Metal-organic frameworks (MOFs) bring new life to hydrogen-bonding organocatalysts in confined spaces

Hydrogen-bonding organocatalysis has emerged as a promising biomimetic alternative to Lewis acid catalysis. Urea, thiourea and squaramide moieties represent the most common hydrogen-bond donors used for the preparation of these catalysts. However, their significant tendency to undergo self-quenching (self-aggregation) often decreases their solubility and reactivity. Recently, scientists have found a promising way around this problem by immobilizing the hydrogen-bonding organocatalysts on metal–organic frameworks (MOFs). Along with advantageous modular synthesis and recycling properties, the tunable porosity and topology of MOFs also allows fast mass transport and/or interactions with substrates. Herein, we highlight the existing examples dealing with the fabrication and testing of hydrogen-bonding organocatalyst-containing MOFs, providing also our vision for further advances in this area. The results derived from these studies will likely serve as inspiration for the future development of superior hydrogen-bonding organocatalysts to accomplish in confined spaces chemical transformations that are either slow or unaffordable under standard homogeneous conditions

Self-Assembly of Hollow Organic Nanotubes Driven by Arene Regioisomerism

Arene regioisomerism in low-molecular-weight gelators can be exploited as a tool to modulate the micro-structures of the corresponding xerogel networks by using the three different possible substitution patterns ortho, meta and para. This aromatic regioisomer-driven strategy has been used with a cholesterol-based gelator to prepare hollow self-assembled organic nanotubes (S-ONTs) with inside and outside diameters of ca. 35 and 140 nm, respectively. Electron microscopy imaging and theoretical calculations were employed to rationalize the formation mechanism of these S-ONTs. From the three possible regioisomers, only the ortho-disubstituted cholesteryl-based gelator showed the optimal angle and distance between substituents to afford the formation of the cyclic assemblies required for nanotube growth by assembling 30–40 units of the gelator. This study opens fascinating opportunities to expand the synthesis of controllable and unique microstructures by modulating geometrical parameters through aromatic regioisomers.Deutsche ForschungsgemeinschaftUniversität RegensburgFundación BBVAMinisterio de Economía, Industria y CompetitividadGobierno de Aragón-Fondo Social EuropeoExtreme Science and Engineering Discovery EnvironmentMinisterio de Ciencia, Innovación y Universidade

AQME: Automated quantum mechanical environments for researchers and educators

AQME, automated quantum mechanical environments, is a free and open-source Python package for the rapid deployment of automated workflows using cheminformatics and quantum chemistry. AQME workflows integrate tasks performed across multiple computational chemistry packages and data formats, preserving all computational protocols, data, and metadata for machine and human users to access and reuse. AQME has a modular structure of independent modules that can be implemented in any sequence, allowing the users to use all or only the desired parts of the program. The code has been developed for researchers with basic familiarity with the Python programming language. The CSEARCH module interfaces to molecular mechanics and semi-empirical QM (SQM) conformer generation tools (e.g., RDKit and Conformer–Rotamer Ensemble Sampling Tool, CREST) starting from various initial structure formats. The CMIN module enables geometry refinement with SQM and neural network potentials, such as ANI. The QPREP module interfaces with multiple QM programs, such as Gaussian, ORCA, and PySCF. The QCORR module processes QM results, storing structural, energetic, and property data while also enabling automated error handling (i.e., convergence errors, wrong number of imaginary frequencies, isomerization, etc.) and job resubmission. The QDESCP module provides easy access to QM ensemble-averaged molecular descriptors and computed properties, such as NMR spectra. Overall, AQME provides automated, transparent, and reproducible workflows to produce, analyze and archive computational chemistry results. SMILES inputs can be used, and many aspects of tedious human manipulation can be avoided. Installation and execution on Windows, macOS, and Linux platforms have been tested, and the code has been developed to support access through Jupyter Notebooks, the command line, and job submission (e.g., Slurm) scripts. Examples of pre-configured workflows are available in various formats, and hands-on video tutorials illustrate their use

Self-assembled fibrillar networks of a multifaceted chiral squaramide: supramolecular multistimuli-responsive alcogels

Chiral N,N'-disubstituted squaramide 1 has been found to undergo self-assembly in a variety of alcoholic solvents at low concentrations leading to the formation of novel nanostructured supramolecular alcogels. The gels responded to thermal, mechanical, optical and chemical stimuli. Solubility studies, gelation ability tests and computer modeling of a series of structurally related squaramides proved the existence of a unique combination of non-covalent molecular interactions and favorable hydrophobic/hydrophilic balance in 1 that drive the anisotropic growth of alcogel networks. The results have also revealed a remarkable effect of ultrasound on both the gelation kinetics and the properties of the alcogels

