Molecular Sciences

Molecular Recognition and Supramolecular Chemistry

A new line of research has been initiated by our research group at the institute, aimed at developing new chiral receptors of cations and peptidomimetics as simple molecular models for the study and understanding of non-covalent interactions.

The Molecular Recognition and Supramolecular Chemistry group profile page on Digital.CSIC.

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Reconocimiento
Presentation

These weak non-covalent interactions are responsible for the binding between receptor and substrate, and for the folding of organic molecules. This in turn gives rise to the different functions of biological molecules.

The knowledge and scope of these non-covalent interactions are essential for the development of diverse areas of knowledge, such as Biology, Chemistry, Medicine, Materials Science, etc.

 

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Fig.1

New Chiral Cation Receptors

Numerous biological and chemical processes are based on chiral recognition, such as: enzyme-substrate interactions, immune responses, mechanisms of action of drugs, storage and retrieval of genetic information, and asymmetric catalysis are some of the most relevant examples.

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Fig.4

Quantification of Non-Covalent Interaction

Using the design of the second generation of chiral cation receptors, we were able to synthesize several receptors that present good levels of chiral discrimination. Specifically, the receptor that incorporates 2,6-dicarbonyl-pyridine as spacer A and oxybis(ethanediil) as spacer B, is capable of...

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Fig.5

Chiral Recognition Reinforcement

Co-operation is one of the most fundamental concepts in molecular recognition and supramolecular self-assemblies. It explains how the behaviour of a system as a whole is different from what is expected of each of the individual isolated interactions. This is a fundamental phenomenon in the...

Peptide-Mimetic Design and Synthesis

The main objective of mimetic peptides is to imitate the peptide structure by means of models that have the functional groups spatially arranged in a controlled way. As they have similar characteristics to their natural counterparts, they have been used to replace substrates (peptides) of...

Receptores Quirales de Cationes y Foldámeros como Modelos para el Estudio del Plegamiento Molecular y sus Consecuencias

Año:2019
Director del trabajo:

Dr. Tomás Martín Ruiz

Estudiante:

Andrés Feher Voelger

Tipo:Tesis doctoral

Diseño y Síntesis de Nuevas Unidades de Aminoácidos no Naturales con Aplicación en la Formación de Péptidos Miméticos (DEA)

Año:2019
Director del trabajo:

Dr. Tomás Martín Ruiz

Estudiante:

Andrés Feher Voelger

Tipo:Máster y TFG

Uso de la Reacción de Nicholas Intermolecular y Metátesis de Cierre de Anillos en la Formación de Éteres Cíclicos con Alto Grado de Sustitución

Año:2019
Director del trabajo:

Dr. Victor S. Martín y Dr. Tomás Martín Ruiz

Estudiante:

Nuria Ortega Hernández

Tipo:Tesis doctoral

Uso de la Reacción de Nicholas Intermolecular y Metátesis de Cierre de Anillos en la Formación de Éteres Cíclicos con Alto Grado de Sustitución (DEA)

Año:2019
Director del trabajo:

Dr. Victor S. Martín y Dr. Tomás Martín Ruiz

Estudiante:

Nuria Ortega Hernández

Tipo:Máster y TFG

Aplicación de la Reacción de Nicholas en la Síntesis de Éteres Cíclicos

Año:2019
Director del trabajo:

Dr. Victor S. Martín y Dr. Tomás Martín Ruiz

Estudiante:

Fernando R. Pinacho Crisóstomo

Tipo:Tesis doctoral

Diseño, Síntesis y Estudio de Nuevos Receptores Quirales de Cationes (DEA)

Año:2019
Director del trabajo:

Dr. Victor S. Martín y Dr. Tomás Martín Ruiz

Estudiante:

Romen Carrillo Fumero

Tipo:Máster y TFG

Nuevos Receptores Quirales de Cationes: Diseño y Síntesis (TFM)

Año:2019
Director del trabajo:

Dr. Tomás Martín Ruiz

Estudiante:

Jorge Borges González

Tipo:Máster y TFG

Reacción de Nicholas Intramolecular Estereoselectiva empleando Epóxidos como Nucleófilos (DEA)

