will formally start on 1 October 2022. Induction activities may start a few days earlier.

To apply for this project, submit an online PhD in Chemistry application:

You should hold or expect to achieve the equivalent of at least a UK upper second class degree in Chemistry or a related subject.  

Funding Notes

Fully funded for 3 years by the Department of Chemistry and covers: (i) a tax-free annual stipend at the standard Research Council rate (£15,609 for 2021-22), (ii) tuition fees at the Home rate, (iii) funding for consumables. See guidance for further details:
Studentships are available to any student who is eligible to pay tuition fees at the home rate:
Not all projects will be funded; candidates will be appointed via a competitive process.


Candidate selection process:
• You should hold or expect to receive at least an upper second class degree in chemistry or a chemical sciences related subject
• Applicants should submit a PhD application to the University of York by 28 February 2022
• Supervisors may contact candidates either by email, telephone or web-chat
• Supervisors can nominate up to 2 candidates to be interviewed for the project
• The interview panel will shortlist candidates for interview from all those nominated
• Shortlisted candidates will be invited to a panel interview on 30th or 31st March or 1stApril
• The awarding committee will award studentships following the panel interviews
• Candidates will be notified of the outcome of the panel’s decision by email

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