On Serine Octamer Substitution Reactions

ABSTRACT Rationale Monomeric amino acids substitute into the ionized serine octamer (Ser 8 ), a magic number cluster that exhibits chiral behavior. Small biomolecules, such as amino acids (AA), substitute into the octamer enantioselectively, giving Ser 7 AAH + and Ser 6 AA 2 H + favoring clusters of all L‐ or all D‐chirality. While the formation of Ser 8 H + has been well studied, its substitution reactions need further investigation. The fact that water microdroplets readily produce Ser 8 H + , which undergoes enantiospecific substitution reactions perhaps gives this topic relevance to origins of life chemistry. Methods The substitution reactions of several proteogenic AA's (Ala, Leu, isoLeu, Pro, Phe, and Val), along with prebiotically relevant isomers (norVal and isoVal), were investigated using a quadrupole ion trap mass spectrometer to gain insight into the determinants of the chiral behavior. Rather than using isotopically labeled enantiomers, as in previous work, cluster formation was assessed using samples of variable chiral composition and concentration. Results Substitution enantioselectivity was confirmed, though in the case of some double substitutions and the substitution of nonproteogenic isomers, the homochiral preference was decreased or inverted, an observation which is attributed to the disruption of the highly ordered noncovalent contacts of the parent Ser 8 cluster. Additionally, the data suggest that octamer formation is consecutive: Ser 8 H + forms first, followed by substitution of AA to form Ser 7 AAH + , sometimes followed by a second substitution to form Ser 6 AA 2 H + . Conclusions This investigation illustrates how chiral chemistry using MS must operate through weak but chirality‐sensitive forces while avoiding dominance of stronger but chirality‐insensitive reaction drivers; namely the propensity of a chiral organic base to acquire the charge of a proton affiliated with other chiral molecules. These results are significant because chiral molecular clusters are fundamentally interesting. Understanding the origins of their enantioselectivity contributes to a general understanding of how small molecules may recognize chirality in reaction partners and accumulate enantiomeric excess.