Active coatings based on oxidized chitin nanocrystals and silk fibroins for the control of anthracnose in ‘Hass’ avocados
Funes, C. F.; Larach, A.; Besoain, X.; Serrano, D. D.; Hadad, C.; Pedreschi, R.; Van Nhien, A. N.; Fuentealba, C.
Int. J. Biol. Macromol. 2023, 253, 126673.
Postharvest avocado losses are mainly due to anthracnose disease caused by Colletotrichum gloeosporioides. Chemical fungicides are effective, but their negative effects on health and the environment have led to the search for sustainable alternatives such as biopolymer-based coatings and natural compounds. Therefore, chitin nanocrystals (NCChit) were extracted using a sustainable deep eutectic solvent (DES) and chemically modified into oxidized chitin nanocrystals (O-NCChit) or deacetylated chitin nanocrystals (D-NCChit) to modulate and increase the charge surface density and the dispersibility of the crystals. The modified NCChits were dispersed with silk fibroins (SF), essential oil (EO), melatonin (MT) and/or phenylalanine (Phe) to elaborate active coatings. Antioxidant and antifungal in vitro analyses showed that the O-NCChit/SF-based coating had the best performance. In addition, in vivo tests were carried out through the artificial inoculation of C. gloeosporioides on coated avocados. O-NCChit/SF/MT-based coatings reduced the severity of anthracnose by 45 %, the same effect as the chemical fungicide (Prochloraz®). Moreover, avocado quality parameters during cold storage and the shelf-life period were also evaluated, where nonsignificant differences were observed. Therefore, this study demonstrates the great potential of O-NCChit and SF in combination with active compounds for the control of anthracnose in ‘Hass’ avocados.
https://dx.doi.org/10.1016/j.ijbiomac.2023.126673

Revisiting organosolv strategies for sustainable extraction of valuable lignin: the CoffeeCat process
Vuillemin, M. E.; Quesada-Salas, M. C.; Hadad, C.; Jasniewski, J.; Husson, E.; Sarazin, C.
RSC Sustainability 2023.
An innovative and sustainable strategy for the selective extraction of lignin from lignocellulosic biomass has been designed, namely the CoffeeCat process, in which only green solvents and reagents are required: (i) water, (ii) 2-methyltetrahydrofuran-3-one (coffee furanone) recognized as a food grade ingredient and readily biodegradable and (iii) glutamic acid. Two fractions have been isolated from Miscanthus x giganteus, the delignified fraction (DL-glu) and the enriched-lignin fraction (L-glu). Competitive extraction yields of 27% and 43% of enriched-lignin fractions were respectively obtained at 140 °C (L-glu-140) and 180 °C (L-glu-180), based on the lignin content of the original biomass. The structural properties of these lignins were characterized by spectroscopic (FTIR and NMR), microscopic (SEM) and separative (SEC-MALLS) methods. Compared to other processes described in the literature, our strategy involved the isolation of lignin fractions with high purity (up to 84%). Both fractions have been valorized: (i) the DL-glu fractions have been subjected to ionic liquid pretreatment and subsequent enzymatic hydrolysis leading to a total depolymerization of the constitutive cellulose (99%) and to an efficient conversion of hemicellulose into xylose (70%); (ii) the L-glu fractions have been used to produce lignin nanoparticles (LNPs) in a mixture of 2-methyltetrahydrofuran-3-one/water (1/110 v/v). The size distribution (272 ± 9 nm and 472 ± 6 nm), charge (−29.2 ± 0.8 mV and −20.8 ± 0.4 mV) and regular spherical shape of these LNPs have been determined using Zetasizer-DLS measurements and SEM images of L-glu-140 and L-glu-180, respectively. In addition, the possibility of easy incorporation of the L-glu fraction into polylactic acid without requiring previous lignin modification has been preliminarily explored. The CoffeeCat process was thus demonstrated as a relevant eco-solution for an integrated lignocellulosic biorefinery.
https://dx.doi.org/10.1039/D3SU00050H

