Stereoselective biotransformation of β-blockers and antidepressants in the aquatic environment Edmond Sanganyado & Jay Gan Department of Environmental Science, University of California Riverside

-Rachel Carson, Silent Spring In river or lake or reservoir - or for that matter in the glass of water served at your dinner table - are mingled chemicals that no responsible chemist would think of combining in his laboratory. -Rachel Carson, Silent Spring Griswold, Eliza. "How'Silent Spring'Ignited the Environmental Movement." The New York Times (2012): 5-7.

Pharmaceuticals in the Environment We spray our elm trees and the following springs are silent of robin song—not because we sprayed the robins directly, but because the poison traveled. Rachel Carson, Silent Spring 5-90% pharmaceuticals are excreted as parent compound. Pharmaceuticals are not efficiently removed in wastewater treatment plants. Pharmaceuticals pose human and environmental risk to non-target species.

Chirality in Pharmaceuticals >50 % pharmaceuticals are chiral in nature Propranolol: a beta-blocker S(–) is ≈ x100 more potent than R(+) in blocking beta adrenergic receptors

Implications of Chirality Chiral molecules exhibit stereoselectivity in chiral environments. Stereoselective Interaction Stereoselective biodegradation and/or toxicity Overlooking the stereochemistry of pharmaceuticals can be catastrophic like the thalidomide tragedy.

Effect of Chirality on Environmental Risk Assessment Toxicity: LC50, NOEC, etc. Toxicity usually stereoselective Hazard Assessment Bioaccumulation Potential: log Kow Bioaccumulation might be stereoselective Exposure Assessment Persistence: Kd and T1/2 Biodegradation usually stereoselective

Fate of Pharmaceuticals in the Environment Source, occurrence and fate of chiral pharmaceuticals Objectives: 1 To determine the effect of chirality on degradation of atenolol and fluoxetine in river water. To determine whether biotransformation of beta blockers in WWTP is stereoselective. 2

Stereoselective biodegradation of chiral pharmaceuticals Microcosm experiments Extraction, SPE HLB cartridges Chirobiotic V column Optimize pH, chaotropic salts and flow rate 8 mM ammonium acetate and 0.005% formic acid in methanol E. Sanganyado, Z. Lu, J. Gan Mechanistic insights on chaotropic interactions of liophilic ions with basic pharmaceuticals in polar ionic mode liquid chromatography, J. Chromatogr. A, 1368 (2014), pp. 82–88

Stereoselective biodegradation of Fluoxetine in river water Enantiomeric Fraction= [R]/([R] + [S] Stanley, J. K., Ramirez, A. J., Chambliss, C. K., & Brooks, B. W. (2007). Enantiospecific sublethal effects of the antidepressant fluoxetine to a model aquatic vertebrate and invertebrate. Chemosphere, 69(1), 9-16.

Stereoselective biodegradation of atenolol in river water De Andrés, F., Castañeda, G. and Ríos, Á. (2009), Use of toxicity assays for enantiomeric discrimination of pharmaceutical substances. Chirality, 21: 751–759.

Stereoselective biodegradation of chiral pharmaceuticals in wastewater

? ? Further Research Risk Assessment Toxicity: LC50, NOEC, etc. Toxicity usually stereoselective Hazard Assessment ? Bioaccumulation Potential: log Kow Bioaccumulation might be stereoselective Exposure Assessment Persistence: Kd and T1/2 Biodegradation usually stereoselective

Conclusion determination of enantiomeric composition and enrichment in different environmental matrices help to improve accuracy in exposure assessment. Read-across model is a useful tool in predicting effect factor of chiral pharmaceuticals. Additional studies are necessary for understanding stereoselectivity in bioaccumulation uptake of chiral pharmaceuticals in aquatic organism

Acknowledgements Thank You Members of Gan Lab Special thanks to: 1 Dr. Jay Gan. Members of Gan Lab Fulbright Fellowship Program ETOX Program 2 3 4 Thank You Awesome people