Enantioselective C-P Bond Formation through C(sp3)-H Functionalization

An enantioselective C−P bond formation has been developed through a C(sp3)−H activation in an oxidation step followed by an organocatalyzed hydrophosphonylation protocol. The asymmetric organocatalytic Pudovik reaction has been achieved following a one‐pot strategy, starting from different benzylic and allylic alcohols and dibenzyl phosphite, using MnO2 as the oxidant and a chiral squaramide as organocatalyst. The scope of the reaction provides enantiomerically enriched α‐hydroxy phosphonates with yields from 40% to >95% and enantioselectivities from 64% to >99%. Furthermore, the use of this methodology has been demonstrated to form a tetrasubstituted carbon stereocenter, generating an acetophenone derivative in situ, using diphenyl phosphite. Therefore, this approach represents an asymmetric strategy for constructing chiral C−P bonds, which are of interest to the pharmaceutical industry

Experimental and computational studies of the production of 1,3-butadiene from 2,3-butanediol using SiO2-supported H3PO4 derivatives

Silica-supported phosphoric acid and metal phosphate catalyzed 1,3-butadiene (BDE) production from 2,3-butanediol (2,3-BDO) was studied using experimental and computational techniques. The catalyst was initially tested in a continuous flow reactor using commercially available 2,3-BDO, leading to maximum BDE yields of 63C%. Quantum chemical mechanistic studies revealed 1,2-epoxybutane is a kinetically viable and thermodynamically stable intermediate, supported by experimental demonstration that this epoxide can be converted to BDE under standard reaction conditions. Newly proposed E2 and SN2′ elementary steps were studied to rationalize the formation of BDE and all detected side-products. Additionally, using quantum mechanics/molecular mechanics (QM/MM) calculations, we modeled silica-supported phosphate catalysts to study the effect of the alkali metal center. Natural population analysis showed that phosphate oxygen atoms are more negatively charged in CsH2PO4/SiO2 than in H3PO4/SiO2. In combination with temperature-programmed desorption experiments using CO2, the results of this study suggest that the improved selectivity achieved when adding the metal center is related to an increase in the basicity of the catalyst.R.S.P. and J.V.A.-R. acknowledge the RMACC Summit supercomputer, supported by the NSF (ACI-1532235 and ACI1532236), and the Extreme Science and Engineering Discovery Environment (XSEDE) allocations TG-CHE180056 and TG-CHE200033. J.V.A.-R. acknowledges financial support through the Gobierno de Aragón-Fondo Social Europeo (Research Group E07_23R) and a Juan de la Cierva Incorporación contract from the Ministry of Science and Innovation (MCIN) and the State Research Agency (AEI) of Spain, and the European Union (NextGenerationEU/PRTR) under grant reference IJC2020-044217-I. S.K. acknowledges XSEDE allocation TG-CHE210034 and the National Renewable Energy Laboratory Computational Science Center. This work was authored in part by the National Renewable Energy Laboratory, managed and operated by Alliance for Sustainable Energy, LLC, for the U.S. Department of Energy (DOE) under Contract No. DE-AC36-08GO28308. Funding was provided by U.S. Department of Energy Office of Energy Efficiency and Renewable Energy Bioenergy Technologies Office and in collaboration with the Consortium for Computational Physics and Chemistry (CCPC) and the Chemical Catalysis for Bioenergy Consortium (ChemCatBio). G.R.H., X.H., F.G.B, K.A.U., B.C.K., R.E.D., and D.R.V. acknowledge funding from the Chemical Catalysis for Bioenergy consortium by the Bioenergy Technologies Office in the DOE Office of Energy Efficiency and Renewable Energy. Microscopy was performed in collaboration with the Chemical Catalysis for Bioenergy Consortium under contract no. DE-AC05-00OR22725 with Oak Ridge National Laboratory (ORNL) and through a user project supported by ORNL’s Center for Nanophase Materials Sciences (CNMS), which is sponsored by the Scientific User Facilities Division, Office of Basic Energy Sciences, U.S. Department of Energy. Part of the microscopy research was also supported by the Office of Nuclear Energy, Fuel Cycle R&D Program and the Nuclear Science User Facilities. The results and analysis presented in this paper were partially possible thanks to the access granted to computing resources at the Galicia Supercomputing Center, CESGA, including access to the FinisTerrae supercomputer, the Red Española de Supercomputación (grant number QH-2023-1-0003) and the Drago cluster facility of SGAI-CSIC.Peer reviewe