Theoretical and experimental studies of chitin nanocrystals treated with ionic liquid or deep eutectic solvent to afford nanochitosan sheets
Ferreira Funes, C.; Bouvier, B.; Cézard, C.; Fuentealba, C.; Jamali, A.; Courty, M.; Hadad, C.; Nguyen Van Nhien, A.
J. Mol. Liq. 2023, 375, 121350.
Chitin nanocrystals have gained growing interest due to their many excellent properties, however the higher crystallinity of these nano-rod-shaped particles is a major hindering factor in preparation of nanochitosans with low degree of acetylation (DA). Here we studied the effect of the ionic liquid 1-ethyl-3-methylimidazolium acetate (IL) and deep eutectic solvent (choline chloride:lactic acid) (DES) pretreatments of chitin nanocrystals (NCChits) before the deacetylation step using both experimental and theoretical approaches. The results showed that the ionic liquid pretreatment was able to partially disrupt the crystalline structure leading to a lower DA (18.2 %) after two cycles of deacetylation reaction. DES pretreatment, however, was unable to disturb the intra- and intermolecular hydrogen bonds, resulting in a DA of 73.6 % similar to that of unpretreated chitin nanocrystals (73.2 %). SEM images of chitin nanocrystals pretreated with ionic liquid showed that the crystals can rearrange into sheets. Molecular simulations reveal the detailed mechanism of chitin nanocrystal dissociation, in which the combination of a net molecular charge and hydrogen-bonding groups on a single scaffold (as is the case for [C2mim] and [OAc]) plays a paramount role. These results can open the way to afford controlled nanochitosan sheets from chitin nanocrystals.
https://dx.doi.org/10.1016/j.molliq.2023.121350

Copper-uptake mediated by an ecofriendly zwitterionic ionic liquid: A new challenge for a cleaner bioeconomy
Vuillemin, M. E.; Waterlot, C.; Verdin, A.; Laclef, S.; Cézard, C.; Lesur, D.; Sarazin, C.; Courcot, D.; Hadad, C.; Husson, E.; Van Nhien, A. N.
Journal of Environmental Sciences 2022.
This study aims to investigate the ability of an imidazolium biobased Zwitterionic Ionic Liquids (ZILs) in enhancing the phytoavailability of copper from garden (G) and vineyard (V) soils using the model plant ryegrass. Uncontaminated and artificially contaminated CuSO4 soils, unamended and ZIL-amended soil modalities were designed. The copper/ZIL molar ratio (1/4) introduced was rationally established based on molecular modeling and on the maximal copper concentration in artificially contaminated soil. Higher accumulation of copper in the shoots was detected for the uncontaminated and copper contaminated ZIL amended V soils (18.9 and 23.3 mg.kg−1, respectively) contrary to G soils together with a ZIL concentration of around 3% w/w detected by LC-MS analyses. These data evidenced a Cu-accumulation improvement of 38 and 66% compared to non-amended V soils (13.6 and 13.9 mg.kg−1 respectively). ZIL would be mainly present under Cu(II)-ZIL4 complexes in the shoots. The impact on the chemical composition of shoot were also studied. The results show that depending on the soils modalitity, the presence of free copper and/or ZIL led to different chemical compositions in lignin and monomeric sugar contents. In the biorefinery context, performances of enzymatic hydrolysis of shoots were also related to the presence of both ZIL and copper under free or complex forms. Ecotoxicity assessment of the vineyard soil samples indicated that the quantity of copper and ZIL remaining in the soils had no significant toxicity. ZIL amendment in a copper-contaminated soil was demonstrated as being a promising way to promote the valorization of phytoremediation plants.
https://dx.doi.org/10.1016/j.jes.2022.10.011

Fundamental insight into the interaction between a lithium salt and an inorganic filler for ion mobility using a synergic theoretical-experimental approach
Bidal, J.; CÉZard, C.; Bouvier, B.; Hadad, C.; Nguyen Van Nhien, A.; Becuwe, M.
J. Colloid Interface Sci. 2022.
The present paper aims at providing a fundamental insight into the interaction between a lithium salt and an inorganic filler in a perspective of lithium mobility. Through a synergistic approach, coupling experimental results and molecular dynamics simulations, the influence of the surface chemical state of the nanosilica Stöber-type on the dissociation of LiTFSI and its impact on the lithium conduction properties are studied. For this purpose, the surface modification of silica nanoparticles was performed by different methods such as calcination, lithiation and capping with organosilane. The impact of the surface modification on the dissociation of the lithium salt is further investigated by electrochemical impedance spectroscopy after impregnation of the material with a defined amount of lithium salt. The combined experimental and in silico analyses of the results, performed for the first time on such systems, allow a detailed understanding of the interaction between the salt and the support and should prove itself useful for the future design of hybrid polymer electrolytes in new generation batteries.
https://dx.doi.org/10.1016/j.jcis.2022.06.072

