title: DFT/PCM theoretical study of the conversion of methyl 4-O-methyl-α-d-galactopyranoside 6-sulfate and its 2-sulfated derivative into their 3,6-anhydro counterparts.
abstract: Modeling of the conversion of methyl 4-O-methyl-α-d-galactopyranoside 6-sulfate (2) and 2,6-disulfate (1) into methyl 3,6-anhydro-4-O-methyl-α-d-galactopyranoside (4) and its 2-sulfate (3), respectively (Scheme 1) has been carried out using DFT at the M06-2X/6-311 + G(d,p)//M06-2X/6-31 + G(d,p) level with the polarizable continuum model (PCM) in water. The three steps necessary for the alkaline transformation of 6-sulfated (and 2,6-disulfated) galactose units into 3,6-anhydro derivatives were evaluated. The final substitution step appears to be the rate limiting, involving an activation energy of ca. 23 kcal/mol. The other two steps (deprotonation and chair inversion) combined involve lower activation energies (9-12 kcal/mol). Comparison of the thermodynamics and kinetics of the reactions suggest that if the deprotonation step precedes the chair inversion, the reaction should be faster for both compounds. No major differences in reaction rate can be theoretically predicted to be caused by the presence of sulfate on O-2, although one experimental result suggested that O-2 sulfation should increase the reaction rate. The conformational pathways are complex, given the large number of rotamers available for each compound, and the way that some of these rotamers combine into some of the pathways. In any case, the conformation (O)S2 appears as a common intermediate for the chair inversion processes.
authors.affiliation: Departamento de Química Orgánica-CIHIDECAR, FCEyN-Universidad de Buenos Aires, Ciudad Universitaria, Buenos Aires 1428, Argentina.
authors.forename: Vanina A
authors.initials: VA
authors.lastname: Cosenza
authors.affiliation: Departamento de Química Orgánica-CIHIDECAR, FCEyN-Universidad de Buenos Aires, Ciudad Universitaria, Buenos Aires 1428, Argentina.
authors.forename: Diego A
authors.initials: DA
authors.lastname: Navarro
authors.affiliation: Departamento de Química Orgánica-CIHIDECAR, FCEyN-Universidad de Buenos Aires, Ciudad Universitaria, Buenos Aires 1428, Argentina. Electronic address: stortz@qo.fcen.uba.ar.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Stortz
mesh_terms: D002236:Carbohydrate Conformation; D009005:Monosaccharides / Q000737:chemistry*; D011789:Quantum Theory; D013431:Sulfates / Q000737:chemistry*
chemical_list: C000613145:4-O-methyl-alpha-D-galactopyranoside 6-sulfate; D009005:Monosaccharides; D013431:Sulfates
keywords: 3,6-Anhydrogalactose; Alkaline treatment; Carrageenans; Conformation; Density functional theory; Galactose 6-sulfate