Squaramides, discovering a new crucial scaffold

Spotlight 456Peer reviewe

Synthesis of squaramides and their application in organocatalysis computational and experimental studies

Las escuaramidas han resultado ser compuestos de marcado interés en distintas ramas de la química. El uso de las escuaramidas quirales como organocatalizadores es interesante ya que, usando la escuaramida adecuada, se crean entornos quirales ideales para la obtención de productos enriquecidos enantioméricamente mediante la formación de enlaces de hidrógeno con los sustratos. Una de las líneas principales de investigación de nuestro grupo es la síntesis y la aplicación organocatalítica de este tipo de compuestos, lo que nos ha llevado a desarrollar durante esta tesis doctoral reacciones quirales poco exploradas anteriormente en esta área. En primer lugar, es muy importante disponer de un método eficaz de síntesis de escuaramidas, motivos estructurales centro de investigaciones posteriores. La síntesis tradicional de escuaramidas consta de dos reacciones independientes de adición de aminas. Sin embargo, a través del diseño de un método de síntesis one-pot, conseguimos sintetizar las escuaramidas empleando un único reactor, con las ventajas asociadas de ahorro de tiempo, energía, dinero, menor generación de residuos, etc. Una de nuestras mayores prioridades dentro de esta tesis ha sido el desarrollo de reacciones organocatalíticas usando escuaramidas que dan lugar a productos enantioméricamente enriquecidos con potencial actividad biológica. A lo largo de esta tesis doctoral, desarrollamos la reacción de Henry catalizada por escuaramidas, obteniéndose los correspondientes β-nitroalcoholes con muy buenos rendimientos y enantioselectividades. Además, en algunos casos la carga catalítica requerida fue de tan sólo 0.25 mol%, siendo la más baja conocida para esta reacción en el campo de la organocatálisis. Asimismo, también estudiamos el mecanismo de la reacción de Henry catalizada por una escuaramida que contiene un grupo NOBIN. Para ello, realizamos distintos estudios computacionales en combinación con los propios datos experimentales. Además, exploramos distintas combinaciones de métodos y conjuntos de funciones de base para averiguar cuál de ellas llevaba a los mejores resultados. En este trabajo, la combinación más precisa fue la formada por el funcional ωB97X-D y el conjunto de funciones 6-311G(d). Este análisis representa el primer ejemplo en el cual se compara la eficiencia de distintas aproximaciones computacionales en la catálisis con escuaramidas. Además, se observó que en esta reacción existe un modo de interacción peculiar que nunca antes se había visto en catálisis, llamado “push-pull π+/π-”. Este modo consiste en dos interacciones π creadas por los anillos aromáticos de un grupo naftilo del catalizador con dos átomos del grupo aldehído, uno δ+ (su átomo de hidrógeno) y el otro δ- (su átomo de oxígeno).Peer reviewe

ROBERT raw data

<p>These folders contain the raw inputs and outputs from the workflows presented in the ROBERT manuscript, including:</p><p> </p><p>- Examples A-F from the benchmarking study (run in CESGA, 8 processors Intel Xeon Ice Lake 8352Y)</p><p>- Examples A-B from the SMILES workflows (run in DRAGO, 8-16 processors Intel Xeon Gold 6248R)</p><p>- Example of the discovery of Pd complexes (run in DRAGO, 8 processors Intel Xeon Gold 6248R)</p><p> </p><p>In all cases, an SH script is provided with the script submitted to the CESGA or DRAGO HPCs.</p&gt

Guanidine motif in biologically active peptides

In the past decade, guanidines have attracted attention as valuable hydrogen bond-based catalysts while they have long been considered as organic superbases with a broad scope of synthetic applicability. Their easy modification has also expanded their capacity to form complexes with a wide range of metal salts as effective metal scavengers. All these attractive aspects have promoted a huge growth in the field of organic synthesis involving guanidines and examples of such reactions have been collected in numerous reviews and some books. Moreover, this structural motif is also present in a large number of natural products and biologically active compounds that exhibit appealing properties and play important roles in medicinal chemistry. In this highlight, we will only cover the synthesis and properties of biologically active guanidine-containing peptides reported in the past 3 years. © CSIRO 2014.We thank the Spanish Ministry of Economía y Competitividad (MICINN. Madrid. Spain. Project CTQ2010-19606) and the Government of Aragón (Zaragoza. Spain. Research Group E-10) for financial support of our research.Peer Reviewe