Artificial enzymes:
Our dream is to synthesize an artificial enzyme with the catalytic activity that enzymes show in nature. To do this, we are conducting a systematic study of the active center of hydrolases, analysing the X-ray structure of their active center, to synthesize molecules that have a similar geometry.[1] We believe that by mimicking the geometry of the groups that give enzymes catalytic activity, we should be able to simulate their catalytic activity.
Molecular recognition of amino acids:
The group has extensive experience in the design of receptors for the enantioselective recognition of amino acids, by means of a well-established and easy-to-scale technique such as liquid-liquid extraction.[2] Due to the low solubility of amino acids in low-polar solvents, in the group the separation of amino acid derivatives has also been carried out.[3] In addition, the molecular receptors developed have shown sufficient selectivity for the separation of a given amino acid from a mixture of natural amino acids, which could be useful in obtaining compounds with added-value or in the preparation of food supplements for diets that require the suppression of a specific amino acid (as in the cases of phenylketonuria and tyrosinemia). In particular, in the last three years, several molecular receptors have been successfully synthesized that selectively allow the separation of alanine, proline or phenylalanine.[4]
Molecular recognition of other organic species of interest:
The molecular recognition of other species of interest has also been studied, such as anions, [5] diketopiperazines, [6] carboxylic acids [7] and hydroxycarboxylates.[8] Recently, a new line of research focused on the recognition of agonists and antagonists of the beta adrenergic receptor has been started, [9] among which are drugs of notable relevance, such as salbutamol or propanolol. The group is currently studying the possibility of optimizing this process to develop a viable technique from an industrial point of view.
Fluorescent sensors:
The group has vast experience in the handling and synthesis of fluorescent molecules, which also turn out to be suitable substrates to carry out association processes, thus making these molecules perfect candidates for the manufacture of optical sensors, since the association process goes accompanied by a variation of the optical properties. [10]
Organocatalysts and supramolecular catalysts:
We have an extensive experience in the development of supramolecular catalysts and organocatalysts inspired by enzymes. [11] Among them, the design of molecular receptors that mimics oxoanionic holes stands out, a structure present in many hydrolytic enzymes. Currently, the possibility of using these receptors as catalysts in organic reactions of interest, such as the transesterification reaction used in the production of biodiesel, is being studied. All these studies have led to publications in high-impact scientific journals, a patent, [12] as well as TFGs, TFMs and Doctoral Theses.
References:
[1] Garrido-González, J. J.; Iglesias Aparicio, Mª M.; Martínez García, M.; Simón. L.; Sanz, F.; Morán, J. R.; Fuentes de Arriba, Á. L. ACS Catal. 2020, 10, 11162.
[2] Hernández, J. V.; Oliva, A. I.; Simón, L.; Muñiz, F. M.; Mateos, A. A.; Morán, J. R., J. Org. Chem. 2003, 68, 7513.
[3] Oliva, A. I.; Simón, L.; Muñiz, F. M.; Sanz, F.; Morán, J. R., Chem. Commun. 2004, 426; Oliva, A. I.; Simón, L.; Muñiz, F. M.; Sanz, F.; Morán, J. R. Org. Lett. 2004, 6, 1155; Fuentes de Arriba, A. L.; Herrero, A. G.; Rubio, O. H.; Monleón, L. M.; Simón, L.; Alcázar, V.; Sanz, F.; Morán, J. R., Org. Biomol. Chem. 2015, 13, 493; de Juan Fernández, L.; Fuentes de Arriba, Á. L.; Monleón, L. M.; Rubio, O. H.; Alcázar Montero, V.; Simón Rubio, L.; Morán, J. R., Eur. J. Org. Chem. 2016, 1541.
