Green organocatalysis: an (eco)-toxicity and biodegradation study of organocatalysts
Hayes, Thomas (2012) Green organocatalysis: an (eco)-toxicity and biodegradation study of organocatalysts. PhD thesis, Dublin City University.
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A series of novel (a)chiral substituted BINOLs and achiral biquinoline compounds were synthesised and characterised. Different substituents were incorporated within the structure of these molecules to enhance biodegradation. These substituents were selected according to Boethling’s ‘rules of thumb’ for designing biodegradable chemicals.
Final novel compounds were screened for antimicrobial activity and tested for biodegradation. As well a number of known organocatalysts were also studied for antimicrobial activity, tested for biodegradation and cytotoxicity, apoptosis and cell viability studies were performed against three blood cell lines. Both enantiomers of amino acids (L and D) and BINOLs (S and R) were screened for anti-microbial activity to determine the affect of stereochemistry. Antimicrobial studies were performed using the minimum inhibitory concentration assay. Highest concentration was dependant on chemical solubility, however, for most compounds tested the highest concentration was 2 mM. Test organisms used for this study included fungi, Gram positive and Gram negative bacteria. Growth inhibition of microbes was noted for some compounds within tested concentration range. (R)-3,3’-Dibromo-H8-BINOL was found to be a hit antimicrobial agent for Gram positive bacteria with an MIC value in the low micromolar range.
Cytotoxicity, apoptosis and cell viability studies of organocatalysts were carried out against the blood cell lines human erythroid progenitors, HL-60 and K-562 using the
promega protocols, respectively. A Maruoka phase-transfer catalyst was found to reduce cell viability and promote apoptosis for all three cell lines studied.
Biodegradation studies of organocatalysts were performed using the CO2 headspace test (ISO 14593). BINOL and derivatives showed poor biodegradation under the parameters
of the CO2 headspace test (ISO 14593). L-Prolinamide passed the CO2 headspace test (ISO 14593) and can be classified as a readily biodegradable catalyst. For the inhibitory control biodegradation assay, a Maruoka phase-transfer catalyst was found to have an inhibitory effect on the activity of the inoculum. All other organocatalysts studied,
showed low inhibition for the inhibitory control biodegradation assay.
Chiral substituted BINOLs were synthesised and evaluated as asymmetric catalysts for the Morita-Baylis-Hillman reaction. For this study, test substrates hydrocinnamaldehyde and 2-cyclohexen-1-one were reacted together in the presence of triethylphosphine in THF and BINOL derived catalysts (2 mol%) in THF at room temperature. However, preliminary results show catalysts performed poorly when compared to known optimal catalyst.
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