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Detection of potential TNA and RNA nucleoside precursors in a prebiotic mixture by pure shift diffusion-ordered NMR spectroscopy.

Islam S, Aguilar JA, Powner MW, Nilsson M, Morris GA, Sutherland JD - Chemistry (2013)

Bottom Line: One potential avenue is the combination of pure shift methodology, in which NMR spectra are measured with greatly improved resolution by suppressing multiplet structure, with diffusion-ordered spectroscopy, in which NMR signals from different species are distinguished through their different rates of diffusion.Such a combination has the added advantage of working with intact mixtures, allowing analyses to be carried out without perturbing mixtures in which chemical entities are part of a network of reactions in equilibrium.The direct formation of potential RNA and TNA nucleoside precursors, amongst other adducts, was observed.

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Affiliation: School of Chemistry, University of Manchester, Oxford Road, Manchester, M13 9PL, UK. saidul.islam@qmul.ac.uk

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1H pure shift Oneshot DOSY spectrum obtained with the pulse sequence of Figure 3 b; shaded rectangles are used to highlight particular diffusion ranges. The corresponding spectrum for the aromatic region (δ=6.5–7.5 ppm) is shown in Figure 2. The lack of signals in Band 5 supports the assignment of 5 in Figure 2, whereas the aliphatic signals of 14 are seen in Band 2. Diastereoisomeric tetrose aminooxazolines rac-15 and rac-16 share the same diffusion band as expected. The structures and assignments shown are based on the combined evidence of Figure 2, Figure 4, Figure 5 and of the conventional 2D-NMR experiments (see the Supporting Information).
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fig06: 1H pure shift Oneshot DOSY spectrum obtained with the pulse sequence of Figure 3 b; shaded rectangles are used to highlight particular diffusion ranges. The corresponding spectrum for the aromatic region (δ=6.5–7.5 ppm) is shown in Figure 2. The lack of signals in Band 5 supports the assignment of 5 in Figure 2, whereas the aliphatic signals of 14 are seen in Band 2. Diastereoisomeric tetrose aminooxazolines rac-15 and rac-16 share the same diffusion band as expected. The structures and assignments shown are based on the combined evidence of Figure 2, Figure 4, Figure 5 and of the conventional 2D-NMR experiments (see the Supporting Information).

Mentions: With the aid of the pure shift NMR techniques described already and of conventional multidimensional NMR we were able to establish the presence of comparable amounts of 2-aminooxazole 5, rac-15 and rac-16. The diastereoisomeric nature of rac-15 and rac-16 is supported by the pure shift DOSY data acquired using the pulse sequence shown in Figure 3 b. Figure 6 shows that the two species diffuse at the same rate, suggesting that they are of similar size. The chemistry of this mixture seems to have stalled at various intermediates and by-products in the pathway towards 5 (Scheme 3). This is reflected in the signal distribution of the pure shift DOSY spectrum of Figure 6, in which most of the species appear within a relatively narrow band of diffusion (and hence hydrodynamic radius). As mentioned previously, Cockerill et al. have shown that specific base catalysis improves the reaction yield for 5 to 40 % (Scheme 2).[30] General acid-base catalysis by phosphate is also efficient at pH 7, and results in a clean formation of 5 in>80 % yield.[23] Both types of catalysis presumably facilitate the 5-exo-dig cyclisation of the hydroxyl group onto the nitrile carbon of 10 to give 11, as well as the C–H deprotonation of 17 leading to 3 (Schemes 2 and 3).[23] During the course of the reaction the pD rises to (and levels off at) pD 13. Despite this rise in pD, signals corresponding to potential aldol products were not identifiable, and it is assumed that if such chemistry had taken place, it was at low level. Further sequestration of cyanamide 7 by addition to N-cyano imine 18 to give 19, and the oligomerisation of 7 in aqueous solution (see below), would result in the temporary excess of 6 required for the formation of rac-15 and rac-16. 2-aminooxazole 5 is known to be a good C nucleophile at neutral pH, and reacts cleanly with various aldehydes and imines.[27, 45–47] For example, when isolated 5 is reacted with 6 in unbuffered water at neutral pH, the reaction proceeds in approximately 90 % yield, with a small diastereoselectivity for the kinetically-preferred rac-15 over rac-16 in a 46:43 ratio (Scheme 4).[27] However, the reaction mixture analysed in this pure shift DOSY study shows that rac-16 predominated over rac-15 (rac-15/rac-16, 1:1.7). If 6 and 7 are mixed in a 2:1 ratio, a greater formation of rac-15 and rac-16 is observed, with a slight relative increase in the diastereoselectivity for rac-16 (rac-15/rac-16, 1:1.9), but now complexity between δ=3.4 and 3.8 ppm suggests that aldol chemistry had taken place due to the excess of 6 (with respect to 7) in the reaction (Figure 7).


