Interactions of Amino Acids and Aminoxazole Derivatives: Cocrystal Formation and Prebiotic Implications Enabled by Computational Analysis
In line with the postulated intermediacy of aminoxazoles derived from small sugars toward the direct assembly of nucleoside precursors, we show here a potential prebiotic scenario where aminoxazolines might have also played further roles as complexing and/or sequestering agents of other primeval blocks, namely amino acids. To this end, a bis-aminoxazoline derivative, generated from dihydroxyacetone and cyanamide, gives rise to stable co-crystal forms with dicarboxylic amino acids (Asp and Glu), while ionic interactions owing to proton transfer are inferred from spectroscopic data in aqueous solution. The structure of a 1:2 aminoxazoline: aspartic acid complex, discussed in detail, was elucidated by X-ray diffractometry. Optimized geometries of such ionic structures with bulk aqueous solvation were assessed by DFT calculations, which disclose preferential arrangements that validate the experimental data. Peripherally, we were able to detect in a few cases amino acid dimerization (i.e. dipeptide formation) after prolonged incubation with the bis-aminoxazole derivative. A mechanistic simulation aided by computation provides some predictive conclusions for future explorations and catalytic design.
KeywordsPrebiotic chemistry Amino acids Aminoxazole chemistry Reaction mechanism Dipeptide
This work was supported by Junta de Extremadura and Fondo Europeo de Desarrollo Regional (Grants IB16167 and GR18015). We also gratefully acknowledge the Cénits/COMPUTAEX Foundation for providing computing time on the LUSITANIA Supercomputer.
- Budin I, Szostak JW (2010) Expanding roles for diverse physical phenomena during the origin of life. Annu Rev Biophys 39:245–263. https://doi.org/10.1146/annurev.biophys.050708.133753 CrossRefPubMedPubMedCentralGoogle Scholar
- Das B, Srivastava HK (2017) Influence of the local chemical environment in the formation of multicomponent crystals of L-tryptophan with N-heterocyclic carboxylic acids: unusual formation of double zwitterions. Cryst Growth Des 17:3796–3805. https://doi.org/10.1021/acs.cgd.7b00386 CrossRefGoogle Scholar
- Ditchfield R, Hehre WJ, Pople JA (1971) Self-consistent molecular-orbital methods. IX. An extended Gaussian-type basis for molecular-orbital studies of organic molecules. J Chem Phys 54:724–728. https://doi.org/10.1063/1.1674902
- Frisch MJ, Trucks GW, Schlegel HB et al. (2009) Gaussian 09. Revision D.01. Gaussian, Inc, Wallingford, CT, USAGoogle Scholar
- Grouiller A, Mackenzie G, Najib B, Shaw G, Ewing D (1988) A novel stereospecific synthesis of 5-amino-1-β-D-fructofuranosylimidazole-4-carboxamide. J Chem Soc Chem Commun:671–672. https://doi.org/10.1039/C39880000671
- Hall SR, McMahon B (2006) International tables for crystallography vol G: definition and exchange of crystallographic data. International union of crystallography. Wiley, New YorkGoogle Scholar
- Marenich AV, Cramer CJ, Truhlar DG (2009a) Universal solvation model based on solute electron density and on a continuum model of the solvent defined by the bulk dielectric constant and atomic surface tensions. J Phys Chem B 113:4538–4543. https://doi.org/10.1021/jp810292n CrossRefPubMedGoogle Scholar
- Müller D, Pitsch S, Kittaka A, Wagner E, Wintner CE, Eschenmoser A, Ohlofjgewidmet G (1990) Chemie von α-aminonitrilen. Aldomerisierung von glycolaldehyd-phosphat zu racemischen hexose-2,4,6-triphosphaten und (in gegenwart von formaldehyd) racemischen pentose-2,4-diphosphaten: rac-allose-2,4,6-triphosphat und rac-ribose-2,4-diphosphat sind die reaktionshauptprodukte. Helv Chim Acta 73:1410–1468. https://doi.org/10.1002/hlca.19900730526 CrossRefGoogle Scholar
- Saul R, Kern T, Kopf J, Pintér I, Köll P (2000) Reaction of 1,3-disubstituted acetone derivatives with pseudohalides: a simple approach to spiro[4.4]nonane-type bis-oxazolidines and -imidazolidines (bicyclic carbamates, thiocarbamates, ureas, and thioureas). Eur J Org Chem:205–209Google Scholar
- Zhao Y, Truhlar DG (2008) The M06 suite of density functionals for main group thermochemistry, thermochemical kinetics, noncovalent interactions, excited states, and transition elements: two new functionals and systematic testing of four M06-class functionals and 12 other function. Theor Chem Accounts 120:215–241. https://doi.org/10.1007/s00214-007-0310-x CrossRefGoogle Scholar