Dual-Mode Nanoprobes Based on Lanthanide Doped Fluoride Nanoparticles Functionalized by Aryl Diazonium Salts for Fluorescence and SERS Bioimaging.

The design of dual-mode fluorescence and Raman tags stimulates a growing interest in biomedical imaging and sensing applications as they offer the possibility to synergistically combine the versatility and velocity of fluorescence imaging with the specificity of Raman spectroscopy. Although lanthanide-doped fluoride nanoparticles (NPs) are among the most studied fluorescent nanoprobes, their use for the development of bimodal fluorescent-Raman probes has never been reported yet, to the best of the authors knowledge, probably due to the difficulty to functionalize them with Raman reporter groups. This gap is filled herein by proposing a fast and straightforward approach based on aryl diazonium salt chemistry to functionalize Eu3+ or Tb3+ doped CaF2 and LaF3 NPs by Raman scatters. The resulting surface-enhanced Raman spectroscopy (SERS)-encoded lanthanide-doped fluoride NPs retain their fluorescence labeling capacity and display efficient SERS activity for cell bioimaging. The potential of this new generation of bimodal nanoprobes is assessed through cell viability assays and intracellular fluorescence and Raman imaging, opening up unprecedented opportunities for biomedical applications.

Selective Nsp2 - and Csp2 - Photografting of Au-Surface by Aryldiazonium Salts and Arylazo Sulfonates.

Arylazo sulfonates (Ar-N=N-SO3 Na) have been found to undergo photografting on gold surface through both Au-Nsp2 - and Au-Csp2 - bond formation. The functionalized materials have been fully characterized by infrared reflection absorption spectroscopy (IRRAS), Raman, XPS, DFT calculations and UV-Vis absorption spectroscopy. These methods permit to evidence aromatic substituents (IRRAS), the Au-N=N signature (Raman and XPS spectroscopy), and the bond dissociation energy values of the two linkages (DFT calculation). The grafting proceeds through two competitive paths, namely a stepwise reaction involving an aryl radical (for the formation of the Au-Ar bonds) and a concerted reaction on the surface of gold (for Au-N=N-Ar bond formation). The occurrence of an aryl radical upon irradiation has been fully evidenced by EPR spectroscopy. Finally, E/Z photoisomerisation of the N=N bonds present on prepared few layer films has been observed by means of UV-Vis absorption spectroscopy.

Can the Realization of an External Wirsungostomy be an Option for High-Risk Pancreatic Anastomosis After Pancreaticoduodenectomy?

BACKGROUND: Clinically relevant postoperative pancreatic fistula (POPF) occurs in 15-20% of patients after pancreaticoduodenectomy (PD) and reintervention in the setting of Grade C POPF remains associated with a mortality rate of up to 25%. In patients at high risk of POPF, PD with external wirsungostomy (EW) could be a safe alternative that avoids pancreatico-enteric anastomosis while preserving the remnant pancreas. METHODS: Of the 155 consecutive patients who underwent PD from November 2015 to December 2020, 10 patients were managed using an EW, all with a fistula risk score (FRS) ≥ 7 and BMI ≥30 kg/m2, and/or major associated abdominal surgery. The pancreatic duct was cannulated with a polyethylene tube to allow good external drainage of the pancreatic fluid. We retrospectively analyzed postoperative complications and endocrine and exocrine insufficiencies. RESULTS: The median alternative FRS was 36.9% [22.1-45.2]. There was no postoperative death. The 90-day overall severe complication (grade ≥3) rate was 30% (n = 3 patients), no patient required reoperation, and 2 hospital readmissions occurred. 3 patients experienced Grade B POPF (30%), managed using image-guided drainage for 2 patients. The external pancreatic drain was removed after a median drainage time of 75 days [63-80]. Two patients presented with late symptoms (> 6 months) warranting interventional management (pancreaticojejunostomy and transgastric drainage). Six patients experienced significant weight loss (> 2 kg) 3 months after surgery. One year after surgery, 4 patients still complained of diarrhea and were treated with transit-delaying drugs. One patient presented new-onset diabetes one year after surgery, and 1 of the 4 patients with preexisting diabetes experienced worsening disease. CONCLUSION: EW after PD might be a solution to reduce post-operative mortality following PD in high-risk patients.

