The CHEM21 Metrics Toolkit


Following on from the introduction to the metrics toolkit that was developed by the CHEM21 consortium that was provided in Introduction to green metrics, in this video Louise Summerton provides a more detailed overview of the metrics toolkit and how it can be used to assess the greenness of a reaction via a comprehensive and holistic range of criteria.  

The rationale behind the creation of the toolkit and description of the methodologies adopted is available as an open access publication [1] and the Toolkit itself is available in the form of a user friendly excel spreadsheet in the supplementary information of the publication.


Zero Pass in More Detail

The CHEM21 Metrics Toolkit is specifically structured with a series of ‘passes’ to cover everything from bench top research right through to industrial scale with increasing level of complexity.  In this video Sarah Abou-Shehada at the Green Chemistry Centre of Excellence, University of York examines ‘Zero Pass in more detail.  Zero pass is aimed at the assessment of reactions at the discovery scale and provides an initial light tough appraisal for screening reactions (few mg scale).


Zero Pass Interactive Tool

You can use this interactive tool at the reaction discovery level. Click the elements of the chart below to proceed through the metric stages. The most promising reactions as indicated by your green metrics can then be taken to first pass and beyond.
Yield, Conversion and Selectivity
Considers limiting reactant and product
  • High yield is desirable
  • If yield is low but conversion is high- reaction requires optimisation
  • If yield is low and conversion is low- reaction requires redesign
Yield is high Yield low but selectivity high (low conversion) Yield low and selectivity low (high conversion)
Reaction can be optimized
>You need to return to your reaction and redesign it
Atom economy
Considers all reactants
Assumes 100% yield
  •  Atom Economy (AE) measures the efficiency of the reaction by the number of the atoms from the reactants that appear in the final product.
  • AE assumes 100% yield and stoichiometric loading
  • AE is an excellent metric to access the inherent efficiency of a reaction with respect to use of reactants- however is not great as a standalone metric
Atom economy high (≥ 62%) Atom economy low
Maximise incorporation of starting material into product (fewer wasted atoms).
Choose leaving groups to be as small as possible, avoid large protecting groups..
Reaction mass efficiency
Considers all reactants, stoichiometries and yield
The most efficient your reaction can be is if RME=AE
  • Reaction Mass Efficiency (RME) gives a fuller picture of reactant use. It is mass based and incorporates yield and stoichiometry
  • According to Andraos[citeneeded]: a reaction is only considered green when both the AE and RME are above 62%. In other words, if a reaction has an RME of ≥62% but an AE ≤62%, or vice versa, the reaction is not green.
  • However, if your AE and RME are much greater than the current state of the art, then you are well on your way to improving the green credentials of such transformations.
  • The AE provides the optimum efficiency your process can achieve; the closer the RME is to it, the closer the reaction is to its optimal efficiency.
RME (≥62%) ~ AE RME << AE
Try to reduce stoichiometric loading of reagents whilst monitoring yield
Reaction mass efficiency
Considers all reactants, stoichiometries and yield
The most efficient your reaction can be is if RME=AE
  • Reaction Mass Efficiency (RME) gives a fuller picture of reactant use. It is mass based and incorporates yield and stoichiometry
  • According to Andraos[citeneeded]: a reaction is only considered green when both the AE and RME are above 62%. In other words, if a reaction has an RME of ≥62% but an AE ≤62%, or vice versa, the reaction is not green.
  • However, if your AE and RME are much greater than the current state of the art, then you are well on your way to improving the green credentials of such transformations.
  • The AE provides the optimum efficiency your process can achieve; the closer the RME is to it, the closer the reaction is to its optimal efficiency.
RME (≥62%) ~ AE RME << AE
Try to reduce stoichiometric loading of reagents whilst monitoring yield
Health and safety
Red-flagged substances carry a serious physical, health or environmental risk
  • Screening for a broad range of reagents is also necessary at this stage and give a lot of insight into the chemical transformation
  • As such only the most severe hazard statements (red flag) are to be avoided at zero pass and must be substituted
No red flag Red flag
Use reagent replacement guides to identify a potential replacement
If not possible, must be justified!
  1. R. C. McElroy, A. Constantinou, L. C. Jones, L. Summerton and J. H. Clark, Towards a holistic approach to metrics for the 21st century pharmaceutical industry, Green Chem., 2015, 17, 3111-3121.