IL versus DES: Impact on chitin pretreatment to afford high quality and highly functionalizable chitosan
Huet, G.; Hadad, C.; González-Domínguez, J. M.; Courty, M.; Jamali, A.; Cailleu, D.; van Nhien, A. N.
Carbohydr. Polym. 2021, 269, 118332.
Chitin is mainly extracted from crustaceans, but this resource is seasonally dependent and can represent a major drawback to satisfy the traceability criterion for high valuable applications. Insect resources are valuable alternatives due to their lower mineral content. However, the deacetylation of chitin into chitosan is still an expensive process. Therefore, we herein compare the impact of both DES/IL-pretreatments on the efficiency of the chemical deacetylation of chitin carried out over two insect sources (Bombyx eri, BE and Hermetia illucens, HI) and shrimp shells (S). The results showed that chitosans obtained from IL-pretreated chitins from BE larva, present lower acetylation degrees (13–17%) than DES-pretreated samples (18–27%). A selective N-acylation reaction with oleic acid has also been performed on the purest and most deacetylated chitosans leading to high substitution degrees (up to 27%). The overall approach validates the proper chitin source and processing methodology to achieve high quality and highly functionalizable chitosan.
https://dx.doi.org/https://doi.org/10.1016/j.carbpol.2021.118332

Hybrid Electrolytes Based on Optimized Ionic Liquid Quantity Tethered on ZrO2 Nanoparticles for Solid-State Lithium-Ion Conduction
Bidal, J.; Becuwe, M.; Hadad, C.; Fleutot, B.; Davoisne, C.; Deschamps, M.; Porcheron, B.; Nhien, A. N. V.
ACS Appl. Mater. Interfaces 2021.
This paper describes the simple, highly reproducible, and robust synthesis of a new solid organic/inorganic electrolyte based on the ionic liquid (IL) 1-butyl-3-(carboxyundecyl)imidazolium bis(trifluoromethylsulfonyl)imide tethered to zirconia nanoparticles (15–25 nm) by coordination and named ZrO2@IL. The IL monolayer formation, ensured by two-dimensional solid-state NMR, at the nanoparticles’ surface considerably reduces both the IL’s consumption and the IL amount at the ZrO2 surface compared to the IL-based hybrid electrolytes reported in the literature. After LiTFSI, used as a lithium source, content optimization (26 wt %), the hybrid exhibits unprecedented stable conductivity passing from 0.6 × 10–4 S.cm–1 to 0.15 × 10–4 S.cm–1, respectively, from 85 °C to room temperature (25 °C). Unlike silica which is commonly adopted for this type of hybrid material, zirconia makes it possible to produce more impact-resistant pellets that are easier to compact, thus being favorable for accurate conductivity studies and battery development by electrode/composite/solid electrolyte layer stacking. The ZrO2@IL/LiTFSI solid hybrid electrolyte’s thermal stability (up to 300 °C) and performance make this electrolyte suitable for lithium conduction in all-solid-state batteries.
https://dx.doi.org/10.1021/acsami.0c22422

CHAPTER 4 Carbon Nanostructures and Polysaccharides for Biomedical Materials
González-Domínguez, J. M.; Álvarez-Sánchez, M. Á.; Hadad, C.; Benito, A. M.; Maser, W. K.
Carbon Nanostructures for Biomedical Applications 2021, 98-152.
Even though many members from the broad family of carbon nanostructures have been known to us for decades, and despite their promising potential in biology and medicine, there is still a long way ahead to reach the goal of using them in real applications. The cause of such a gap still lies in the persistent drawbacks of insolubility, processability difficulties, poor consistency of macroscopic assemblies and surface inertness of carbon nanostructures. However, solely their direct chemical derivatization might not solve the problem right away. New processing elements need to come into play, but this also twists the whole picture, as the toxicity and performance profiles become more complex. We herein analyse the potential of natural polysaccharides (with a particular focus on cellulose) towards hybrid materials and structures for biomedical purposes. The role that these biopolymers acquire when interfacing with carbon nanostructures goes far beyond a mere dispersing effect, but instead creates unprecedented synergies leading to hydrogels, aerogels, films or fibres with high biocompatibility and bioactivity. In this chapter, the history of carbon nanostructures and natural polysaccharides in the field of biomedical applications will be respectively reviewed, to subsequently go into detail of specific hybrids made with the most relevant biopolymers (namely cellulose, chitin, chitosan and alginate) with extraordinary prospects in biomedicine.
https://dx.doi.org/10.1039/9781839161070-00098

