= Phosphorothioate diastereomer
A \b[phosphorothioate diastereomer] is a stereochemical form of a <phosphorothioate substitution> that differs in configuration without changing connectivity. In a nucleic-acid phosphate joining different nucleotide environments, replacing a non-bridging <oxygen> with <sulfur> can make <phosphorus> a stereogenic center. The resulting $R_P$ and $S_P$ forms have the same elemental composition but a different spatial arrangement at that center.
They are <diastereomers> in the usual nucleic-acid context because the rest of the RNA already contains fixed stereochemistry, including its <ribose> units. Changing one phosphorus configuration while preserving those other centers does not produce the mirror image of the entire RNA. It is therefore misleading to call such a pair <enantiomers> merely because one phosphorus label changes from R to S. Assignment of the labels uses the <Cahn-Ingold-Prelog priority rules>, not the order in which a nucleotide sequence is written.
Two independently stereogenic substituted phosphates give four combinations: $(R_P,R_P)$, $(R_P,S_P)$, $(S_P,R_P)$ and $(S_P,S_P)$. Their <molecular masses> are the same. A mass measurement alone cannot determine either the configuration at one site or the proportions in an unresolved mixture.
A simple activity model shows why mixture composition can matter. Suppose equal amounts of two purified forms separately give product fractions $0.8$ and $0.2$ in a stipulated assay. If molecules act independently and the assay response is linear, a mixture containing fraction $f$ of the first form gives $p=0.8f+0.2(1-f)$. At $f=1/2$, $p=0.5$. These invented numbers illustrate averaging; competition for limiting components can invalidate that model.
The <U6 metal rescue experiment> supplies an actual chemical distinction. Sulfur substitutions with opposite phosphorus configurations at the same U6 position showed differing metal-rescue behavior, including differences between branching and exon ligation.<RNA catalyses nuclear pre-mRNA splicing by Sebastian M. Fica and others>[Figure2, U80 substitution configurations and separate branching/ligation assays, pp.229–230.]{ref} Position, configuration and measured reaction therefore belong in the description of a phosphorothioate reagent.
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