Multicomponent reactions (MCRs) encompass an exciting class of chemical transformations that have proven success in almost all fields of synthetic organic chemistry. These convergent procedures incorporate three or more reactants into a final product in one pot, thus combining high levels of complexity and diversity generation with low synthetic cost. Striking applications of these processes are found in heterocycle, peptidomimetic, and natural product syntheses. However, their potential in the preparation of large macro- and biomolecular constructs has been realized just recently. This Account describes the most relevant results of our group in the utilization of MCRs for ligation/conjugation of biomolecules along with significant contributions from other laboratories that validate the utility of this special class of bioconjugation process. Thus, MCRs have proven to be efficient in the ligation of lipids to peptides and oligosaccharides as well as the ligation of steroids, carbohydrates, and fluorescent and affinity tags to peptides and proteins. In the field of glycolipids, we highlight the power of isocyanide-based MCRs with the one-pot double lipidation of glycan fragments functionalized as either the carboxylic acid or amine. In peptide chemistry, the versatility of the multicomponent ligation strategy is demonstrated in both solution-phase lipidation protocols and solid-phase procedures enabling the simultaneous lipidation and biotinylation of peptides. In addition, we show that MCRs are powerful methods for synchronized lipidation/labeling and macrocyclization of peptides, thus accomplishing in one step what usually requires long sequences. In the realm of protein bioconjugation, MCRs have also proven to be effective in labeling, site-selective modification, immobilization, and glycoconjugation processes. For example, we illustrate a successful application of multicomponent polysaccharide-protein conjugation with the preparation of multivalent glycoconjugate vaccine candidates by the ligation of two antigenic capsular polysaccharides of a pathogenic bacterium to carrier proteins. By highlighting the ability to join several biomolecules in only one synthetic operation, we hope to encourage the biomolecular chemistry community to apply this powerful chemistry to novel biomedicinal challenges.

This research proposes the rational modeling, synthesis and evaluation of film dressing hydrogels based on polyvinyl alcohol crosslinked with 20 different kinds of dicarboxylic acids. These formulations would allow the sustained release of simultaneous bioactive compounds including allantoin, resveratrol, dexpanthenol and caffeic acid as a multi-target therapy in wound healing. Interaction energy calculations and molecular dynamics simulation studies allowed evaluating the intermolecular affinity of the above bioactive compounds by hydrogels crosslinked with the different dicarboxylic acids. According to the computational results, the hydrogels crosslinked with succinic, aspartic, maleic and malic acids were selected as the best candidates to be synthesized and evaluated experimentally. These four crosslinked hydrogels were prepared and characterized by FTIR, mechanical properties, SEM and equilibrium swelling ratio. The sustained release of the bioactive compounds from the film dressing was investigated in vitro and in vivo. The in vitro results indicate a good release profile for all four analyzed bioactive compounds. More importantly, in vivo experiments suggest that prepared formulations could considerably accelerate the healing rate of artificial wounds in rats. The histological studies show that these formulations help to successfully reconstruct and thicken epidermis during 14 days of wound healing. Moreover, the four film dressings developed and exhibited excellent biocompatibility. In conclusion, the novel film dressings based on hydrogels rationally designed with combinatorial and sustained release therapy could have significant promise as dressing materials for skin wound healing.

We investigated the potential of two oil extracts from seeds of Colliguaya integerrima (CIO) and Cynara cardunculus (CO) to use as nutritionally edible oils. For this purpose, oil quality was accessed by determining the fatty acid composition, peroxide value, acid value, iodine value, saponification number, phenolic contents, and oxidative stability during thermally induced oxidation of CIO and CO oils and compared to those of extra-virgin olive oil (EVOO). The chemical composition results demonstrated that both oils could be nutritional sources of essential unsaturated fatty acids. Moreover, according to the gravimetric analysis, the main decomposition step occurred in the temperature range of 200–420 °C, showing a similar thermal behavior of EVOO oil. However, CO and EVOO oils showed a higher phenolic content at degradation onset temperature (T0) in contrast with CIO oil. The antioxidant activity of the different studied oils showed a direct correlation with the phenol contents, up to temperatures around 180 °C, where the percentage of free radical scavenging assay for EVOO was higher than CO in contrast with the TPC values. Finally, we analyzed the minor components before and after heating CIO and CO at 180 °C by gas chromatography–mass spectrometry (GC–MS) using library search programs.

This study describes the in-silico rational design, synthesis and evaluation of cross-linked polyvinyl alcohol hydrogels containing γ-cyclodextrin (γ-CDHSAs) as platforms for the sustained release of prednisone (PDN). Through in-silico studies using semi-empirical quantum mechanical calculations, the effectiveness of 20 dicarboxylic acids to generate a specific cross-linked hydrogel capable of supporting different amounts of γ-cyclodextrin (γ-CD) was evaluated. According to the interaction energies calculated with the in-silico studies, the hydrogel made from PVA cross-linked with succinic acids (SA) was shown to be the best candidate for containing γ-CD. Later, molecular dynamics simulation studies were performed in order to evaluate the intermolecular interactions between PDN and three cross-linked hydrogel formulations with different proportions of γ-CD (2.44%, 4.76% and 9.1%). These three cross-linked hydrogels were synthesized and characterized. The loading and the subsequent release of PDN from the hydrogels were investigated. The in-silico and experimental results showed that the interaction between PDN and γ-CDHSA was mainly produced with the γ-CDs linked to the hydrogels. Thus, the unique structures and properties of γ-CDHSA demonstrated an interesting multiphasic profile that could be utilized as a promising drug carrier for controlled, sustained and localized release of PDN.

This study describes the absorption of methamidophos (MMP) from aqueous solution by crosslinked poly(vinyl alcohol) (PVA) hydrogel synthesized using malic acid (MA) as a crosslinker (CLPHMA). The prepared hydrogels were characterized by FTIR spectroscopy, scanning electron microscopy, and the thermal properties were studied by using thermal gravimetric analysis. Also, the swelling index as a function of PVA:MA composition and pH were studied. An in silico rational study, which involved all‐atom molecular dynamics simulations of PVA:MA systems in proportions 10:2, 10:4, and 10:6 was performed. The in silico studies concluded that the more suitable crosslinking degree for MMP pesticide removal is with the 20% (wt %) of crosslinker (CLPHMA‐20). The experimental analysis of MMP removal with CLPHMA was performed as well. It was found that the prepared CLPHMA‐20 had a great efficiency to recover around 86% of MMP from their solutions. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 45964.