Graphene quantum dots: From efficient preparation to safe renal excretion
Hadad, C.; González-Domínguez, J. M.; Armelloni, S.; Mattinzoli, D.; Ikehata, M.; Istif, A.; Ostric, A.; Cellesi, F.; Alfieri, C. M.; Messa, P.; Ballesteros, B.; Da Ros, T.
Nano Research 2020.
Carbon nanomaterials offer excellent prospects as therapeutic agents, and among them, graphene quantum dots (GQDs) have gained considerable interest thanks to their aqueous solubility and intrinsic fluorescence, which enable their possible use in theranostic approaches, if their biocompatibility and favorable pharmacokinetic are confirmed. We prepared ultra-small GQDs using an alternative, reproducible, top-down synthesis starting from graphene oxide with a nearly 100% conversion. The materials were tested to assess their safety, demonstrating good biocompatibility and ability in passing the ultrafiltration barrier using an in vitro model. This leads to renal excretion without affecting the kidneys. Moreover, we studied the GQDs in vivo biodistribution confirming their efficient renal clearance, and we demonstrated that the internalization mechanism into podocytes is caveolae-mediated. Therefore, considering the reported characteristics, it appears possible to vehiculate compounds to kidneys by means of GQDs, overcoming problems related to lysosomal degradation.
https://dx.doi.org/10.1007/s12274-020-3096-y

New biobased-zwitterionic ionic liquids: efficiency and biocompatibility for the development of sustainable biorefinery processes
Huet, G.; Araya-Farias, M.; Alayoubi, R.; Laclef, S.; Bouvier, B.; Gosselin, I.; Cézard, C.; Roulard, R.; Courty, M.; Hadad, C.; Husson, E.; Sarazin, C.; Nguyen Van Nhien, A.
Green Chem. 2020, 22, 2935-2946.
A new family of biobased-zwitterionic ionic liquids (ZILs) have been synthesized starting from the renewable resource l-histidine natural amino acid and varying the lengths of the alkyl chains. These ZIL derivatives were firstly studied for their biocompatibility with different microorganisms including bacteria, molds and yeast. The obtained MIC values indicated that all the microorganisms were 5 to 25 times more tolerant to ZIL derivatives than the robust 1-ethyl-3-methylimidazolium acetate [C2mim][OAc] used as a reference. Modeling studies also revealed that the presence of the cation and the anion on the same skeleton together with the length of the N-alkyl chain would govern the biocompatibility of these neoteric solvents. Among the different synthesized ZILs, the N,N′-diethyl derivative has been demonstrated to be a suitable eco-alternative to the classically used [C2mim][OAc] for efficient pretreatment of harwood sawdust leading to a significant improvement of enzymatic saccharification. In addition, with up to a 5% w/v concentration in the culture medium, ZILs did not induce deleterious effects on fermentative yeast growth nor ethanol production.
https://dx.doi.org/10.1039/D0GC01002B

Conversion of Chitin in Ionic Liquids
Hadad, C.; Husson, E.; Van Nhien, A. N.
Encyclopedia of Ionic Liquids 2019, 1-6.
Present in the exoskeleton of arthropods or in the cell walls of fungi, chitin belongs to the most abundant polysaccharides after cellulose and is composed of linear chains of β-(1 → 4)- N-acetyl-D-glucosamine. There are three types of chitins (α-, β-, γ-chitin) with different crystallographic structures. Among them, α-chitin, the most prominent form, is arranged in an antiparallel fashion and is found in both crustacean and insects’ sources [ 21]. Despite its excellent biodegradability, biocompatibility, antimicrobial activity, nontoxicity, low immunogenicity, and good mechanical properties, chitin remains underutilized. This limitation in terms of application is mainly due to: (i) the low extraction efficiency, (ii) the extraction costs excessively high and not environmentally friendly, and (iii) the lack of solubility of this hydrophobic biopolymer. To overcome this weak solubility, pretreatments (chemical, mechanical, enzymatic, …) are interesting alternatives by...
https://dx.doi.org/10.1007/978-981-10-6739-6_80-1

Acidic Ionic Liquid as Both Solvent and Catalyst for Fast Chemical Esterification of Industrial Lignins: Performances and Regioselectivity
Husson, E.; Hulin, L.; Hadad, C.; Boughanmi, C.; Stevanovic, T.; Sarazin, C.
Frontiers in Chemistry 2019, 7.
Lignin can be considered an essential under-exploited polymer from lignocellulosic biomass representing a key for a profitable biorefinery. One method of lignin valorization could be the improvement of physico-chemical properties by esterification to enhance miscibility in apolar polyolefin matrices, thereby helping the production of bio-based composites. The present work describes for the first time a succeeded chemical esterification of industrial lignins with maleic anhydride in an acidic ionic liquid: 1-butyl-3-methyl imidazolium hydrogen sulfate without additional catalyst. This efficient strategy was applied to four industrial lignins: two softwood Kraft lignins (Indulin AT, Wayagamack), one hardwood Kraft lignin (Windsor), and one softwood organosolv lignin (Lignol), distinct in origin, extraction process and thus chemical structure. The chemical, structural, and thermal properties of modified lignins were characterized by ³¹P nuclear magnetic resonance, infrared spectroscopy and thermal analyses, then compared to those of unmodified lignins. After 4 h of reaction, between 30 to 52% of the constitutive hydroxyls were esterified depending on the type of lignin sample. The regioselectivity of the reaction was demonstrated to be preferentially orientated toward aliphatic hydroxyls for three out of four lignins (66.6, 65.5, and 83.6% for Indulin AT, Windsor and Lignol, respectively, vs. 51.7% for Wayagamack). The origin and the extraction process of the polymer would thus influence the efficiency and the regioselectivity of this reaction. Finally, we demonstrated that the covalent grafting of maleyl chain on lignins did not significantly affect thermal stability and increased significantly the solubility in polar and protic solvent probably due to additional exposed carboxylic groups resulted from mono-acylation independently of H/G/S ratio. Blending with polyolefins could then be considered in regard of compatibility with the obtained physico-chemical properties.
https://dx.doi.org/10.3389/fchem.2019.00578

