A kinetic estimate of the free aldehyde content of aldoses

doi:10.1016/S0008-6215(00)00204-4

Carbohydrate Research

Volume 329, Issue 2, 3 November 2000, Pages 359-365

https://doi.org/10.1016/S0008-6215(00)00204-4 Get rights and content

Abstract

The relative free aldehyde content of eight hexoses and four pentoses has been estimated within about 10% from the rate constants for their reaction with urazole (1,2,4-triazole-3,5-dione). These values of the percent free aldehyde are in agreement with those estimated from CD measurements, but are more accurate. The relative free aldehyde contents for the aldoses were then correlated to various literature NMR measurements to obtain the absolute values. This procedure was also done for three deoxyaldoses, which react much more rapidly than can be accounted for by the free aldehyde content. This difference in reactivity between aldoses and deoxyaldoses is due to the inductive effect of the H versus the OH on C-2′. This may help explain why deoxyribonucleosides hydrolyze much more rapidly than ribonucleosides.

Introduction

The free aldehyde content (fraction of free aldehydo form in aqueous solution of an aldose in mutarotational equilibrium) of aldoses is important in understanding aldose reactivity [1], [2] and stability [3]. It may also be related to the choice of glucose as the major hexose in biology, since it has the least free aldehyde and is thus the least reactive hexose with proteins [4]. This choice has been attributed [5] to the all-equatorial hydroxyls of glucose, but this seems unlikely as a dominant factor since the difference in free energy of formation of the various hexoses is small (∼1.2 kcal/mol) [6]. However, the very low free aldehyde content of aldoses is very difficult to measure.

The first accepted measurement for the free aldehyde content of glucose is 0.0026%, which was determined via polarography at 25 °C [7]. However, there is only one survey of relative aldehyde content for the straight chain aldopentoses and aldohexoses. This survey (at 20 °C) used the circular dichroism (CD) of the 290 nm n to π* transition in the carbonyl functional group, calibrated from the optical rotatory dispersion (ORD) of various ketones and aldehydes in methanol, heptane, and chloroform [8], and was confirmed by the agreement of the glucose value with the polaragraphic value. Angyal [9] stated that these values are correct within an order of magnitude and are primarily reliable only on a relative basis. Subsequent measurements of ¹³C-enriched glucose via ¹³C NMR spectroscopy can be extrapolated to 20 °C to give a substantially different value [10]. NMR values for idose, ribose, and talose were also considerably different [1], [11], [12] from those obtained from CD.

In the course of investigating the reactivity of ribose and other aldoses with urazole (1,2,4-triazole-3,5-dione) [13], [14], it became apparent that the rates are approximately proportional to the content of free aldehyde. We have measured these relative values based on kinetics and calibrated the absolute free aldehyde values with several NMR measurements. This is useful as a systematic measurement of the free aldehyde, particularly since the free aldehyde content of most aldoses has not been measured by NMR spectroscopy. We have also measured 2-deoxyribose (i.e., 2-deoxy-d-erythro-pentose) and two of the 2-deoxyhexoses. These results allow us to constrain a model that can explain the rapid acid-catalyzed hydrolysis of deoxynucleosides relative to ribonucleosides. The rapid hydrolysis of purine deoxyribosides is a major source of damage to DNA for which various repair systems are needed [15].

Section snippets

Materials

1-Methylurazole was synthesized by the method of Bausch et al. [16]. Urazole and 4-methylurazole were from Aldrich Chemical Co. Sigma Chemical Co. supplied the glycolaldehyde, paraldehyde, dihydroxyacetone, and all the sugars except for gulose (Biospherics) and glucose (Fisher). All deuterated solvents were from Cambridge Isotope Laboratories. The acetaldehyde (Mallinckrodt) was purified by vacuum distillation from CHCl₃ (l)/CHCl₃ (s) to N₂ (l) to remove any paraldehyde or other contaminants

Results

The reaction of urazole with aldoses gave reversible first-order kinetics [14]. The equilibrium constants K_eq=[UR]/[U][R] varied between 0.5 and 3.1 [14]. Reaction rates with various aldoses were monitored over time at 25 °C except for mannose and glucose, which were obtained by Arrhenius extrapolations from data at 120, 100, 80, and 60 °C. Some of the aldoses were also measured at 100 °C in addition. The reaction was determined to be at the N₁ of the urazole [13], and the rate of ring closure of

Discussion

The kinetic procedure to obtain the relative percent free aldehyde can be justified on the following A₂ reaction mechanism. This has also been proposed for the depyrimidation of 2′-deoxyuridine and thymidine [22] (Scheme 1).

The K_op and K_add are stated as in rapid equilibrium and the k₃ is the slow step

Acknowledgements

We thank Professor Charles Perrin for helpful comments and Michael Robertson and Matthew Levy for helpful comments and technical assistance and the NASA Specialized Center of Research and Training in exobiology for a fellowship (J.P.D.) and grant support (S.L.M.).

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¹: Present address: NASA Ames Research Center, M/C 245-6, Moffett Field, CA 94035-1000, USA.

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A kinetic estimate of the free aldehyde content of aldoses

Abstract

Introduction

Section snippets

Materials

Results

Discussion

Acknowledgements

Adv. Carbohydr. Chem. Biochem.

J. Am. Chem. Soc.

J. Am. Chem. Soc.

Proc. Natl. Acad. Sci. USA

Science

Q. Rev. Biol.

J. Phys. Chem. Ref. Data

J. Am. Chem. Soc.

Carbohydr. Res.

J. Am. Chem. Soc.

J. Org. Chem.

J. Am. Chem. Soc.

J. Mol. Evol.