Solid-Phase Lipase-CuNPs Biohybrids as Catalysts for One-Pot Parallel Synthesis of 2,3,4-Triacetyl-D-Gluconic Acid

Solid-phase lipase/metal nanobiohybrids, generated by growth of copper nanoparticles on enzyme matrixes immobilized on graphene, were used as heterogeneous catalysts with dual-activity for the regioselective production of 2,3,4-triacetyl-D-gluconic acid from α-peracetylated-glucose in a one-pot parallel process combining a lipase-mediated regioselective hydrolytic monodeprotection with a metal-catalyzed oxidation in aqueous media. A novel synthetic strategy, based on the in situ fabrication of Cu nanoparticles induced by lipase molecules specifically immobilized on a multi-layer graphene material by interfacial adsorption fixing them in the active open conformation, has been described. Thermomyces lanuginosus lipase was firstly used to prepare the functionalized multi-layer graphene from graphite as a biographene preparation (Biographene, BIOG), support used to successfully immobilize Candida rugosa lipase (CRL). This immobilized form BIOG-CRL was further used to create successful active bifunctional enzyme-metal nanoarchitectures. Two different Cu-lipase hybrids were synthesised, where Cu species and nanoparticles size were different depending on the methodology. Regioselectivity and stability of the hybrids were evaluated successfully in the production of monosaccharide building blocks, besides the robustness of the hybrids in recyclability experiments. These findings highlight the potential of these solid-phase nanoarchitectures as useful tools in the synthesis of complex glycoderivatives for use in food, medicine, and cosmetics

Synthesis of silver and gold nanoparticles-enzyme-polymer conjugate hybrids as dual-activity catalysts for chemoenzymatic cascade reactions

Novel hybrids containing silver or gold nanoparticles have been synthesized in aqueous media and at room temperature using enzymes or tailor-made enzyme-polymer conjugates, which directly induced the formation of inorganic silver or gold species. The choice of pH, protein, or bioconjugate strongly affected the final metallic nanoparticles hybrid formation. Using Candida antarctica lipase (CALB) in a solution, nanobiohybrids containing Ag2O nanoparticles of 9 nm average diameter were obtained. The use of tailor-made bioconjugates, for example, the CALB modified with dextran-aspartic acid polymer (Dext6kDa), resulted in a nanobiohybrid containing smaller Ag(0)/Ag2O nanoparticles. In the case of nanobiohybrids based on gold, Au(0) species were found in all cases. The Au-CALB hybrid contained spherical nanoparticles with 18 nm average diameter size, with a minor range of larger ones (>100 nm) while the AuNPs-CALB-Dext6kDa hybrid was formed by much smaller nanoparticles (9 nm, minor range of 22 nm), and also nanorods of 20-30/40-50 nm length. Using Thermomyces lanuginosus lipase (TLL), apart from the nanoparticle formation, nanoflowers with a diameter range of 100-200 nm were obtained. All nanobiohybrids maintained (dual) enzymatic and metallic activities. For instance, these nanobiohybrids exhibited exquisite dual-activity for hydrolysis/cycloisomerization cascades starting from allenic acetates. By merging the transition metal reactivity with the inherent lipase catalysis, allenic acetates directly converted to the corresponding O-heterocycles in enantiopure form catalysed by AgNPs-CALB-Dext6kDa, taking advantage of a kinetic resolution/cyclization pathway. These results showed the high applicability of these novel hybrids, offering new opportunities for the design of novel reaction cascades.Peer reviewe

application in C-H activation catalysis

This work was supported by the Spanish Government, the Spanish National Research Council (CSIC). We also thank Dr Martinez from Novozymes. Publisher Copyright: © 2023 RSC.The effect of the temperature in the synthesis of Pd nanoparticles in the metal-enzyme biohybrids is evaluated. The effect on the formation, size, and morphology of nanoparticles was evaluated using C. antarctica B lipase as the protein scaffold. XRD analyses confirmed the formation of crystalline Pd(0) as the metal species in all cases. TEM analyses revealed spherical crystalline nanoparticles with average diameter size from 2 nm at 4 °C synthesis to 10 nm obtained at 50 °C synthesis. The thermal phenomenon was also critical in the final hybrid formation using more complex enzymes, where the relation of the protein structure and temperature and the influence of the latter has been demonstrated to be critical in the reducing efficiency of the enzyme in the final Pd nanoparticle formation, in the metal species, or even in the final size of the nanoparticles. Different Pd biohybrids were evaluated as catalysts in the C-H activation of protected l-tryptophan under mild conditions. Pd@CALB4 showed the best results, with >99% conversion for C-2 arylation in methanol at room temperature with a TOF value of 64 min−1, being 2 or 4 times higher than that of the other synthesized hybrids. This catalyst showed a very high stability and recyclability, maintaining >95% activity after three cycles of use.publishersversionpublishe