Straightforward extraction and selective bioconversion of high purity chitin from Bombyx eri larva: Toward an integrated insect biorefinery
Huet, G.; Hadad, C.; Husson, E.; Laclef, S.; Lambertyn, V.; Araya Farias, M.; Jamali, A.; Courty, M.; Alayoubi, R.; Gosselin, I.; Sarazin, C.; Van Nhien, A. N.
Carbohydr. Polym. 2020, 228, 115382.
Chitins of different purity grades (45%, 89.7% and 93.3%) were efficiently extracted from Bombyx eri larva and fully physico-chemically characterized. Compared to commercially available and extracted α-chitin from shrimp shell, the collected data showed that insect chitins had similar characteristics in terms of crystallographic structures (α-chitin), thermal stability and degree of acetylation (>87%). The major differences lay in the crystallinity indexes (66% vs 75% for shrimp chitin) and in the morphological structures. Furthermore, low ash contents were determined for the insect chitins (1.90% vs 21.73% for shrimp chitin), making this chitin extraction and purification easier, which is highly valuable for an industrial application. Indeed, after only one step (deproteinization), the obtained chitin from Bombyx eri showed higher purity grade than the one extracted from shrimp shells under the same conditions. Insect chitins were then subjected to room temperature ionic liquid (RTIL) pretreatment prior to enzymatic degradation and presented a higher enzymatic digestibility compared to commercial one whatever their purity grade and would be thus a more relevant source for the selective production of N-acetyl-D-glucosamine (899.2 mg/g of chitin-2 steps vs 760 mg/g of chitin com). Moreover, for the first time, the fermentescibility of chitin hydrolysates was demonstrated with Scheffersomyces stipitis used as ethanologenic microorganism.
https://dx.doi.org/10.1016/j.carbpol.2019.115382

Synthesis of high molecular weight chitosan from chitin by mechanochemistry and aging
Di Nardo, T.; Hadad, C.; Nguyen Van Nhien, A.; Moores, A.
Green Chem. 2019.
Chitosan can be obtained from the deacetylation of chitin. This process is however difficult and usually accompanied by depolymerization, affording low molecular weight chitosan. We report a novel path, relying on the combination of mechanochemistry and aging, to yield high molecular weight chitosan with minimal use of energy and solvent. This method is versatile and applicable to a number of chitin sources, including crude crustacean and insect shells, yielding deacetylation up to 98% and remarkably high molecular weights. Chitin deacetylation was studied by magic angle spinning nuclear magnetic resonance and molecular weight was estimated by viscometry. This process affords chitosan in a safer fashion and with less materials and energy usage compared to the classic hydrothermal one.
http://dx.doi.org/10.1039/C9GC00304E

The effect of room temperature ionic liquids on the selective biocatalytic hydrolysis of chitin via sequential or simultaneous strategies
Husson, E.; Hadad, C.; Huet, G.; Laclef, S.; Lesur, D.; Lambertyn, V.; Jamali, A.; Gottis, S.; Sarazin, C.; Nguyen Van Nhien, A.
Green Chem. 2017, 19, 4122-4131.
An efficient conversion of chitin, the second most abundant renewable polymer on the Earth, into N-acetylglucosamine and N,N[prime or minute]-diacetylchitobiose, using room temperature ionic liquids (RTILs) and commercially available chitinases is described for the first time. The sequential strategy consists of the use of RTILs to pretreat chitin under mild conditions as a first step before enzymatic hydrolysis. [C2mim][OAc] (1-ethyl-3-methyl imidazolium) pretreatment provides an efficient production of N-acetylglucosamine (185.0 +/- 4.0 mg per g chitin) or N,N[prime or minute]-diacetylchitobiose (667.60 +/- 20.71 mg per g chitin) catalyzed by chitinase from Trichoderma viride or Streptomyces griseus, respectively. A thorough investigation of the structural changes of chitin induced by RTIL pretreatment suggested an increase in enzymes' accessibility to the chitin substrate. Alternatively, a one-pot enzymatic hydrolysis of chitin in [C2mim][OAc]-aqueous medium constitutes a promising simultaneous route to selectively generate N-acetylglucosamine or N,N[prime or minute]-diacetylchitobiose by decreasing the required [C2mim][OAc] amount and the number of steps. Finally, the combination of the two chitinases from T. viride and S. griseus was shown to be very relevant to considerably increase the production of N-acetylglucosamine up to 760.0 +/- 0.1 mg per g chitin.
http://dx.doi.org/10.1039/c7gc01471f

