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In the present work, various objective functions were formulated and optimized using the mixed integer nonlinear programming and the generalized reduced gradient nonlinear method from the solver tool of Microsoft® Excel 2016, respectively. The CH3FO2, C2H4F2O, CH2F2O2, CH2F2O, C3H4F2, and the C2H2F2O molecules were found to meet structural feasibility constraints and physical properties from refrigerant molecules and have not previously been reported in the literature. These new refrigerants present global warming potential values similar to that from the R-134a and Freon 12 refrigerants and null ozone depletion potential. Moreover, these molecules are normally flammable, as similar as to R-134a refrigerant. The CH3FO2, C2H4F2O, CH2F2O2, C2H2F2O, and CH2F2O show toxicity values similar to R-134a and Freon 12 refrigerants.