Copper(i) as a reducing agent for the synthesis of bimetallic PtCu catalytic nanoparticles

Funding Information: This work received financial support from PT national funds (FCT/MCTES, Fundação para a Ciência e Tecnologia and Ministério da Ciência, Tecnologia e Ensino Superior) through the projects UIDB/50006/2020 and UIDP/50006/2020. S. N., C. L., J. L. C., A. F. L., and J. F. L. are thankful for the financial support from national funds (FCT/MCTES, Fundação para a Ciência e Tecnologia and Ministério da Ciência, Tecnologia e Ensino Superior) through project Met4Cat, EXPL/QUI-COL/0263/2021. This work was supported by the Spanish Government and the Spanish National Research Council (CSIC) (project PIE 201980E081). We thank the financial support by the PROTEOMASS Scientific Society (Portugal) (General Funding Grant 2022). S. N. thanks FCT/MCTEC (Fundação para a Ciência e Tecnologia and Ministério da Ciência, Tecnologia e Ensino Superior) Portugal for her doctoral grant associated with the Chemistry PhD program (SFRH/ BD/144618/2019). J. F. L. thanks FCT for the research contract through the Program DL 57/2016–Norma Transitória. A. F. L., J. F. L., S. N., J. L. C., and C. L. thank FCT/MCTES (Fundação para a Ciência e Tecnologia and Ministério da Ciência, Tecnologia e Ensino Superior) for the national funds received through the project SiSi4Bacter PTDC/QUI-COL/1517/2020. This work was carried out in part through the use of the INL user facilities. The authors thank Dr Jamila Djafari for the conceptualization and design of the graphical abstract. We also thank Ramiro Martínez from Novozymes for the gift of enzymes. Funding Information: This work received financial support from PT national funds (FCT/MCTES, Fundação para a Ciência e Tecnologia and Ministério da Ciência, Tecnologia e Ensino Superior) through the projects UIDB/50006/2020 and UIDP/50006/2020. S. N., C. L., J. L. C., A. F. L., and J. F. L. are thankful for the financial support from national funds (FCT/MCTES, Fundação para a Ciência e Tecnologia and Ministério da Ciência, Tecnologia e Ensino Superior) through project Met4Cat, EXPL/QUI-COL/0263/2021. This work was supported by the Spanish Government and the Spanish National Research Council (CSIC) (project PIE 201980E081). We thank the financial support by the PROTEOMASS Scientific Society (Portugal) (General Funding Grant 2022). S. N. thanks FCT/MCTEC (Fundação para a Ciência e Tecnologia and Ministério da Ciência, Tecnologia e Ensino Superior) Portugal for her doctoral grant associated with the Chemistry PhD program (SFRH/ BD/144618/2019). J. F. L. thanks FCT for the research contract through the Program DL 57/2016-Norma Transitória. A. F. L., J. F. L., S. N., J. L. C., and C. L. thank FCT/MCTES (Fundação para a Ciência e Tecnologia and Ministério da Ciência, Tecnologia e Ensino Superior) for the national funds received through the project SiSi4Bacter PTDC/QUI-COL/1517/2020. This work was carried out in part through the use of the INL user facilities. The authors thank Dr Jamila Djafari for the conceptualization and design of the graphical abstract. We also thank Ramiro Martínez from Novozymes for the gift of enzymes. Publisher Copyright: © 2023 RSCThis work investigates the potential utilization of Cu(i) as a reducing agent for the transformation of the platinum salt K2PtCl4, resulting in the production of stable nanoparticles. The synthesized nanoparticles exhibit a bimetallic composition, incorporating copper within their final structure. This approach offers a convenient and accessible methodology for the production of bimetallic nanostructures. The catalytic properties of these novel nanomaterials have been explored in various applications, including their use as artificial metalloenzymes and in the degradation of dyes. The findings underscore the significant potential of Cu(i)-mediated reduction in the development of functional nanomaterials with diverse catalytic applications.publishersversionepub_ahead_of_prin