Nanocrystalline cellulose-fullerene: Novel conjugates
Herreros-López, A.; Carini, M.; Da Ros, T.; Carofiglio, T.; Marega, C.; La Parola, V.; Rapozzi, V.; Xodo, L. E.; Alshatwi, A. A.; Hadad, C.; Prato, M.
Carbohydr. Polym. 2017, 164, 92-101.
The covalent grafting of two amino-fullerene C60 derivatives (C60-LC-NH2 and C60-SC-NH2, LC = long chain and SC = short chain) onto the surface of TEMPO oxidized nanocrystalline cellulose (NCC-COOH) has been reported for the first time. These hybrids (NCC-LC-C60 and NCC-SC-C60) form stable colloidal suspensions at concentrations up to 0.5 mg/mL and act as effective photosensitizers for singlet oxygen production as demonstrated by the oxidation of L-methionine-methyl ester to the corresponding sulphoxide. Using the same approach, in a one-pot reaction both a fluorescent target molecule (FITC-LC-NH2) and the C60-LC-NH2 derivative have been successfully attached covalently onto the NCC-COOH surface. These hybrids, which showed no cytotoxicity on MCF-7 human breast cancer cells could be good candidates in photodynamic cancer therapy.
http://dx.doi.org/10.1016/j.carbpol.2017.01.068

Triazine-Carbon Nanotubes: New Platforms for the Design of Flavin Receptors
Lucio, M. I.; Pichler, F.; Ramirez, J. R.; de la Hoz, A.; Sanchez-Migallon, A.; Hadad, C.; Quintana, M.; Giulani, A.; Bracamonte, M. V.; Fierro, J. L. G.; Tavagnacco, C.; Herrero, M. A.; Prato, M.; Vazquez, E.
Chem. - Eur. J. 2016, 22, 8879-8888.
The synthesis of functionalized carbon nanotubes as receptors for riboflavin (RBF) is reported. Carbon nanotubes, both single-walled and multi-walled, have been functionalized with 1,3,5-triazines and p-tolyl chains by aryl radical addn. under microwave irradn. and the derivs. have been fully characterized by using a range of techniques. The interactions between riboflavin and the hybrids were analyzed by using fluorescence and UV/Vis spectroscopic techniques. The results show that the attached functional groups minimize the π-π stacking interactions between riboflavin and the nanotube walls. Comparison of p-tolyl groups with the triazine groups shows that the latter have stronger interactions with riboflavin because of the presence of hydrogen bonds. Moreover, the triazine derivs. follow the Stern-Volmer relationship and show a high assocn. const. with riboflavin. In this way, artificial receptors in catalytic processes could be designed through specific control of the interaction between functionalized carbon nanotubes and riboflavin. [on SciFinder(R)]
http://dx.doi.org/10.1002/chem.201600630

Synthesis and Catalytic Activity of Gold Nanoparticles Supported on Dendrimeric Nanocellulose Hybrids
Herreros-Lopez, A.; Hadad, C.; Yate, L.; Alshatwi, A. A.; Vicentini, N.; Carofiglio, T.; Prato, M.
Eur. J. Org. Chem. 2016, 2016, 3186-3192.
Thanks to their unique properties, such as (i) renewability, (ii) high aspect ratios, (iii) low d., (iv) biodegradability, (v) high strength, and (vi) stiffness, there have been many reports in recent years detailing the isolation and functionalization of cellulose nanowhiskers from cellulose. Moreover, nanocellulose can be produced in large quantities in a cost-effective manner and can be easily functionalized due to its high d. of hydroxy groups. In the present work, alkynyl-dendrons of the PAMAM family were covalently attached to azide-functionalized cellulose nanocrystals by click chem. (Huisgen cycloaddn.). The resulting cycloadducts were then used as templates for the prepn. of stable and monodispersed gold nanoparticles in aq. media. The catalytic capabilities of these hybrid materials were studied in the sodium borohydride mediated redn. of 4-nitrophenol to 4-aminophenol, which served as a model reaction. [on SciFinder(R)]
http://dx.doi.org/10.1002/ejoc.201600148

