Microwave Spectroscopy DOI: 10.1002/ange.201305589 Six Pyranoside Forms of Free 2-Deoxy-d-ribose** Isabel PeÇa, Emilio J. Cocinero,* Carlos Cabezas, Alberto Lesarri, Santiago Mata, Patricia Écija, Adam M. Daly, lvaro Cimas, Celina Bermffldez, Francisco J. Basterretxea, Susana Blanco, JosØ A. Fernµndez, Juan C. López, Fernando CastaÇo, and JosØ L. Alonso* Carbohydrates are one of the most versatile biochemical building blocks, widely acting in energetic, structural, or recognition processes. [1] The interpretation of the biological activity of saccharides is based on the structure and relative stability of their conformers. One of the obstacles to resolving the basic structure issues arises from their ability to form strong intermolecular hydrogen bonds with polar solvents, which in turn can result in conformational changes. A clear picture of the conformational panorama of isolated 2-deoxy- d-ribose has been revealed using Fourier-transform micro- wave spectroscopy in conjunction with a UV ultrafast laser ablation source. Additionally, the availability of rotational data has been the main bottle-neck for examining the presence of these building blocks in interstellar space, [2] so these studies could also be useful to the astrochemistry community. 2-Deoxy-d-ribose (2DR, C 5 H 10 O 4 ; Figure 1 a) is an impor- tant naturally occurring monosaccharide, present in nucleo- tides, which are the building blocks for DNA. [3] In DNA, 2DR is present in the furanose (five-membered) ring form, whereas free in aqueous solution it cyclizes into five- or six-membered rings, with the latter—the pyranoid form—being dominant. [4] By closing the chain into a six-membered ring, the C 1 carbon atom is converted into an asymmetric center, yielding two possible stereochemical a and b anomeric species (Fig- ure 1 b). In aqueous solution, 2DR primarily exists as a mixture of nearly equal amounts of a and b pyranose forms, present in their low-energy chair conformations, 4 C 1 and 1 C 4 (Figure 1 c). [4] Such configurations are connected through ring inversion, thus establishing the axial or equato- rial position of the OH group for each conformer. In addition, the monossacharides exhibit an unusual preferential stabili- zation of pyranose rings containing an axial OH group at the C 1 carbon over the equatorial orientation, widely known as the anomeric effect, [5] although its physical origin remains controversial. [6] Nevertheless, structural analysis of 2DR must take into consideration the intramolecular hydrogen bonding between adjacent OH groups. The formation of hydrogen- bond networks reinforces their stability owing to hydrogen- bond cooperativity effects. [7] Such networks are fundamental to the molecular recognition of carbohydrates. [8] By dissecting all these factors we can determine the most stable conformers of 2DR and the relative arrangement of the different hydroxy groups under isolated conditions, such as in the gas phase. In vacuo theoretical calculations, carried out on a-/b- pyranoses, a-/b-furanoses, and open-chain conformations, predict 15 furanose and pyranose forms (Figure 1d, Table 1) in an energy window of 12 kJ mol À1 above the predicted cc-a- pyr 4 C 1 global minimum. The notation used to label the different conformers include the symbols a and b to denote the anomer type, 4 C 1 and 1 C 4 to denote the pyranose chair form, C2-endo or C3-endo to denote the furanose envelope forms, and “c” or “cc” to indicate a clockwise or counter- clockwise configuration of the adjacent OH bonds, respec- tively. A number is added to provide the MP2 energy ordering within the same family. To validate the predicted conforma- tional behavior, comparison with precise experimental data of 2DR is needed. Previous experiments to determine the conformation of monosaccharides were based on X-ray and NMR measurements. [9, 4] However, these data are influenced by environmental effects associated with the solvent or crystal lattice. Recently, an IR spectrum of 2DR in an inert matrix in [*] Dr. I. PeÇa, Dr. C. Cabezas, S. Mata, Dr. A.M. Daly, C. Bermffldez, Dr. S. Blanco, Prof. J. C. López, Prof. J. L. Alonso Grupo de Espectroscopia Molecular (GEM), Unidad Asociada CSIC Edificio Quifima, Laboratorios de Espectroscopia y Bioespectrosco- pia, Parque Científico UVa, Universidad de Valladolid 47005 Valladolid (Spain) E-mail: jlalonso@qf.uva.es Homepage: http://www.gem.uva.es Dr. E. J. Cocinero, Dr. P. Écija, Dr. F. J. Basterretxea, Dr. J. A. Fernµndez, Prof. F. CastaÇo Departamento de Química Física, Facultad de Ciencia y Tecnología Universidad del País Vasco (UPV-EHU) Apartado 644, 48080 Bilbao (Spain) E-mail: emiliojose.cocinero@ehu.es Homepage: http://www.grupodeespectroscopia.es/MW Prof. A. Lesarri Departamento de Química Física y Química Inorgµnica Facultad de Ciencias, Universidad de Valladolid 47011 Valladolid (Spain) Dr. . Cimas Laboratoire Analyse et ModØlisation pour la Biologie et l’Environnement, UniversitØ d’Évry val d’Essonne 91025 Evry (France) [**] This research was supported by the MICINN and MINECO (Grants CTQ 2006-05981/BQU, CTQ 2010-19008, CTQ2011-22923, CTQ2012-39132 and Consolider Ingenio 2010 CSD 2009-00038 and 2010/CSD2007-00013), Junta de Castilla y León (Grant VA070A08), the Basque Government (Consolidated Groups, IT520-10) and the UPV/EHU (UFI11/23). C.B. thanks the MICINN for a FPI grant (BES-2011-047695). E.J.C. acknowledges also a “Ramón y Cajal” contract. Computational resources and laser facilities of the UPV/ EHU were used in this work (SGIker and I2Basque). Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/anie.201305589. A ngewandte Chemi e 1 Angew. Chem. 2013, 125,1–7  2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim These are not the final page numbers! Ü Ü