Año:2019
Director del trabajo:

Dr. Victor S. Martín y Dr. Tomás Martín Ruiz

Estudiante:

Fernando R. Pinacho Crisóstomo

Tipo:Máster y TFG

Del Reconocimiento Molecular a la Organocatálisis: La unidad de Tetrahidropirano como Motivo Estructural Privilegiado

Año:2019
Director del trabajo:

Dr. Tomás Martín Ruiz

Estudiante:

Jorge Borges González

Tipo:Tesis doctoral

Síntesis de Éteres Cíclicos a Través de Ciclaciones en Cascada de Epóxidos (DEA)

Año:2019
Director del trabajo:

Dr. Victor S. Martín y Dr. Tomás Martín Ruiz

Estudiante:

Julio Rodríguez López

Tipo:Tesis doctoral

Aplicación de análisis bayesiano a la evaluación de cálculos químico cuánticos dedicados a la determinación estructural de productos naturales

Año:2019
Director del trabajo:

Dr. Antonio Hernández Daranas, IPNA

Estudiante:

Lorena Morales Perez

Tipo:Máster y TFG
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INTERREG

MAC-INTERREG MIMAR+ "Seguimiento, control y mitigación de proliferaciones de organismos marinos asociadas a perturbaciones humanas y cambio climático en la Región Macaronésica"

Con MIMAR+ se consolidan y expanden los avances en el conocimiento de MIMAR, pretendiendo agrupar a los agentes interesados en toda la región bajo la cobertura de un…

Investigador principal:

Antonio Hdez. Daranas

Estado:

En Ejecución

Proyecto de investigación

Valorization of a marine natural product from the Canary Islands. Preformulation and in vivo proof of concept of the norzoanthamine potential for the treatment of cartilage disorders

Investigador principal:
Estado:

En Ejecución

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MINECO

Receptores Moleculares como Modelos para el Estudio de las Interacciones No Covalentes y sus Consecuencias

Investigador principal:

Tomás Martín Ruiz

Estado:

Finalizado

Proyecto de investigación

Asignación Estereoquímica de Moléculas Orgánicas Utilizando Métodos Computacionales y RMN

Investigador principal:

Dr. Antonio Hernández Daranas

Estado:

Finalizado

Proyecto de investigación

Desarrollo de Compuestos Bioactivos. Exploración de Nuevas Metodologías Sintéticas

Investigador principal:

Tomás Martín Ruíz

Margarita Cristina Brovetto Gelabert

Estado:

Finalizado

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MINECO

Receptores Quirales de Cationes y Péptido-Miméticos Como Modelos para el Estudio de las Interacciones No Covalentes y sus Implicaciones

Investigador principal:

Tomás Martín Ruíz

Estado:

Finalizado

Proyecto de investigación

Nuevos Receptores Quirales de Cationes: Diseño, Síntesis, Estudio Estructural y Aplicaciones. Aproximación al Diseño y la Síntesis de Péptido-Miméticos

Investigador principal:

Tomás Martín Ruíz

Estado:

Finalizado

Proyecto de investigación

Diseño, Síntesis y Estudio de Nuevos Receptores Quirales de Cationes. Aplicación a la Resolución de Mezclas Racémicas y a la Catálisis Asimétrica

Investigador principal:

Tomás Martín Ruíz

Estado:

Finalizado

Selected Publications

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Efficient synthesis of benzocyclotrimer

Efficient synthesis of benzocyclotrimer analogues by Negishi cross-coupling and intramolecular nucleophilic substitution

We report a new and efficient synthetic strategy that allows access to flexible and functionalized benzocyclotrimers under mild conditions and in few steps. The Negishi cross-coupling reaction was used for the C-C bond formation, whereas intramolecular O-alkylations provided the oxepane rings.