Safety and efficacy of ribociclib plus letrozole in patients with HR+, HER2– advanced breast cancer: Results from the Spanish sub-population of the phase 3b CompLEEment-1 trial

Background: Breast cancer is the most common malignancy and the second leading cause of cancer-related mortality in Spanish women. Ribociclib in combination with endocrine therapy (ET) has shown superiority in prolonging survival in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) vs. ET alone.Methods: CompLEEment-1 is a single-arm, open-label phase 3b trial evaluating ribociclib plus letrozole in a broad population of patients with HR+, HER2- ABC. The primary endpoints were safety and tolerability. Here we report data for Spanish patients enrolled in CompLEEment-1.Results: A total of 526 patients were evaluated (median follow-up: 26.97 months). Baseline characteristics showed a diverse population with a median age of 54 years. At study entry, 56.5% of patients had visceral metastases and 8.7% had received prior chemotherapy for advanced disease. Rates of all-grade and Grade >= 3 adverse events (AEs) were 99.0% and 76.2%, respectively; 21.3% of patients experienced a serious AE, and 15.8% of AEs led to treatment discontinuation. AEs of special interest of neutropenia, increased alanine aminotransferase, increased aspartate aminotransferase and QTcF prolongation occurred in 77.8%, 14.8%, 11.4% and 4.0% of patients, respectively. Patients aged >70 years experienced increased rates of all-grade and Grade >= 3 neutropenia and anemia. Efficacy results were consistent with the global study.Conclusions: Results from Spanish patients enrolled in CompLEEment-1 are consistent with global data showing efficacy and a manageable safety profile for ribociclib plus letrozole treatment in patients with HR+, HER2-ABC, including populations of interest (NCT02941926).Trial registration: ClinicalTrials.gov NCT0294192

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Graphene-TLL-Cu2ONPs Hybrid as Highly Efficient Catalyst for Degradation of Organic Compounds

In this work, Cu2O nanoparticles (NPs) were created in situ on graphene functionalized with Thermomyces lanuginosus lipase (G@TLL) where site-oriented supported TLL acted as template and binder in the presence of copper salt by tailorable synthesis under mild conditions, producing a heterogeneous catalyst. Cu2O NPs were confirmed by XRD and XPS. The TEM microscopy showed that the nanoparticles were homogeneously distributed over the G@TLL surface with sizes of 53 nm and 165 nm. This G@TLL-Cu2O hybrid was successfully used in the degradation of toxic organic compounds such as trichloroethylene (TCE) and Rhodamine B (RhB). In the case of TCE, the hybrid presented a high catalytic capacity, degrading 60 ppm of product in 60 min in aqueous solution and room temperature without the formation of other toxic subproducts. In addition, a TOF value of 7.5 times higher than the unsupported counterpart (TLL-Cu2O) was obtained, demonstrating the improved catalytic efficiency of the system in the solid phase. The hybrid also presented an excellent catalytic performance for the degradation of Rhodamine B (RhB) obtaining a complete degradation (48 ppm) in 50 min in aqueous solution and room temperature and with the presence of a green oxidant as H2O2

Enzyme-Graphene Nanometal biohybrid Architectures as Highly Efficient Multifunctional Catalysts for Cascade Reactions

