Efficiency, toxicity, explosiveness, cost and flammability must all be considered. On the extreme ends of flammability hazard is hydrocarbons while toxicity would be ammonia and SO2.
As awesome as it would be, we don't have the almighty fluid.
HFO-1234yf and HFC-32 are in consideration, however they're not perfect as they have A2L flammability classification even though they're not as dangerous as hydrocarbons. They require much higher concentration, higher ignition energy to ignite and do not propagate explosively like gaseous hydrocarbons.
I don't believe there's a silver bullet. The use of existing stock and reclaimed HCFC-22 remains legal for service.
There are plethora of approved replacements, but I'm not sure which one we should settle down on yet. I don't believe there's been extensive testing done using tailored equipment.
New equipment have migrated to R-410A. R-32 could possibly substitute it.
Any blend and new refrigerants are subject to patent dictated pricing including the R441A/HCR188C .
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