Streptavidin-hosted organocatalytic aldol addition

In this report, the streptavidin-biotin technology was applied to enable organocatalytic aldol addition. By attaching pyrrolidine to the valeric motif of biotin and introducing it to streptavidin (Sav), a protein-based organocatalytic system was created, and the aldol addition of acetone with p-nitrobenzaldehyde was tested. The conversion of substrate to product can be as high as 93%. Although the observed enantioselectivity was only moderate (33:67 er), further protein engineering efforts can be included to improve the selectivity. These results have proven the concept that Sav can be used to host stereoselective aldol addition

Transfer hydrogenations catalyzed by streptavidin-hosted secondary amine organocatalysts

Here, the streptavidin–biotin technology was applied to enable organocatalytic transfer hydrogenation. By introducing a biotintethered pyrrolidine (1) to the tetrameric streptavidin (T-Sav), the resulting hybrid catalyst was able to mediate hydride transfer from dihydro-benzylnicotinamide (BNAH) to a,b-unsaturated aldehydes. Hydrogenation of cinnamaldehyde and some of its aryl-substituted analogues was found to be nearly quantitative. Kinetic measurements revealed that the T-Sav:1 assembly possesses enzyme-like behavior, whereas isotope effect analysis, performed by QM/MM simulations, illustrated that the step of hydride transfer is at least partially rate-limiting. These results have proven the concept that T-Sav can be used to host secondary amine-catalyzed transfer hydrogenations

Enabling protein-hosted organocatalytic transformations

In this review, the development of organocatalytic artificial enzymes will be discussed. This area of protein engineering research has underlying importance, as it enhances the biocompatibility of organocatalysis for applications in chemical and synthetic biology research whilst expanding the catalytic repertoire of enzymes. The approaches towards the preparation of organocatalytic artificial enzymes, techniques used to improve their performance (selectivity and reactivity) as well as examples of their applications are presented. Challenges and opportunities are also discussed

Biological Aspects, Advancements and Techno-Economical Evaluation of Biological Methanation for the Recycling and Valorization of CO2

Nowadays, sustainable and renewable energy production is a global priority. Over the past decade, several Power-to-X (PtX) technologies have been proposed to store and convert the surplus of renewable energies into chemical bonds of chemicals produced by different processes. CO2 is a major contributor to climate change, yet it is also an undervalued source of carbon that could be recycled and represents an opportunity to generate renewable energy. In this context, PtX technologies would allow for CO2 valorization into renewable fuels while reducing greenhouse gas (GHG) emissions. With this work we want to provide an up-to-date overview of biomethanation as a PtX technology by considering the biological aspects and the main parameters affecting its application and scalability at an industrial level. Particular attention will be paid to the concept of CO2-streams valorization and to the integration of the process with renewable energies. Aspects related to new promising technologies such as in situ, ex situ, hybrid biomethanation and the concept of underground methanation will be discussed, also in connection with recent application cases. Furthermore, the technical and economic feasibility will be critically analyzed to highlight current options and limitations for implementing a sustainable process

GaN-based power devices: Physics, reliability, and perspectives

Over the last decade, gallium nitride (GaN) has emerged as an excellent material for the fabrication of power devices. Among the semicon- ductors for which power devices are already available in the market, GaN has the widest energy gap, the largest critical field, and the highest saturation velocity, thus representing an excellent material for the fabrication of high-speed/high-voltage components. The presence of spon- taneous and piezoelectric polarization allows us to create a two-dimensional electron gas, with high mobility and large channel density, in the absence of any doping, thanks to the use of AlGaN/GaN heterostructures. This contributes to minimize resistive losses; at the same time, for GaN transistors, switching losses are very low, thanks to the small parasitic capacitances and switching charges. Device scaling and monolithic integration enable a high-frequency operation, with consequent advantages in terms of miniaturization. For high power/high- voltage operation, vertical device architectures are being proposed and investigated, and three-dimensional structures—fin-shaped, trench- structured, nanowire-based—are demonstrating great potential. Contrary to Si, GaN is a relatively young material: trapping and degradation processes must be understood and described in detail, with the aim of optimizing device stability and reliability. This Tutorial describes the physics, technology, and reliability of GaN-based power devices: in the first part of the article, starting from a discussion of the main proper- ties of the material, the characteristics of lateral and vertical GaN transistors are discussed in detail to provide guidance in this complex and interesting field. The second part of the paper focuses on trapping and reliability aspects: the physical origin of traps in GaN and the main degradation mechanisms are discussed in detail. The wide set of referenced papers and the insight into the most relevant aspects gives the reader a comprehensive overview on the present and next-generation GaN electronics

Association between preoperative evaluation with lung ultrasound and outcome in frail elderly patients undergoing orthopedic surgery for hip fractures: study protocol for an Italian multicenter observational prospective study (LUSHIP)