Examining the Role of Aryldiazonium Salts in Surface Electroinitiated Polymerization.

Historically, the irreversible reduction of aryldiazonium salts has provided a reliable method to modify surfaces, demonstrating a catalogue of suitable diazonium salts for targeted applications. This work expands the knowledge of diazonium salt chemistry to participate in surface electroinitiated emulsion polymerization (SEEP). The influence of concentration, electronic effects, and steric hindrance/regiochemistry of the diazonium salt initiator on the production of polymeric films is examined. The objective of this work is to determine if a polymer film can be tailored, controlling the thickness, density, and surface homogeneity using specific diazonium chemistry. The data presented herein demonstrate a significant difference in polymer films that can be achieved when selecting a variety of diazonium salts and vinylic monomers. A clear trend aligns with the electron-rich diazonium salt substitution providing the thickest films (up to 70.9 ± 17.8 nm) with increasing diazonium concentration and electron-withdrawing substitution achieving optimal homogeneity for the surface of the film at a 5 mM diazonium concentration.

Methodological and ethical quality of surgical trials from 2016 to 2020.

PURPOSE: Randomized controlled trials (RCTs) are the gold standard tool used to evaluate therapeutic interventions. The published results showed that progress still needs to be made not only from a methodological point of view but also from an ethical point of view. The aim of this study was to evaluate the methodological and ethical qualities of randomized clinical trials in surgery over the last few years. METHODS: All of the articles chosen for review reported on randomized controlled surgical trials and were published in 10 international journals between 2016 and 2020. Eligible studies were identified, selected, and then evaluated based on a broad set of predetermined criteria. Methodological quality was evaluated using the Jadad scale, and ethical quality was evaluated using the Berdeu score. RESULTS: The methodological quality score (Jadad scale) ranged from 5 to 13, with a mean of 10.0 ± 1.54. The methodological quality was insufficient (score ≤ 9) for 162 trials (31.2%). The ethical quality score ranged from 0.25 to 1, with a mean of 0.8 ± 0.11. Fifty-two articles (10%) did not state that informed consent was requested from the participants, and 21 articles (4%) did not report either research ethics committee or institutional committee protocol approval. CONCLUSION: The randomized clinical surgical trials analyzed showed that they had satisfactory methods in only 70% of the cases and that they had respected the fundamental ethical principles in 90% of the cases. However, less than 8% of the studies reported planned interim analysis, prospectively defined stopping rules, and independent monitoring committee.

Role of protective stoma after primary anastomosis for generalized peritonitis due to perforated diverticulitis-DIVERTI 2 (a prospective multicenter randomized trial): rationale and design (nct04604730).

BACKGROUND: Traditionally, patients with peritonitis Hinchey III and IV due to perforated diverticulitis were treated with Hartmann's procedure. In the past decade, resection and primary anastomosis have gained popularity over Hartmann's procedure and recent guidelines recommend Hartmann's procedure in two situations only: critically ill patients and in selected patients with multiple comorbidity (at high risk of complications). The protective stoma (PS) is recommended after resection with primary anastomosis, however its interest has never been studied. The aim of this trial is to define the role of systematic PS after resection and primary anastomosis for peritonitis Hinchey III and IV due to perforated diverticulitis. METHODS/DESIGN: This DIVERTI 2 trial is a multicenter, randomized, controlled, superiority trial comparing resection and primary anastomosis with (control group) or without (experimental group) PS in patients with peritonitis Hinchey III and IV due to perforated diverticulitis. Primary endpoint is the overall 1 year morbidity according to the Clavien-Dindo classification of surgical complications. All complications occurring during hospitalization will be collected. Late complications occurring after hospitalization will be collected during follow-up. In order to obtain 80% power for a difference given by respective main probabilities of 67% and 47% in the protective stoma and no protective stoma groups respectively, with a two-sided type I error of 5%, 96 patients will have to be included in each group, hence 192 patients overall. Expecting a 5% rate of patients not assessable for the primary end point (lost to follow-up), 204 patients will be enrolled. Secondary endpoints are postoperative mortality, unplanned reinterventions, incisional surgical site infection (SSI), organ/space SSI, wound disruption, anastomotic leak, operating time, length of hospital stay, stoma at 1 year after initial surgery, quality of life, costs and quality-adjusted life years (QALYs). DISCUSSION: The DIVERTI 2 trial is a prospective, multicenter, randomized, study to define the best strategy between PS and no PS in resection and primary anastomosis for patients presenting with peritonitis due to perforated diverticulitis. TRIAL REGISTRATION: ClinicalTrial.gov: NCT04604730 date of registration October 27, 2020. https://clinicaltrials.gov/ct2/show/NCT04604730?recrs=a&cond=Diverticulitis&draw=2&rank=12 .