Borges-González, Jorge; Martín, Tomás

Chem. Commun. 54(4): 362-365 (2018)
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Tetrahydropyran‐Based Hybrid

Tetrahydropyran-based hybrid dipeptides as asymmetric catalysts for michael addition of Aldehydes to ß-Nitrostyrenes

A new series of hybrid dipeptide‐like organocatalysts based on pyranoid ϵ‐ or ζ‐amino acids and proline have been prepared for the asymmetric Michael addition of aldehydes to β‐nitrostyrenes. The reaction proceeds under mild conditions to afford a wide range of γ‐nitroaldehydes with up to 98% yield and up to 96% ee. These dipeptides are bifunctional organocatalysts, with a proline at the N‐terminus and a carboxylic acid at the C‐terminus. The tetrahydropyran unit embedded in the ϵ‐ or ζ‐amino acid induces a well‐defined conformation that is responsible for the catalysis. These dipeptides represent a new type of organocatalyst with a large number of possibilities to modulate their reactivity and selectivity.

Borges-González, Jorge; Feher Voelger, Andrés; Pinacho Crisóstomo, Fernando R.; Quintana Morales, Ezequiel; Martín, Tomás  

Advanced Synthesis and Catalysis 359(4): 576-583 (2017)
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Epoxide‐Opening Cascades

Epoxide-opening cascades triggered by a Nicholas reaction: Total synthesis of teurilene

Natural inspiration: Based on the biosynthesis of squalene‐derived polyethers, a total synthesis of teurilene is described. The carbocation formation in the Nicholas reaction serves to control the initiation of a polyepoxide ring‐opening cascade. The three furan rings present in teurilene were obtained in excellent yield in one step. Boc=tert‐butoxycarbonyl, TMS=trimethylsilyl.

Rodríguez-López, Julio; Pinacho Crisóstomo, Fernando R.; Ortega, Nuria; López Rodríguez, Matías; Martín, Víctor S.; Martín, Tomás

Angewandte Chemie - International Edition 52(13): 3659-3662 (2013)
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Application of isothermal titration calorimetry as a tool to study natural product interactions

Application of isothermal titration calorimetry as a tool to study natural product interactions

Over the past twenty-five years, isothermal titration calorimetry (ITC) has become a potent tool for the study a great variety of molecular interactions. This technique is able to provide a complete thermodynamic profile of an interaction process in a single experiment, with a series of advantages in comparison to other comparable techniques, such as less amount of sample or no need of chemical modification or labelling. It is thus not surprising that ITC has been applied to study the manifold types of interactions of natural products to get new insights into the molecular key factors implied in the complexation process of this type of compounds. This review provides an overview over the applications of ITC as a potent tool to investigate interactions of natural products with proteins, nucleic acids, oligosaccharides, and other types of receptors. The examples have been selected depending on the impact that this technique had during the investigation and revision of the interactions involved in the bioactivity of a compound, lead optimization or technical applications.

Callies, Oliver; Hernández Daranas, Antonio

 

 

Natural Product Reports 33(7): 881-904 (2016)
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Towards a Structural Basis for the Relationship Between Blood Group and the Severity of El Tor Cholera

Towards a Structural Basis for the Relationship Between Blood Group and the Severity of El Tor Cholera

It has long been known that people with blood group O are more severely affected by El Tor cholera than those with blood groups A or B. Microcalorimetry and NMR spectroscopy are used to evaluate the ability of the B‐subunits of cholera toxin and E. coli heat‐labile toxin to bind to selected blood group oligosaccharides.

Mandal, Pintu K.; Branson, Thomas R.; Hayes, Edward D.; Ross, James F.; Gavín, José A.; Hernández Daranas, Antonio; Turnbull, W. Bruce

Angewandte Chemie - International Edition 51(21): 5143-5146 (2012)
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Combining the Power of J Coupling and DP4 Analysis

Combining the Power of J Coupling and DP4 Analysis on Stereochemical Assignments: The J-DP4 Methods

A systematic study to include J couplings into DP4 formalism (J-DP4) led to the development of three alternative strategies. The dJ-DP4 (direct) approach involves a new DP4-like equation including an additional probability term given by J. The iJ-DP4 (indirect) approach explores the original DP4 method with a restricted conformational search. Despite both strategies performing better than DP4, their combined use (iJ/dJ-DP4) provided the best results, with a 2.5-fold performance improvement at similar or lower computational cost.

Grimblat, Nicolás; Gavín, José A.; Hernández Daranas, Antonio; Sarotti, Ariel M.

Organic Letters 21: 4003-4007 (2019)