Durch Molybdationen katalysierte Reaktionen bei Kohlenhydraten, VIII Epimerisierung von D‐Galactose

A reoptimized GROMOS force field for hexopyranose‐based carbohydrates accounting for the relative free energies of ring conformers, anomers, epimers, hydroxymethyl rotamers, and glycosidic linkage conformers

“…1) associated with the C 2 ‐epimerization equilibrium (based on population ratios determined under metal‐catalyzed reaction conditions, see ref 21. and references therein125–131). Focusing on studies where the obtension of an equilibrium C 2 ‐epimer mixture was assessed, the Δ G 2eq→2ax values for the All → Alt, Glc → Man, and Gal → Tal epimerization processes in water are estimated to be125, 126, 128, 129, 131 1.2, 2.3–2.7, and 3.0 − 3.6 kJ mol −1 , respectively.…”

“…The corresponding modified parameter set will be further referred to here as 45A4 ASPG . Because the corresponding data was not taken into account during the parameterization,73 the 45A4 force field is also not likely to reproduce accurately the relative free energies of the α‐ and β‐anomers of hexopyranoses (experimentally accessible124) as well as the relative free energies of exocyclic group epimers (sometimes also experimentally accessible, see ref 21. and references therein125–131). The free lactol group of β‐ D ‐hexopyranoses in water presented a conformational distribution in apparent disagreement with the exo ‐anomeric effect 21.…”

“…The thermodynamics of anomerization and epimerization processes is often of high practical relevance, in the context of e.g. : (i) anomeric equilibria of unfunctionalized hexopyranoses124 (ratio of α‐ to β‐anomer); (ii) metal‐catalyzed epimerization equilibria of unfunctionalized hexopyranoses125, 126, 181; (iii) enzymatic epimerization of polysaccharides182–185; and (iv) intermediates in glycosylation reactions95, 186–188 (ratio of α‐ to β‐linked products). Although the interconversion between the α‐ and β‐anomer of a free lactol group is a complex long‐timescale process (mutarotation via ring opening and closing, on the 10 3 s timescale145, 189–195), one could envision simulation approaches accelerating this process along an unphysical pathway (improper dihedral inversion), so as to reach appropriate equilibrium populations of the two anomers on the simulation timescale.…”

“…The thermodynamics of anomerization and epimerization processes is often of high practical relevance, in the context of e.g. : (i) anomeric equilibria of unfunctionalized hexopyranoses124 (ratio of α‐ to β‐anomer); (ii) metal‐catalyzed epimerization equilibria of unfunctionalized hexopyranoses125, 126, 181; (iii) enzymatic epimerization of polysaccharides182–185; and (iv) intermediates in glycosylation reactions95, 186–188 (ratio of α‐ to β‐linked products).…”

“…These processes include: (i) ring conformational transitions in aqueous hexopyranoses, with timescales of the order of21, 92, 103 0.05−1 μs (NMR140, 141 and ultrasonic relaxation142–145 experiments) or 0.02−1 μs (estimated using the 45A4 force field92) depending on the considered compound and type of transition; (ii) rotations around the glycosidic dihedral angles ϕ and ψ in aqueous disaccharides, with timescales of the order of103 0.01−0.02 μs (ultrasonic relaxation experiments144, 145, 196–198) or 0.05−2 μs (estimated using the 45A4 force field99, 100, 103) depending on the considered compound; and (iii) anomerization or epimerization transitions, experimentally slow for the former (timescale of the order of 10 3 s via ring opening and closing145, 189–195) and the latter in the absence of catalyst (see ref 21. and references therein125–131), and both typically unphysical within a classical force‐field description (sign inversion in the reference value for an improper dihedral angle). The rotational dynamics of the other relevant degrees of freedom are comparatively faster, namely ∼30 ps (hydroxyl groups21, 99, 100) and ∼1 ns (free lactol group,21, 99, 100 free hydroxymethyl groups,21, 99, 100 and glycosidic dihedral angle ω in (1 → 6)‐linked disaccharides99, 100, 103), as estimated using the GROMOS 45A4 force field (or from ultrasonic relaxation142, 145, 199 and NMR140, 200, 201 experiments for the hydroxymethyl group rotation).…”