In vitro and in vivo characterization of graphene oxide coated porcine bone granules
Ettorre, V.; De Marco, P.; Zara, S.; Perrotti, V.; Scarano, A.; Di Crescenzo, A.; Petrini, M.; Hadad, C.; Bosco, D.; Zavan, B.; Valbonetti, L.; Spoto, G.; Iezzi, G.; Piattelli, A.; Cataldi, A.; Fontana, A.
Carbon 2016, 103, 291-298.
Graphene oxide (GO) demonstrated to improve the wound healing properties of materials intended for bone replacement. The main objective of this study was the setting up of a simple and effective procedure for the prodn. of GO-coated porcine bone (PB) granules and the characterization of the obtained material in order to improve its properties by exploiting chem., phys., biol. and mech. features that the GO coating could confer to pre-formed PB granules. The obtained coating was homogeneously distributed on PB granule surface and demonstrated to confer PB an increased resistance to fracture load. Biol. analyses evidenced no toxic effects of GO-coated PB samples on primary human gingival fibroblasts, and no inflammatory response around the grafted particles when implanted in vivo on a sheep model although GO-coated PB samples did not appear to improve new bone formation efficacy compared with the control within the investigated time. A small loss of GO was however detected, indicating the opportunity to investigate less GO concd. samples. In conclusion, this study presents a novel and low cost approach to the development of functionalized biomimetic hybrid materials which can be applied to other bone substitute materials in order to improve their performances. [on SciFinder(R)]
http://dx.doi.org/10.1016/j.carbon.2016.03.010

Intracellular degradation of chemically functionalized carbon nanotubes using a long-term primary microglial culture model
Bussy, C.; Hadad, C.; Prato, M.; Bianco, A.; Kostarelos, K.
Nanoscale 2016, 8, 590-601.
Chem. functionalized carbon nanotubes (f-CNTs) have been used in proof-of-concept studies to alleviate debilitating neurol. conditions. Previous in vivo observations in brain tissue have suggested that microglia - acting as resident macrophages of the brain - play a crit. role in the internalization of f-CNTs and their partial in situ biodegrdn. following a stereotactic administration in the cortex. At the same time, several reports have indicated that immune cells such as neutrophils, eosinophils and even macrophages could participate in the processing of carbon nanomaterials via oxidn. processes leading to degrdn., with surface properties acting as modulators of CNT biodegradability. In this study we questioned whether degradability of f-CNTs within microglia could be modulated depending on the type of surface functionalization used. We investigated the kinetics of degrdn. of multi-walled carbon nanotubes (MWNTs) functionalized via different chem. strategies that were internalized within isolated primary microglia over three months. A cellular model of rat primary microglia that can be maintained in cell culture for a long period of time was first developed. The Raman structural signature of the internalized f-CNTs was then studied directly in cells over a period of up to three months, following a single exposure to a non-cytotoxic concn. of three different f-CNTs (carboxylated, aminated and both carboxylated and aminated). Structural modifications suggesting partial but continuous degrdn. were obsd. for all nanotubes irresp. of their surface functionalization. Carboxylation was shown to promote more pronounced structural changes inside microglia over the first two weeks of the study. [on SciFinder(R)]
http://dx.doi.org/10.1039/C5NR06625E

Liposome-induced exfoliation of graphite to few-layer graphene dispersion with antibacterial activity
Zappacosta, R.; Di Giulio, M.; Ettorre, V.; Bosco, D.; Hadad, C.; Siani, G.; Di Bartolomeo, S.; Cataldi, A.; Cellini, L.; Fontana, A.
J. Mater. Chem. B 2015, 3, 6520-6527.
Few-layer graphene aq. dispersions are obtained by exploiting liposomes as effective exfoliating agents for graphite. Raman measurements evidence the presence of non-oxidized double layer graphene as well as amphiphilic phospholipid mols. organized in bilayers in the samples. TEM analyses confirmed that the obtained homogeneous graphene nanosheets are embedded in the liposomal bilayer. The as-prepd. graphene aq. dispersion is stable for days and demonstrates significant antibacterial activity against both Gram-pos. (Staphylococcus aureus) and Gram-neg. (Escherichia coli) strains, with a redn. in the growth of S. aureus and E. coli as high as 60 and 78%, resp. [on SciFinder(R)]
http://dx.doi.org/10.1039/C5TB00798D