Electrografting and Langmuir-Blodgett: Covalently Bound Nanometer-Thick Ordered Films on Graphite.

We present two different molecular organizations obtained from octadecylamine (ODA) molecules on a highly oriented pyrolytic graphite (HOPG) surface: (i) self-organized physisorbed ODA molecules lying flat on the surface and (ii) a strongly electrografted compact crystalline monolayer of ODA molecules standing up on the surface. This new structure is obtained by combining the Langmuir-Blodgett transfer of an ODA Langmuir film onto HOPG with oxidative electrografting. The presence of an organic film on HOPG is characterized by attenuated total reflectance-infrared spectroscopy and Raman spectroscopy, while atomic force microscopy and scanning tunneling microscopy allow the observation of the two molecular organizations with adsorbed molecules lying flat on HOPG or strongly grafted in an upright position on the HOPG surface. Interestingly, the second molecular organization preserves a hexagonal symmetry and its lattice parameters are intermediate between those of ODA Langmuir films and that of the HOPG underlying surface. The functionalization of surfaces with organic films is a major issue in the design of sensors with biomedical applications or organic electronics and energy storage devices and these structures may find applications in these fields.

Simultaneous Photografting of Two Organic Groups on a Gold Surface by using Arylazo Sulfones as Single Precursors.

Arylazo sulfones have been exploited as photoactivatable substrates for the simultaneous photografting of both aryl and methanesulfonyl groups on a gold surface. The obtained samples have been characterized by different spectroscopic techniques including ellipsometry and electrochemistry, infrared reflection absorption, surface-enhanced Raman spectroscopy, XPS, and AFM. Grafting occurs through a simple N-S cleavage and not, as usually observed with aromatic precursors, by electron transfer.

Expanding the Scope of Surface Grafted Polymers Using Electroinitiated Polymerization.

The ability to rapidly modify the surface of materials is a powerful means of tailoring interfaces and interphases for a variety of applications. In this work, we demonstrate the extensive scope of an electrochemically mediated surface modification technique, able to install a range of surface grafted polymers of varying polarity and functionality. The irreversible reduction of aryldiazonium salts initiates polymer growth and provides a "priming layer" for the polymers to attach to, covalently anchoring them to the surface. We show the broad applicability of this technique through polymerization of 19 acrylate monomers, as well as a noncarbonyl bearing monomer species, styrene. Surface bound films were characterized using FT-IR, ellipsometry, and water contact angle.

Alkyl-Modified Gold Surfaces: Characterization of the Au-C Bond.

The surface of gold can be modified with alkyl groups through a radical crossover reaction involving alkyliodides or bromides in the presence of a sterically hindered diazonium salt. In this paper, we characterize the Au-C(alkyl) bond by surface-enhanced Raman spectroscopy (SERS); the corresponding peak appears at 387 cm-1 close to the value obtained by theoretical modeling. The Au-C(alkyl) bond energy is also calculated, it reaches -36.9 kcal mol-1 similar to that of an Au-S-alkyl bond but also of an Au-C(aryl) bond. In agreement with the similar energies of Au-C(alkyl) and Au-S-(alkyl), we demonstrate experimentally that these groups can be exchanged on the surface of gold.

Surface functionalisation of polymers.

