Insights in Homochiral Metal-Organic Frameworks: From Their Synthesis to Enantioselective Applications

A través de la reacció d'un derivat d'aminoàcid i Cu(II) s'ha obtingut la xarxa metaloorgànica (MOF) quiral anomenada TAMOF-1. Per tal de ser utilitzada en la investigació de processos enantioselectius, la síntesi del TAMOF-1 s'ha optimitzat en termes de mida de partícula i superfície porosa, donat que aquests paràmetres són crucials de cara a la seva aplicabilitat. La porositat d'aquest material ens ha permès utilitzar-ho com a catalitzador heterogeni per a processos de resolució cinètica, i com a rebliment de columnes cromatogràfiques per a separacions quirals en fase líquida, tant en columnes cromatogràfiques preparatives, com en columnes analítiques i semipreparatives en HPLC. De fet, s'ha aconseguit separar mescles de regioisòmers no quirals difícils de separar industrialment amb aquestes mateixes columnes, que tenen una vida útil de més de dos anys. Amb l'objectiu d'obtenir anàlegs de TAMOF-1, s'han dissenyat i sintetitzat nous lligands derivats d'aminoàcids anàlegs al lligand original, però amb distàncies més grans entre els grups coordinants. Posteriorment, aquests lligands s'han utilitzat en l'estudi de la formació de nous MOFs quirals, i les estructures obtingudes s'han caracteritzat per raigs X, difracció de pols i adsorció/desorció de nitrogen, entre d'altres tècniques.A través de la reacción de un derivado de aminoácido y Cu(II) se ha obtenido la red metaloorgánica (MOF) quiral llamada TAMOF-1. Con el fin de ser utilizada en la investigación de procesos enantioselectivos, la síntesis de TAMOF-1 se ha optimizado en términos de tamaño de partícula y superficie porosa, ya que estos parámetros son cruciales para controlar su aplicabilidad. La porosidad de este material nos ha permitido utilizarlo como catalizador heterogéneo para procesos de resolución cinética, y como relleno de columnas cromatográficas para separaciones quirales en fase líquida, tanto en columnas cromatográficas preparativas, como en columnas analíticas y semipreparativas en HPLC. De hecho, se ha logrado separar mezclas de regioisómeros no quirales difíciles de separar industrialmente con estas mismas columnas, que tienen una vida útil de más de dos años. Con el objetivo de obtener análogos de TAMOF-1, se han diseñado y sintetizado nuevos ligandos derivados de aminoácidos análogos al ligando original, pero con mayores distancias entre los grupos coordinantes. Posteriormente, estos ligandos se han utilizado para estudiar la formación de nuevos MOFs quirales, y las estructuras obtenidas se han caracterizado por rayos X, difracción de polvo y adsorción/desorción de nitrógeno, entre otras técnicas.Through the reaction of an amino acid derivative and Cu(II), the chiral metal-organic framework (MOF) called TAMOF-1 was obtained. In order to be used in the investigation of enantioselective processes, the synthesis of TAMOF-1 was optimised in terms of particle size and the porous surface, as these parameters are crucial to controlling its applicability. The porosity of this material has allowed us to use it as a heterogeneous catalyst for kinetic resolution processes, and as a stationary phase for chromatographic columns for chiral separation in liquid phase, both in preparative chromatographic columns and in analytical and semi-preparative HPLC columns. In fact, it has been possible to separate mixtures of achiral regioisomers that are difficult to separate industrially with these same columns, which have a lifespan of more than two years. To obtain analogues of TAMOF-1, new ligands derived from amino acids analogous to the original ligand but with greater distances between the coordinating groups have been designed and synthesised. Subsequently, these ligands have been used to study the formation of new chiral MOFs, and the structures obtained have been characterised by single crystal and powder X-ray diffraction and nitrogen adsorption/desorption, among other techniques

Homochiral Metal-Organic Frameworks for Enantioselective Separations in Liquid Chromatography

Selective separation of enantiomers is a substantial challenge for the pharmaceutical industry. Chromatography on chiral stationary phases is the standard method, but at a very high cost for industrial-scale purification owing to the high cost of the chiral stationary phases. Typically, these materials are poorly robust, expensive to manufacture and often too specific for a single desired substrate, lacking desirable versatility across different chiral analytes. Here we disclose a porous, robust homochiral metal-organic framework (MOF), TAMOF-1, built from copper(II) and an affordable linker prepared from natural L-histidine. TAMOF-1 has shown to be able to separate a variety of model racemic mixtures, including drugs, in a wide range of solvents of different polarity, outperforming several commercial chiral columns for HPLC separations. Although not exploited in the present article, it is worthy to mention that the preparation of this new material is scalable to the multikilogram scale, opening unprecedented possibilities for low-energy chiral separation at the industrial scale