Hip fracture is one of the most common orthopedic causes of hospital admission in frail elderly patients. Hip fracture fixation in this class of patients is considered a high-risk procedure. Preoperative physical examination, plasma natriuretic peptide levels (BNP, Pro-BNP), and cardiovascular scoring systems (ASA-PS, RCRI, NSQIP-MICA) have all been demonstrated to underestimate the risk of postoperative complications. We designed a prospective multicenter observational study to assess whether preoperative lung ultrasound examination can predict better postoperative events thanks to the additional information they provide in the form of "indirect" and "direct" cardiac and pulmonary lung ultrasound signs

One-Stage Immediate Breast Reconstruction: A Concise Review

Background. One-stage direct-to-implant immediate breast reconstruction (IBR) is performed simultaneously with breast cancer resection. We explored indications, techniques, and outcomes of IBR to determine its feasibility, safety, and effectiveness. Material and Methods. We reviewed the available literature on one-stage direct-to-implant IBR, with or without acellular dermal matrix (ADM), synthetic mesh, or autologous fat grafting. We analyzed the indications, preoperative work-up, surgical technique, postoperative care, outcomes, and complications. Results. IBR is indicated for small-to-medium nonptotic breasts and contraindicated in patients who require or have undergone radiotherapy, due to unacceptably high complications rates. Only patients with thick, well-vascularized mastectomy flaps are IBR candidates. Expandable implants should be used for ptotic breasts, while anatomical shaped implants should be used to reconstruct small-to-medium nonptotic breasts. ADMs can be used to cover the implant during IBR and avoid muscle elevation, thereby minimizing postoperative pain. Flap necrosis, reoperation, and implant loss are more common with IBR than conventional two-staged reconstruction, but IBR has advantages such as lack of secondary surgery, faster recovery, and better quality of life. Conclusions. IBR has good outcomes and patient-satisfaction rates. With ADM use, a shift from conventional reconstruction to IBR has occurred. Drawbacks of IBR can be overcome by careful patient selection

Comparative biological evaluation of two new families of organometallic gold(I) complexes featuring N-heterocyclic carbene and alkynyl ligands

Experimental organometallic gold(I) compounds hold promise for anticancer therapy. This study reports the synthesis of two novel families of gold(I) complexes, including N1-substituted bis-N-heterocyclic carbene (NHCs) complexes of general formula [Au(N1-TBM)2]BF4 (N1-TBM = N1-substituted 9-methyltheobromin-8-ylidene) and mixed gold(I) NHC-alkynyl complexes, [Au(N1-TBM)alkynyl]. The compounds were fully characterised for their structure and stability in aqueous environment and in the presence of N-acetyl cysteine by nuclear magnetic resonance (NMR) spectroscopy. The structures of bis(1-ethyl-3,7,9-trimethylxanthin-8-ylidene)gold(I), (4-ethynylpyridine)(1,9-dimethyltheobromine-8-ylidene)gold(I) and of (2,8-Diethyl-10-(4-ethynylphenyl)-5,5-difluoro-1,3,7,9-tetramethyl-5H-4λ4,5λ4-dipyrrolo[1,2-c:2′,1′-f][1,3,2]diazaborinine)(1,3,7,9-tetramethylxanthin-8-ylidene)gold(I) were also confirmed by X-ray diffraction analysis. The compounds were studied for their properties as DNA G-quadruplexes (G4 s) stabilizers by fluorescence resonance energy transfer (FRET) DNA melting. Only the cationic [Au(N1-TBM)2]BF4 family showed moderate G4 stabilization properties with respect to the previously reported benchmark compound [Au(9-methylcaffein-8-ylidene)2]+ (AuTMX2). However, the compounds also showed marked selectivity for binding to G4 structures with respect to duplex DNA in competition experiments. For selected complexes, the interactions with G4 s were also confirmed by circular dichroism (CD) studies. Furthermore, the gold(I) complexes were assessed for their antiproliferative effects in human cancer cells in vitro, displaying moderate activity. Of note, among the mixed gold(I) NHC-alkynyl compounds, one features a fluorescent boron-dipyrromethene (BODIPY) moiety which allowed determining its uptake into the cytoplasm of cancer cells by fluorescence microscopy

The role of streptavidin and its variants in catalysis by biotinylated secondary amines

Here, we combine the use of host screening, protein crystallography and QM/MM molecular dynamics simulations to investigate how the protein structure affects iminium catalysis by biotinylated secondary amines in a model 1,4 conjugate addition reaction. Monomeric streptavidin (M-Sav) lacks a quaternary structure and the solvent-exposed reaction site resulted in poor product conversion in the model reaction with low enantio- and regioselectivities. These parameters were much improved when the tetrameric host T-Sav was used; indeed, residues at the symmetrical subunit interface were proven to be critical for catalysis through a mutagenesis study. The use of QM/MM simulations and the asymmetric dimeric variant D-Sav revealed that both Lys121 residues which are located in the hosting and neighboring subunits play a critical role in controlling the stereoselectivity and reactivity. Lastly, the D-Sav template, though providing a lower conversion than that of the symmetric tetrameric counterpart, is likely a better starting point for future protein engineering because each surrounding residue within the asymmetric scaffold can be refined for secondary amine catalysis