Serine octamer

One may use the stronger term chirality discrimination when a substantial suppression of one intermolecular diastereomer with respect to the other occurs. This requires multiple strong interactions between the two molecular units and therefore more than simple monofunctional alcohols. Some examples where one of the molecules involved is a chiral alkanol are reported in Refs. 112 and 119 121. Pronounced cases of higher-order chirality discrimination have been observed in clusters of hydroxy esters such as methyl lactate tetramers [122] and in protonated serine octamers [15,123,124]. The presence of an alcohol functionality appears to be favorable for accentuated chirality discrimination phenomena even in these complex systems [113,123,125,126]. Because the border between chirality recognition and discrimination is quite undefined, it is suggested that the two may be used synonymously whenever both molecular partners are permanently chiral [127]. 

U. Mazurek, Some more aspects of formation and stability of the protonated serine octamer cluster. Eur. J. Mass Spectrom. 12, 63 70 (2006). 

As for arginine, ESTMS analysis of serine solutions reveals an unusually abundant protonated serine octamers [(Ser)g-nH] " (n= 1-3), which demonstrate a... 

Fig. 16 Calculated HF/6-31G structure (two views) of the protonated serine octamer left, side view right, top-down view (reproduced by permission of the American Chemical Society).

Fig. 17 (a) Calculated position of Na" " near one face of the serine octamer (b) calculated... 

Differently from serine, ESI-MS analysis of homoserine (HSer) solutions reveals an unusually abundant diprotonated homoserine octamers [(HSer)g-2H], but not the expected monoprotonated [(HSer)g H]" one." A 3/1 mixture of L-serine and L-homoserine yields abundant mixed serine octamers with the incorporation of one or two homoserine molecules into the cluster. CID of the isolated [(Ser)6(HSer)2-H] cluster leads to the preferentially loss of two neutral serine molecules. Homoserine is always retained. The ESl-MS spectral patterns of threonine and allothreonine solutions is similar to that of homoserine. A 1/1 mixture of D-serine and D-threonine yields abundant mixed singly- and doubly-charged octamers incorporating from 2 to 6 threonine molecules. Their relative abundance indicates that threonine may incorporate freely into serine clusters because the additional methyl group does not interfere with the bonding of the cluster. 

The enantioselective incorporation of these amino acids into the serine octamers represents an example of chiral transmission to elementary biomolecules and a possible way of chirality amplification on primitive earth. 

Takats, Z. Nanita, S. C. Schlosser, G. Vekey, K. Cooks, R. G. Atmospheric Pressure Gas-Phase H/D Exchange of Serine Octamers. Anal. Chem. 2003b, 75, 6147-6154. 

Schalley and Weis [98] revised the results obtained by several studies on hydrogen bonded serine dimers. Those have reported the formation of unusually stable protonated serine octamers, with a clear preference for homochirality [99-103]. Mixed l- and D-serine clusters show up in a small ratio vs. the homochiral ones. 

The protonated serine octamer (Ser)8H+ is exceptionally stable, with a magic number effect of more than 20. The magic number effect M can be obtained from the mass spectra, by the abundance ratio of the n unit cluster compared with the n 1 and n+1 unit cluster, by the relationship M=2In/(In 1+In+1). Electrospray mass ionization experiments [98], performed on 0.1 M solutions of L-serine and d-[[13]C] Serine, show a strong preference toward the formation of homochiral protonated clusters (L-Ser)8H+ and (D-[13C]Ser)8H + instead of the heterochiral analogs (L-Ser)n (D-[13C]Ser)8 — nH+ (n 1 7). The same trends are obtained in deuterium-labeling... 

The authors performed DFT/BP86 calculations on the serine monomer and octamer. According to their calculations, the zwitterionic serine monomer is less stable than the neutral species by 128 kJ mol-1. For eight serine molecules, this means a destabilization of 1,024 kJ mol-1. However, calculations show the zwitterionic serine octamer is 1,018 kJ mol-1 more stable than eight isolated neutral serine molecules, which is a result of the stabilization by solvation of charges in the cluster. 

Fig. 3.6 Electrostatic interactions in serine octamer between zwitterionic-aminoacid units keep the cluster together...

R.R. Julian et al., Nanocrystalline aggregation of serine detected by electrospray ionization mass spectrometry Origin of the stable homochiral gas-phase serine octamer. J. Phys. Chem. B 106, 1219-1228 (2002)... 

K.J. Koch et al., Serine octamer metaclusters Formation, structure elucidation and implications for homochiral polymerization. Chem. Commun. 18, 1854—1855 (2001)... 

K.J. Koch et al., Chiral transmission between amino acids Chirally selective amino acid substitution in the serine octamer as a possible step in homochirogenesis. Angew. Chem. Int. 

Fig. 5.19. A serine octamer cluster built from zwitterionic L-serine molecules. Left Space filling representation Right favorable interactions (electrostatic attraction, hydrogen bonds) holding the cluster together. Bottom View showing a cyclic array of hydrogen bonds connecting the serines OH groups with carboxylates from adjacent serines. Changing the stereochemistry of only one serine will disconnect this array and thus destabilize heterochiral forms.

Souza, G.H.M.F. Uria, D. Eberlin, M.N. Ion mobility of serine octamer clusters using tri-wave high-definition mass spectrometry. Proc. 56th ASMS Conference on Mass Spectrometry and Allied Topics, Denver, CO, June 1-5, 2008, ThP 042. 

These methods have most often been utilized to investigate the chiral recognition of biorelevant molecules such as amino acids and amino acid esters. Chiral crown ethers as well as cyclodextrins and amino acid metal complexes have been used in a number of studies. " To illustrate the ability of MS to analyze chiral recognition, we focus now on the serine octamer. ... 

Figure 5 Differences between the experimental and the statistically expected intensities of different serine octamers. Note that the factors are shown. This means that the aU-D cluster is 15 times more abundant than expected, whUe the signal for the 4d 4l cluster is five times less intense than calculated from statistics. (Reproduced from Ref. 6. John WUey Sons, Inc., 2009.)...

To gather more detailed information on the serine octamer structure, ion mobility experiments (Box 4) were performed, which showed the cluster to be very com-pact. The experimental collision cross-section was determined in two separate experiments to be in the range of 187-191A. All non-zwitterionic serine octamer structures are calculated to have significantly larger theoretical cross-sections. Consequently, this experiment clearly indicates the serine octamer to contain zwitterionic serines. The additional electrostatic attraction between oppositely charged sites results in the quite compact size. A structure that is in line with these results is shown in Figure 7. 

Box 4 Ion Mobility Experiments An Approach to the Serine Octamer Structure... 

Procedure Generate serine octamer ions in the ESI ion source mass-select ion of interest -> inject package of ions into the drift tube detect ions exiting the drift tube and record their arrival time distribution calculate collision cross-section compare experimental cross-section with theoretical ones calculated for putative structures. 

Figure 7 A possible flattened-cube structure for an all-zwitterionic serine octamer. (a) Front view, (b) Side view of the carboxylate-ammonium salt bridges between different serine molecules. Attractive electrostatic forces between car-boxylates and ammonium groups are marked with arrows, (c) Top view showing the regular pattern of the CH2OH side chains which mediates chiral recognition. Dotted lines indicate serine-carboxylate hydrogen bonds connecting the four top serines. A similar arrangement is realized for the other four series. This structure represents the unprotonated cluster. CH3 refers to the position of the methyl groups of threonine and show them to be located in a sterically nonobstructed position. (Reproduced from Ref. 41. Elsevier, 2002.)...

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