TAMOF-1 as a Versatile and Predictable Chiral Stationary Phase for the Resolution of Racemic Mixtures

Metal-organic frameworks (MOFs) have become promising materials for multiple applications due to their controlled dimensionality and tunable properties. The incorporation of chirality into their frameworks opens new strategies for chiral separation, a key technology in the pharmaceutical industry as each enantiomer of a racemic drug must be isolated. Here, we describe the use of a combination of computational modeling and experiments to demonstrate that high-performance liquid chromatography (HPLC) columns packed with TAMOF-1 as the chiral stationary phase are efficient, versatile, robust, and reusable with a wide array of mobile phases (polar and non-polar). As proof of concept, in this article, we report the resolution with TAMOF-1 HPLC columns of nine racemic mixtures with different molecular sizes, geometries, and functional groups. Initial in silico studies allowed us to predict plausible separations in chiral compounds from different families, including terpenes, calcium channel blockers, or P-stereogenic compounds. The experimental data confirmed the validity of the models and the robust performance of TAMOF-1 columns. The added value of in silico screening is an unprecedented achievement in chiral chromatography.</p

CCDC 1898969: Experimental Crystal Structure Determination

Related Article: M. Nieves Corella-Ochoa, Jesús B. Tapia, Heather N. Rubin, Vanesa Lillo, Jesús González-Cobos, José Luis Núñez-Rico, Salvador R.G. Balestra, Neyvis Almora-Barrios, Marina Lledós, Arnau Güell-Bara, Juanjo Cabezas-Giménez, Eduardo C. Escudero-Adán, Anton Vidal-Ferran, Sofía Calero, Melissa Reynolds, Carlos Martí-Gastaldo, José Ramón Galán-Mascarós|2019|J.Am.Chem.Soc.|141|14306|doi:10.1021/jacs.9b0650

CCDC 1898970: Experimental Crystal Structure Determination

Related Article: M. Nieves Corella-Ochoa, Jesús B. Tapia, Heather N. Rubin, Vanesa Lillo, Jesús González-Cobos, José Luis Núñez-Rico, Salvador R.G. Balestra, Neyvis Almora-Barrios, Marina Lledós, Arnau Güell-Bara, Juanjo Cabezas-Giménez, Eduardo C. Escudero-Adán, Anton Vidal-Ferran, Sofía Calero, Melissa Reynolds, Carlos Martí-Gastaldo, José Ramón Galán-Mascarós|2019|J.Am.Chem.Soc.|141|14306|doi:10.1021/jacs.9b0650

CCDC 1898811: Experimental Crystal Structure Determination

Related Article: M. Nieves Corella-Ochoa, Jesús B. Tapia, Heather N. Rubin, Vanesa Lillo, Jesús González-Cobos, José Luis Núñez-Rico, Salvador R.G. Balestra, Neyvis Almora-Barrios, Marina Lledós, Arnau Güell-Bara, Juanjo Cabezas-Giménez, Eduardo C. Escudero-Adán, Anton Vidal-Ferran, Sofía Calero, Melissa Reynolds, Carlos Martí-Gastaldo, José Ramón Galán-Mascarós|2019|J.Am.Chem.Soc.|141|14306|doi:10.1021/jacs.9b0650

CCDC 1898971: Experimental Crystal Structure Determination

Related Article: M. Nieves Corella-Ochoa, Jesús B. Tapia, Heather N. Rubin, Vanesa Lillo, Jesús González-Cobos, José Luis Núñez-Rico, Salvador R.G. Balestra, Neyvis Almora-Barrios, Marina Lledós, Arnau Güell-Bara, Juanjo Cabezas-Giménez, Eduardo C. Escudero-Adán, Anton Vidal-Ferran, Sofía Calero, Melissa Reynolds, Carlos Martí-Gastaldo, José Ramón Galán-Mascarós|2019|J.Am.Chem.Soc.|141|14306|doi:10.1021/jacs.9b0650