A virtual screening approach to identifying the greenest compound for a task: application to switchable-hydrophilicity solvents

Abstract

A virtual or in-silico screening approach makes it much easier to identify the molecular structure that best combines efficacy for a specific task with safety and minimum environmental or health impacts. In this approach, software is used to generate a larger number of possible molecular structures and then to use QSARs (quantitative structure-activity relationships) to predict properties related to performance, safety, and health and environmental impact. The structures are are then given scores on criteria (such as flash point or toxicity) and an overall score. The method identifies compounds that have high scores for the 3 performance criteria and 7 health, safety, and environmental criteria. This method allows for larger-scale and faster screening than can be performed using human intellect and a benchtop approach. The success of this approach is demonstrated by its application to the identification of new and possibly greener switchable-hydrophilicity solvents (SHS). Three SHS were identified using this method. This approach to molecular design is entirely modular and can be applied to the design of almost any type of chemical. However, limitations of the method include the fact that it does not take into consideration the health and environmental costs of manufacturing the chemical.

Diamines as switchable-hydrophilicity solvents with improved phase behaviour

“… c Extrapolated from a reported boiling point under reduced pressure reported using a nomograph. 37 d Data from a safety data sheet provided by Sigma-Aldrich. …”

“…This compound was identified using a virtual screening process similar to a process developed for monoamine SHSs. 37 For details on this process, see the ESI. † Diamine 4 is preferable to every other diamine SHS in every category except Daphnia magna LC 50 and bioaccumulation factor, where it is comparable to the other diamine SHSs.…”

“…An evaluation of the prediction accuracy of TEST for amines has been performed in previous studies of monoamine SHSs. 31,37 Some predictions, such as boiling and ash points, are reasonably accurate (usually within 10 C of the experimental value), but other predictions are not as accurate. For example, predicted LD 50 (oral, rat) values for amines were found to be within a factor of 3 of the experimental values 95% of the time.…”

Green and Sustainable Solvents in Chemical Processes

“…Vanderveen et al have demonstrated a virtual screening approach to identify tertiary amines that act as SHS with consideration to environmental impact, health, and safety (EHS). 463 Amines were first identified by generating a library of molecular structures and predicting both their performance properties (log K ow , pK aH , and melting point) and their EHS properties (oral LD 50 , LC 50 , bioaccumulation factor, flash point, vapor pressure, and boiling point). Parameter restrictions were used to filter out the generated structures to provide amines with the best characteristics for a SHS.…”

Hybrid Extraction of Oily Sludge by Tertiary Amines and Protonated Tertiary Amines

“…The advantage of TA is that they can be recycled, without any change of performance [20,37,38]. In general, with bubbling of N 2 at 60°C, the PTA could be switched reversibly to a hydrophobic form TA.…”