[4] Temprano, A. G.; Monleón, L. M.; Rubio, O. H.; Simón, L.; Pérez, A. B.; Sanz, F.; Moran, J. R., Org. Biomol. Chem. 2015, 14, 1325; Gómez-Herrero, F.; Rubio, O. H.; Monleón, L. M.; Fuentes de Arriba, A. L.; Simón, L.; Morán, J. R., Org. Biomol. Chem. 2016, 14, 3906; Rubio, O. H.; Taouil, R.; Muniz, F. M.; Monleón, L. M.; Simón, L.; Sanz, F.; Morán, J. R., Org. Biomol. Chem. 2016, 15, 477.
[5] Blázquez, M. T.; Muñiz, F. M.; Saez, S.; Simón, L. M.; Alonso, A.; Raposo, C.; Lithgow, A.; Alcázar, V.; Morán, J. R., Heterocycles 2006, 69, 73; Fuentes de Arriba, A. L.; Turiel, M. G.; Simón, L.; Sanz, F.; Boyero, J. F.; Muñiz, F. M.; Morán, J. R.; Alcázar, V., Org. Biomol. Chem. 2011, 9, 8321.
[6] Martín, M.; Raposo, C.; Oliva, A. I.; Simón, L.; Caballero, C.; Morán, J. R., Chem. Lett. 2000, 718.
[7] Muñiz, F. M.; Simón, L.; Sáez, S.; Raposo, C.; Alcázar, V.; Moran, J. R., Sensors 2008, 8, 1637; Muñiz, F. M.; Alcázar, V.; Sanz, F.; Simón, L.; Fuentes de Arriba, Á. L.; Raposo, C.; Morán, J. R., Eur. J. Org. Chem. 2010, 6179.
[8] Oliva, A. I.; Simón, L.; Muñiz, F. M.; Sanz, F.; Morán, J. R., Eur. J. Org. Chem. 2004, 1698; Hernández Rubio, O.; Borrego, S. d. M.; Marcos Monleón, L.; Simón, L.; Temprano, Á. G.; Rodríguez Morán, J., Org. Biomol. Chem. 2017, 15, 4571.
[9] Fuentes de Arriba, A. L.; Simón, L.; Rubio, O. H.; Monleón, L. M.; Alcázar, V.; Sanz, F.; Raposo, C. A.; Morán, J. R., Chem. Commun. 2016, 52, 12582.
[10] Oliva, A. I.; Simón, L.; Muñiz, F. M.; Sanz, F.; Ruiz-Valero, C.; Morán, J. R., J. Org. Chem. 2004, 69, 6883.
[11] Simón, L.; Muñiz, F. M.; Sáez, S.; Raposo, C.; Sanz, F.; Morán, J. R., Helv. Chim. Acta 2005, 88, 1682; Simón, L.; Muñiz, F. M.; Sáez, S.; Raposo, C.; Morán, J. R., Eur. J. Org. Chem. 2007, 4821; Simón, L.; Muñiz, F. M.; Sáez, S.; Raposo, C.; Morán, J. R., Eur. J. Org. Chem. 2008, 2397-2403; Rubio, O. H.; Fuentes de Arriba, Á. L.; Monleón, L. M.; Sanz, F.; Simón, L.; Alcázar, V.; Morán, J. R., Tetrahedron 2015, 71, 1297; Fuentes de Arriba, Á. L.; Rubio, O. H.; Simón, L.; Alcázar, V.; Monleón, L. M.; Sanz, F.; Morán, J. R., Tetrahedron: Asymmetry 2017, 28, 819.
[12] Fuentes de Arriba, Á. L.; Simón, L.; Alcázar, V.; Cuellar, J.; Lozano-Martínez, P.; Morán, J. R., Adv. Synth. Catal. 2011, 353, 2681; Alegría, A.; Fuentes de Arriba, Á. L.; Morán, J. R.; Cuellar, J., Appl. Catal. B: Environ. 2014, 160-161, 743; “Derivados de ácido sulfónico para síntesis de biodiésel”, Morán, J. R.; Cuellar, J.; Fuentes de Arriba, Á. L., ES2393352, 2012.