Many applications of polymers require the functionalisation of their surface for use in sensors, composite materials, membranes, microfluidic and biomedical devices and many others. Such surface modifications endow the surface with new properties independent of those of the bulk polymer. This tutorial review describes the different methods, based on very diverse principles, that are available to perform this surface functionalisation, including plasma and UV irradiation, atomic layer deposition, electrochemistry, oxidation, reduction, hydrolysis, the use of radicals and grafting "on" or "from" polymers. The principles of the different methods are briefly described and many examples are given to highlight the possibilities of the methods and the possible applications. A section is devoted to the surface modification of polymeric nanoparticles.

Some Theoretical and Experimental Insights on the Mechanistic Routes Leading to the Spontaneous Grafting of Gold Surfaces by Diazonium Salts.

The spontaneous grafting of diazonium salts on gold may involve the carbocation obtained by heterolytic dediazonation and not necessarily the radical, as usually observed on reducing surfaces. The mechanism is addressed on the basis of DFT calculations and experiments carried out under conditions where the carbocation and the radical are produced selectively. The calculations indicate that the driving force of the reaction leading from a gold cluster, used as a gold model surface, and the carbocation to the modified cluster is higher than that of the analogous reaction starting from the radical. The experiments performed under conditions of heterolytic dediazonation show the formation of thin films on the surface of gold. The grafting of a carbocation is therefore possible, but a mechanism where the cleavage of the Ar-N bond is catalyzed by the surface of gold cannot be excluded.

Efficient Covalent Modification of Multiwalled Carbon Nanotubes with Diazotized Dyes in Water at Room Temperature.

Tetrafluoroborate salts of diazotized Azure A (AA-N2+), Neutral Red (NR-N2+) and Congo Red (CR-N2+) dyes were prepared and reacted with multiwalled carbon nanotubes (MWCNTs) at room temperature, in water without any reducing agent. The as-modified MWCNTs were examined by IRATR, Raman spectroscopy, XPS, TGA, TEM, and cyclic voltammetry. The diazonium band located at ∼2350 cm-1 in the diazotized dye IR spectra vanished after attachment to the nanotubes whereas the Raman D/G peak ratio slightly increased after dye covalent attachment at a high initial diazonium/CNT mass ratio. XPS measurements show the loss of F 1s from the BF4- anion together with a clear change in the high-resolution C 1s region from the modified nanotubes. Thermogravimetric analyses proved substantial mass loadings of the organic grafts leveling off at 40.5, 34.3, and 50.7 wt % for AA, NR, and CR, respectively. High-resolution TEM pictures confirmed the presence of 1.5-7-nm-thick continuous amorphous layers on the nanotubes assigned to the aryl layers from the dyes. Cyclic voltammetry studies in acetonitrile (ACN) confirmed the grafting of the dyes; the latter retain their electrochemical behavior in the grafted state. The experimental results correlate remarkably well with quantum chemical calculations that indicate high binding energies between the dyes and the CNTs accounting for true covalent bonding (140-185 kJ/mol with the CNT-aryl distance <1.6 nm), though attachment by π stacking also contributes to obtaining stable hybrids. Finally, the pH-responsive character of the robust hybrids was demonstrated by a higher degree of protonation of Neutral Red-grafted CNTs at pH 2 compared to that of the neutral aqueous medium. This work demonstrates that diazotized dyes can be employed for the surface modification of MWCNTs in a very simple and efficient manner in water and at room temperature. The hybrids could be employed for many purposes such as optically pH-responsive materials, biosensors, and optothermal composite actuators to name a few.

Surface Modification of Polymers by Reaction of Alkyl Radicals.

The surfaces of poly(methyl methacrylate) and polyethylene are modified either (i) by a two-step process including the thermal reaction of alkyl radicals derived from bromohexanoic acid in a mixture of 2,6-dimethylbenzene diazonium salt and neat isopentyl nitrite at 60 °C, followed by reaction with p-nitroaniline, anthraquinone, neutral red, and polyethylene glycol moieties, or (ii) by reaction of a previously anthraquinone-modified bromohexanoic acid. The modified surfaces are characterized by IR, XPS, UV, and water contact angles. A mechanism is proposed to rationalize the results. This approach is an efficient way to modify and pattern polymer surfaces with different organic groups and chemical functionalities under mild conditions.