Detection of potential TNA and RNA nucleoside precursors in a prebiotic mixture by pure shift diffusion-ordered NMR spectroscopy.

Islam S, Aguilar JA, Powner MW, Nilsson M, Morris GA, Sutherland JD - Chemistry (2013)

1H pure shift Oneshot DOSY spectrum obtained with the pulse sequence of Figure 3 b; shaded rectangles are used to highlight particular diffusion ranges. The corresponding spectrum for the aromatic region (δ=6.5–7.5 ppm) is shown in Figure 2. The lack of signals in Band 5 supports the assignment of 5 in Figure 2, whereas the aliphatic signals of 14 are seen in Band 2. Diastereoisomeric tetrose aminooxazolines rac-15 and rac-16 share the same diffusion band as expected. The structures and assignments shown are based on the combined evidence of Figure 2, Figure 4, Figure 5 and of the conventional 2D-NMR experiments (see the Supporting Information).
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3814424&req=5

fig06: 1H pure shift Oneshot DOSY spectrum obtained with the pulse sequence of Figure 3 b; shaded rectangles are used to highlight particular diffusion ranges. The corresponding spectrum for the aromatic region (δ=6.5–7.5 ppm) is shown in Figure 2. The lack of signals in Band 5 supports the assignment of 5 in Figure 2, whereas the aliphatic signals of 14 are seen in Band 2. Diastereoisomeric tetrose aminooxazolines rac-15 and rac-16 share the same diffusion band as expected. The structures and assignments shown are based on the combined evidence of Figure 2, Figure 4, Figure 5 and of the conventional 2D-NMR experiments (see the Supporting Information).
Mentions: With the aid of the pure shift NMR techniques described already and of conventional multidimensional NMR we were able to establish the presence of comparable amounts of 2-aminooxazole 5, rac-15 and rac-16. The diastereoisomeric nature of rac-15 and rac-16 is supported by the pure shift DOSY data acquired using the pulse sequence shown in Figure 3 b. Figure 6 shows that the two species diffuse at the same rate, suggesting that they are of similar size. The chemistry of this mixture seems to have stalled at various intermediates and by-products in the pathway towards 5 (Scheme 3). This is reflected in the signal distribution of the pure shift DOSY spectrum of Figure 6, in which most of the species appear within a relatively narrow band of diffusion (and hence hydrodynamic radius). As mentioned previously, Cockerill et al. have shown that specific base catalysis improves the reaction yield for 5 to 40 % (Scheme 2).[30] General acid-base catalysis by phosphate is also efficient at pH 7, and results in a clean formation of 5 in>80 % yield.[23] Both types of catalysis presumably facilitate the 5-exo-dig cyclisation of the hydroxyl group onto the nitrile carbon of 10 to give 11, as well as the C–H deprotonation of 17 leading to 3 (Schemes 2 and 3).[23] During the course of the reaction the pD rises to (and levels off at) pD 13. Despite this rise in pD, signals corresponding to potential aldol products were not identifiable, and it is assumed that if such chemistry had taken place, it was at low level. Further sequestration of cyanamide 7 by addition to N-cyano imine 18 to give 19, and the oligomerisation of 7 in aqueous solution (see below), would result in the temporary excess of 6 required for the formation of rac-15 and rac-16. 2-aminooxazole 5 is known to be a good C nucleophile at neutral pH, and reacts cleanly with various aldehydes and imines.[27, 45–47] For example, when isolated 5 is reacted with 6 in unbuffered water at neutral pH, the reaction proceeds in approximately 90 % yield, with a small diastereoselectivity for the kinetically-preferred rac-15 over rac-16 in a 46:43 ratio (Scheme 4).[27] However, the reaction mixture analysed in this pure shift DOSY study shows that rac-16 predominated over rac-15 (rac-15/rac-16, 1:1.7). If 6 and 7 are mixed in a 2:1 ratio, a greater formation of rac-15 and rac-16 is observed, with a slight relative increase in the diastereoselectivity for rac-16 (rac-15/rac-16, 1:1.9), but now complexity between δ=3.4 and 3.8 ppm suggests that aldol chemistry had taken place due to the excess of 6 (with respect to 7) in the reaction (Figure 7).

Bottom Line: One potential avenue is the combination of pure shift methodology, in which NMR spectra are measured with greatly improved resolution by suppressing multiplet structure, with diffusion-ordered spectroscopy, in which NMR signals from different species are distinguished through their different rates of diffusion.Such a combination has the added advantage of working with intact mixtures, allowing analyses to be carried out without perturbing mixtures in which chemical entities are part of a network of reactions in equilibrium.The direct formation of potential RNA and TNA nucleoside precursors, amongst other adducts, was observed.

View Article: PubMed Central - PubMed

Affiliation: School of Chemistry, University of Manchester, Oxford Road, Manchester, M13 9PL, UK. saidul.islam@qmul.ac.uk

Show MeSH
Related in: MedlinePlus