The development of new catalytic systems with different chemo- and biocatalytic functionalities for sustainable one-pot multistep transformations represents a big challenge in modern chemistry. Here, we have designed and synthesized novel enzyme-graphene nanometal hybrids of palladium and copper as multiactive heterogeneous catalysts. The in-situ formation of metallic nanoparticles of different size and species on enzymes (C. antartica lipase, CALB and and T. lanuginosus lipase), TLL) immobilized on multilayer graphene-anchored enzymes (G@CALB and G@TLL preparations) at room temperature and aqueous media allowed to create different kind of enzyme-metal nanoarchitectures, containing up to two enzymes and metallic nanoparticles of two different metals in the same compartment. The metallic nanoparticles were synthesized exclusively induced by the enzyme, homogeneously distributed on the enzymatic structure used as scaffold. The cooperative and synergistic participation of different chemo and biocatalytic components in the reduction process and especially in different cascade reactions was demonstrated. Domino cascade in aqueous media (enzymatic hydrolysis, metal reduction, and metal oxidation) was successfully performed from the different hybrid systems. The synthesis of glycoderivatives, transforming selectively peracetylated glucal to novel disaccharides, using G@CALB-Cu3(PO4)2NPs and G@CALB-Cu(0)NPs or α-peracetylated glucose to diacetyl-gluconic acid by G@TLL@CRL-Cu3(PO4)2NPs was successfully performed. Finally, the successful application in the dynamic kinetic resolution of racemic arylamine (>99% conversion and ee) in organic solvent catalyzed by G@CALB-Pd(0)NPs-Cu3(PO4)2NPs demonstrated the potential effect in synthetic chemistry, and the synergistic effect of catalysis between enzyme and metals. Furthermore, recycling studies demonstrated the high robustness of them

Graphene-TLL-Cu₂ONPs Hybrid as Highly Efficient Catalyst for Degradation of Organic Compounds

In this work, Cu2O nanoparticles (NPs) were created in situ on graphene functionalized with Thermomyces lanuginosus lipase (G@TLL) where site-oriented supported TLL acted as template and binder in the presence of copper salt by tailorable synthesis under mild conditions, producing a heterogeneous catalyst. Cu2O NPs were confirmed by XRD and XPS. The TEM microscopy showed that the nanoparticles were homogeneously distributed over the G@TLL surface with sizes of 53 nm and 165 nm. This G@TLL-Cu2O hybrid was successfully used in the degradation of toxic organic compounds such as trichloroethylene (TCE) and Rhodamine B (RhB). In the case of TCE, the hybrid presented a high catalytic capacity, degrading 60 ppm of product in 60 min in aqueous solution and room temperature without the formation of other toxic subproducts. In addition, a TOF value of 7.5 times higher than the unsupported counterpart (TLL-Cu2O) was obtained, demonstrating the improved catalytic efficiency of the system in the solid phase. The hybrid also presented an excellent catalytic performance for the degradation of Rhodamine B (RhB) obtaining a complete degradation (48 ppm) in 50 min in aqueous solution and room temperature and with the presence of a green oxidant as H2O2

Metal nanoparticles incorporated within graphene-enzyme preparations for synergistic multiactive catalysts

The development of catalytic systems with different chemo- and biocatalytic functionalities for sustainable one-pot multistep transformations represents a big challenge in modern chemistry. Here, we have designed and synthesized enzyme-metal hybrids’ materials of palladium and copper as multiactive heterogeneous catalysts. The in situ formation of metallic nanoparticles of different size and species on multilayer graphene-anchored Candida antarctica lipase (G@CALB) at room temperature and aqueous media allowed creation of different kinds of enzyme-metal nanoarchitectures, where the metal nanoparticles were synthesized exclusively when induced by an enzyme, dispersed homogeneously on the enzyme structure as the scaffold. The creation of copper or palladium nanoparticles on the graphene-enzyme preparation allowed obtaining a new type of enzyme-metal bifunctional catalyst conserving the enzymatic activity intact and enhancing the metallic properties. Furthermore, the creation of a CuPd alloy on immobilized enzyme preparation (G@CALB-PdNPs-CuNPs) allowed obtaining a new enzyme-bimetallic trifunctional catalyst, with extremely enhanced metallic activity by the synergistic effect. These hybrids were successfully applied in different cascade processes, where the hybrid G@CALB-PdNPs-CuNPs, based on its property, showed superior efficiency to bifunctional hybrids in the regioselective and asymmetric one-pot tandem processes tested.This work was supported by the Spanish National Research Council (CSIC) (projects PIE 201980E081 and MCIN/AEI/10.13039/501100011033, Project No. PID2019-106394GB-I00/AEI/10.13039/501100011033), and also by the Aragón-FSE Government (Spain, research group Aminoácidos y Péptidos E19_20R).Peer reviewe