Reversible Trapping of Functional Molecules at Interfaces Using Diazonium Salts Chemistry.

Developing thin polymeric films for trapping, releasing, delivering, and sensing molecules is important for many applications in chemistry, biotechnology, and environment. Hence, a facile and scalable technique for loading specific molecules on surfaces would rapidly translate into applications. This work presents a novel method for the trapping of functional molecules at interfaces by exploiting diazonium salt chemistry. We demonstrate the efficiency of this approach by trapping two different molecules, 4-nitrobenzophenone and paracetamol, within polycarboxyphenyl layers grafted on gold and glassy carbon (GC) and by releasing them in acidic medium. The former molecule was chosen as a proof of concept for its electrochemical and spectroscopic properties, and the latter one was selected as an example of a pharmaceutical molecule. Advantages of the present approach rely on the simplicity, rapidity, and efficiency of the procedure for the reversible, on demand, trapping and release of functional molecules.

Surface Functionalization of Metals by Alkyl Chains through a Radical Crossover Reaction.

Alkyl chains are covalently attached onto metal surfaces by indirect reduction of the bromoalkyl derivative (RBr). This indirect reaction involves the formation (by spontaneous or electrochemical reduction of the 2,6-dimethylbenzenediazonium salt) of a sterically hindered aryl radical that abstracts a Br atom from RBr but does not react with the surface. This crossover reaction furnishes an alkyl radical that reacts with the surface. Starting from 6-bromohexanoic acid, carboxylic functionalized gold surfaces are prepared. "Layer-by-layer" assemblies are built from these surfaces and present some ionic selectivity.

Powerful Surface Chemistry Approach for the Grafting of Alkyl Multilayers on Aluminum Nanoparticles.

The synthesis of aluminum nanoparticles (Alnp) has raised promising perspectives these past few years for applications in energetic materials. However, because of their high reactivity, it is crucial to functionalize them before their use. In this work, we propose an original and simple chemical approach to graft spontaneously alkyl layers derived from alkyl halides at the surface of Alnp, by relying on the highly reductive character of these nanoparticles, when they are in the unoxidized form. Alnp were prepared in a glovebox and reacted with alkyl halides (RI and RBr) to give modified Alnp-R, as shown by infrared spectroscopy (IR), X-ray photoelectron spectroscopy (XPS), X-ray diffraction, thermogravimetric analysis (TGA), and microscopy. The coating is made of alkyl multilayers, which were found to be strongly anchored at the Alnp surface, as it resisted 2 h of rinsing in toluene. An electrocatalytic electron transfer promoted by Alnp is proposed to describe the mechanism of this grafting reaction.

One-step formation of bifunctionnal aryl/alkyl grafted films on conducting surfaces by the reduction of diazonium salts in the presence of alkyl iodides.

The formation of partial perfluoroalkyl or alkyl radicals from partial perfluoroalkyl or alkyl iodides (ICH2CH2C6F13 and IC6H13) and their reaction with surfaces takes place at low driving force (∼-0.5 V/SCE) when the electrochemical reaction is performed in acetonitrile in the presence of diazonium salts (ArN2(+)), at a potential where the latter is reduced. By comparison to the direct grafting of ICH2CH2C6F13, this corresponds to a gain of ∼2.1 V in the case of 4-nitrobenzenediazonium. Such electrochemical reaction permits the modification of gold surfaces (and also carbon, iron, and copper) with mixed aryl-alkyl groups (Ar = 3-CH3-C6H4, 4-NO2-C6H4, and 4-Br-C6H4, R = C6H13 or (CH2)2-C6F13). These strongly bonded mixed layers are characterized by IRRAS, XPS, ToF-SIMS, ellipsometry, water contact angles, and cyclic voltammetry. The relative proportions of grafted aryl and alkyl groups can be varied along with the relative concentrations of diazonium and iodide components in the grafting solution. The formation of the films is assigned to the reaction of aryl and alkyl radicals on the surface and on the first grafted layer. The former is obtained from the electrochemical reduction of the diazonium salt; the latter results from the abstraction of an iodine atom by the aryl radical. The mechanism involved in the growth of the film provides an example of complex surface radical chemistry.