Chemical modification of carbon nanomaterials (SWCNTs, DWCNTs, MWCNTs and SWCNHs) with diphenyl dichalcogenides
Syrgiannis, Z.; Bonasera, A.; Tenori, E.; La Parola, V.; Hadad, C.; Gruttadauria, M.; Giacalone, F.; Prato, M.
Nanoscale 2015, 7, 6007-6013.
Control over chem. functionalization is a crucial point in the field of nanotechnol. Herein, we present the covalent functionalization of several carbon nanoforms (single-walled carbon nanotubes, double-walled carbon nanotubes, multi-walled carbon nanotubes and carbon nanohorns) by means of di-Ph dichalcogenides. These ones show different reactivity to the nanomaterials and are able to modify their electronic properties depending on the electronegativity of the functionalizing heteroatom. Theor. calcns. were also performed to support the exptl. results. All the modified structured nanocarbons were thoroughly characterized by TGA Raman, XPS, UV/Vis/nIR, IR and TEM techniques. Our findings propose a simple approach to functionalize carbon nanomaterials and, in the meantime, to tune their electronic properties. [on SciFinder(R)]
http://dx.doi.org/10.1039/C4NR07196D

Synthesis and anti-HIV activity of carboxylated and drug-conjugated multi-walled carbon nanotubes
Iannazzo, D.; Pistone, A.; Galvagno, S.; Ferro, S.; De Luca, L.; Monforte, A. M.; Da Ros, T.; Hadad, C.; Prato, M.; Pannecouque, C.
Carbon 2015, 82, 548-561.
Carbon nanotubes have attracted particular attention in antiviral therapy and recently were explored as HIV inhibitors through structure-based design. In order to prove their in vitro ability to interact with viral enzymes and to act as HIV inhibitors, the authors have studied the antiviral potentiality of highly hydrophilic and dispersible carboxylated multi-walled carbon nanotubes (ox-MWCNT) and the activity exerted by the same nanomaterial bearing antiretroviral drugs and hydrophilic functionalities. The antiretroviral drugs chosen for this study were 2 newly synthesized benzimidazolones, CHI360 and CHI415, belonging to a series of active non-nucleoside reverse transcriptase inhibitors (RTI), and lamivudine (3TC), a known antiretroviral nucleoside agent, currently used in anti-HIV therapy. From this study, the physicochem. properties of these nanomaterials, namely hydrophilicity and dispersibility, emerged as the most relevant features able to control the antiviral activity. The more hydrophilic and dispersible oxidized samples, ox-MWCNT and MWCNT-C-CHI360, showed the best results with IC50 values of 11.43 μg/mL and 4.56 μg/mL, resp. [on SciFinder(R)]
http://dx.doi.org/10.1016/j.carbon.2014.11.007

Efficient Microwave-Assisted Synthesis of PCBM Methanofullerenes (C60 and C70)
Hadad, C.; Syrgiannis, Z.; Bonasera, A.; Prato, M.
Eur. J. Org. Chem. 2015, 2015, 1423-1427.
PCBM is a fullerene deriv. (phenyl-C61-butyric acid Me ester) considered to be one of the best n-type org. semiconductors and plays a relevant role in org. photovoltaic solar cells. Much effort has been devoted to the optimization of the synthesis of PCBM's. PC61BM and PC71BM fullerene mono-adducts but also PCBM-like derivs. are successfully prepd. by a one-step cyclopropanation reaction under microwave irradn. The products were collected in good yields in short time, during which isomerization of the open [5,6] to the closed [6,6] form takes place in situ. In addn., with the use of two cycles of irradn., a series of mixts. of bis-adduct PCBM-like derivs. were also obtained in good yields. [on SciFinder(R)]
http://dx.doi.org/10.1002/ejoc.201403563

Multipurpose Nature of Rapid Covalent Functionalization on Carbon Nanotubes
Gonzalez-Dominguez, J. M.; Santidrian, A.; Criado, A.; Hadad, C.; Kalbac, M.; Da Ros, T.
Chem. - Eur. J. 2015, 21, 18631-18641.
In the vast field of functionalization routes to carbon nanoforms, the fulfillment of such crit. requirements as quick and nonharsh methods, good dispersibility, introduction of reactive groups, short reaction time, and low cost can be quite challenging. Traditional thermally induced diazonium chem. on single-walled carbon nanotubes (SWCNTs) is revisited by using com. anilines and providing useful insight into the versatility of this approach. Functionalized SWCNTs with multiple controllable features, such as degree (and ratio) of coverage, orthogonalization, doping, and high water dispersibility, are obtained by introducing benzenesulfonic acid and benzylamine moieties. The scenario opens up an avenue to address relevant applications in which most functionalization methods could not be applied in a straightforward way. [on SciFinder(R)]
http://dx.doi.org/10.1002/chem.201503085