Serine undergoes chiroselective self-directed oligomerization to form a singly protonated octamer under positive ion electrospray conditions, as identified by ion trap tandem mass spectrometry. The experiments also show a series of higher-order clusters (metaclusters) corresponding to [(Ser8H)n]n+, n = 1, 2, 3. There is a magic number effect favoring formation of the protonated octamer over its homologues and also a strong preference for octamer formation from homochiral serine molecules. Collision-induced dissociation suggests that the protonated octamer is composed of four hydrogen-bonded dimers, stabilized by further extensive hydrogen bonding. Density functional calculations support this model and show that the protonated homochiral octamer is energetically stabilized relative to its possible fragments (dimer plus protonated hexamer, etc). The calculations also show that heterochiral octamers are less stable than homochiral octamers (e.g., the protonated 7:1 cluster is 2.1 kcal/mol less stable than the 8:0 analogue). The implications of these results for the origin of homochirality are discussed.

Self-clustering of the five common nucleobases was investigated by electrospray ionization tandem mass spectrometry and shown to provide insight into the non-covalent interactions between identical bases. Alkali and ammonium cations significantly increase self-aggregation of the nucleobases and lead to the formation of uniquely stable magic number clusters. Sodium adducts of guanine, thymine and uracil preferentially take the form of tetrameric (quartet) clusters. This gas-phase result correlates with previously reported solution-phase data on sodium cation stabilized guanosine, thymine and uracil quartet structures believed to be responsible for telomere stabilization. In the presence of potassium, cesium or ammonium cations, pentameric magic number clusters are formed from thymine and uracil, while in solution the nucleoside isoguanosine yields clusters of this favored size. The formation of magic number metaclusters occurs for thymine and uracil in the presence of ammonium cations. These doubly charged 10- and 15-mers are tentatively attributed to the formation of pentamer/ammonium cation/ pentamer sandwich structures.

Electrospray ionization (ESI) mass spectra of nucleosides, recorded in the presence of alkali metals, display alkali metal ion-bound quartets and other clusters that may have implications for understanding non-covalent interactions in DNA and RNA. The tetramers of guanosine and deoxyguanosine and also their metaclusters (clusters of clusters), cationized by alkali metals, were observed as unusually abundant magic number clusters. The observation of these species in the gas phase parallels previous condensed-phase studies, which show that guanine derivatives can form quartets and metaclusters of quartets in solution in the presence of metal cations. This parallel behavior and also internal evidence suggest that bonding in the guanosine tetramers involves the bases rather than the sugar units. The nucleobases thymine and uracil are known to form magic number pentameric adducts with K+, Cs+ and NH4+ in the gas phase. In sharp contrast, we now show that the nucleosides uridine and deoxythymidine do not form the pentameric clusters characteristic of the corresponding bases. More subtle effects of the sugars are evident in the fact that adenosine and cytidine form numerous higher order clusters with alkali metals, whereas deoxyadenosine and deoxycytidine show no clustering. It is suggested that hydrogen bonding between the bases in the tetramers of dG and rG are the dominant interactions in the clusters, hence changing the ribose group to deoxyribose (and vice versa) generally has little effect. However, the additional hydroxyl group of RNA nucleosides enhances the non-selective formation of higher-order aggregates for adenosine and cytidine and results in the lack of highly stable magic number clusters. Some clusters are the result of aggregation in the course of ionization (ESI) whereas others appear to be intrinsic to the solution being examined.

Chiral exchange: Substitution of cysteine for serine in the homochiral serine octamer (see calculated structure) occurs in a chirally dependent fashion and may represent an example of transfer of chirality between primitive biological molecules. The findings are supported by HF/6‐31G calculations.

Some α-amino acids, especially arginine, form protonated clusters when examined by electrospray ionization in an ion trap mass spectrometer. Singly-, doubly-, triply-and quadruply-protonated arginine clusters [(Arg) n + H] + , [(Arg) m + 2H] +2 , [(Arg) l + 3H] +3 and [(Arg) k + 4H] +4 , were further studied by collision-induced dissociation (CID). The singly-protonated cluster n = 4 displayed enhanced stability and CID of larger clusters (n > 4) showed fragmentation leading to the preferential formation of n = 4 product ions. The n = 4 stable cluster is proposed to bear a formal resemblance to the simple salt cluster [(NaCl) 4 + Na] + , a 3 × 3 × 1 micro-crystallite. This leads to the suggestion that [(Arg) 4 + H] + is planar, with bonding primarily due to the electrostatic interactions between four zwitterionic arginine molecules. In the doubly-charged ion series, clusters of m = 12-15 have enhanced stability relative to those of immediately smaller size. Drawing on the analogous salt structures, the dication, [(Arg) 12 + 2H] +2 might have a structure consisting of three layers of tetramers, two of which are protonated. This structure is analogous to that of the magic number doubly-charged ionic cluster [(NaCl) 12 + 2Na] +2 which is a 3 × 3 × 3 micro-crystallite with an internal anion defect.