Correction: Flavin-adenine-dinucleotide gold complex nanoparticles: chemical modeling design, physico-chemical assessment and perspectives in nanomedicine.

[This corrects the article DOI: 10.1039/D1NA00444A.].

Correction to "Idarubicin-Gold Complex: From Crystal Growth to Gold Nanoparticles".

[This corrects the article DOI: 10.1021/acsomega.0c04501.].

Idarubicin-Gold Complex: From Crystal Growth to Gold Nanoparticles.

Idarubicin (IDA) is the analog of daunorubicin (DNR). The absence of the methoxy group at position 4 of IDA remarkably improved lipophilicity, which is responsible for extra cellular uptake, higher DNA-binding ability, and considerable cytotoxicity in correlation with doxorubicin (DOX) and DNR. In this paper, we conceived two principal objectives: we realized the crystal structure of IDA by X-ray diffraction measurements on single crystals at room temperature (monoclinic, space group P21, a = 5.1302(2) Å, b = 9.9122(5) Å, c = 24.8868(11) Å; ß = 91.425(4)°; V = 1265.14(10) Å3) with refinements of the structure converged to the final R = 3.87%. The second objective has been to develop gold nanoparticles encapsulated with idarubicin through an original methodology in which gold salt (HAuCl4) is chelated with IDA and diacid polymer (PEG) to form hybrid nanoparticles called IDA IN PEG-AuNPs in which drug solubility was enhanced. The computational studies were in agreement with the experimental observations. These hybrid nanoparticles and their precursors were analyzed by Raman, UV-Vis, 1H NMR, and transmission electron microscopy (TEM). The main results are completed by a theoretical approach to understand the whole process.

Flavin-adenine-dinucleotide gold complex nanoparticles: chemical modeling design, physico-chemical assessment and perspectives in nanomedicine.

Flavoproteins play an important role in the regulatory process of cell life, and they are involved in several redox reactions that regulate the metabolism of carbohydrates, amino acids, and lipids. The development of effective drug delivery systems is one of the major challenges in the fight against cancer. This study involves a nanomedicine pathway to encapsulate the cofactor flavin adenine dinucleotide (FAD) using polymeric gold nanoparticles (PEG-AuNPs) through two chemical methods of functionalization (chelation (IN); carbodiimide chemistry (ON)). These hybrid gold nanoparticles and their precursors were characterized by analytical techniques (Raman, UV-Vis, and H1-NMR spectroscopy and transmission electron microscopy (TEM)) which confirmed the grafting of the cofactor agent. The results of the computational studies (Density Functional Theory (DFT)) were in agreement with the experimental observations. We also monitored the interaction of our hybrid nanoparticle systems with small aptamers (APT) in order to validate the hypotheses on the biomolecular mechanisms and also investigate their biological efficiency on pancreatic cancer cells (MIAPaCa-2 cells).

Experimental and theoretical studies of the inclusion complex of different linear aliphatic alcohols with cyclodextrins.

Cyclodextrins are supramolecules widely used to help solubilization of hydrophobic molecules via host: guest complexation. To prepare the complexes, co-solvents like alcohols are mandatory and play an important role in the complexation process. In particular, the length of the aliphatic chain in primary linear alcohol can help the preparation and the stability of such complexes. The inclusion complexes of different linear aliphatic alcohols with beta cyclodextrin (ßCD) were prepared. The resultant complexes were analyzed in solution by proton nuclear magnetic resonance spectroscopy (1H NMR) and in the solid state by Differential Scanning Calorimetry (DSC) and powder X-ray diffraction (PXRD). Specific complexes are obtained in presence of alcohols longer than hexanol while the shorter alcohols act as a molecule of water solvent. Computations of energetic and thermodynamic properties followed by predictions of the more stable molecular structures for inclusion complexes by molecular modelling are in accordance with the experimental results.

Investigation of aromatic hydrocarbon inclusion into cyclodextrins by Raman spectroscopy and thermal analysis.

Among various cavitand molecules, cyclodextrins are extensively studied due to their ability to form host-guest complexes with small hydrophobic molecules. Aiming to explore cyclodextrin implementation on the scopes related to the environmental pollution monitoring or remediation, extensive studies for understanding the cyclodextrin-based host-guest complex formation with selected targeted substances are conducted. In this context, two polycyclic aromatic hydrocarbons, naphthalene and fluoranthene as well as toluene as a member of volatile organic compounds, were studied regarding their ability to encapsulate into cyclodextrin cavities. Synthesised complexes were examined by thermogravimetric analysis combined with Raman spectroscopy. The obtained results demonstrated that the size between targeted molecules and the cyclodextrin cavities strongly correlates with its ability to engage in complexation. Thus, this latter parameter plays an important role in the inclusion complex formation as well as in the strength of the interaction between the molecules.

Tunable Design of Gold(III)-Doxorubicin Complex-PEGylated Nanocarrier. The Golden Doxorubicin for Oncological Applications.

To date, the translation of Au (III) complexes into chemotherapeutic agents has been hindered by their low stability under physiological conditions, a crucial parameter in drug development. In this study, we report an innovative four-step synthesis of a stable Au (III)-doxorubicin (DOX) complex, acting as a key constitutive component of doxorubicin-loaded PEG-coated nanoparticles (DOX IN-PEG-AuNPs). For therapeutic purposes, such AuNPs were then functionalized with the anti-Kv11.1 polyclonal antibody (pAb), which specifically recognizes the hERG1 channel that is overexpressed on the membrane of human pancreatic cancer cells. The nature of the interactions between DOX and Au (III) ions was probed by various analytical techniques (Raman spectroscopy, UV-vis, and (1)H NMR), which enabled studying the Au (III)-DOX interactions during AuNPs formation. The theoretical characterization of the vibrational bands and the electronic transitions of the Au (III)-DOX complex calculated through computational studies showed significant qualitative agreement with the experimental observations on AuNPs samples. Stability in physiological conditions and efficient drug loading (up to to 85 w/w %) were achieved, while drug release was strongly dependent on the structure of DOX IN-PEG-AuNPs and on the pH. Furthermore, the interactions among DOX, PEG, and Au (III) ions in DOX IN-PEG-AuNPs differed significantly from those found in polymer-modified AuNPs loaded with DOX by covalent linkage, referred to as DOX ON-PEG-AuNPs. In vitro experiments indeed demonstrated that such differences strongly influenced the therapeutic potential of AuNPs in pancreatic cancer treatment, with a significant increase of the DOX therapeutic index when complexed to Au (III) ions. Collectively, our study demonstrated that Au (III)-DOX complexes as building blocks of PEGylated AuNPs constitutes a promising approach to transform promising Au (III) complexes into real chemotherapeutic drugs for the treatment of pancreatic cancer.

Aging of monolithic zirconia dental prostheses: Protocol for a 5-year prospective clinical study using ex vivo analyses.

BACKGROUND: Recent introduction of computer-aided design/computer-aided manufacturing (CAD/CAM) monolithic zirconia dental prostheses raises the issue of material low thermal degradation (LTD), a well-known problem with zirconia hip prostheses. This phenomenon could be accentuated by masticatory mechanical stress. Until now zirconia LTD process has only been studied in vitro. This work introduces an original protocol to evaluate LTD process of monolithic zirconia prostheses in the oral environment and to study their general clinical behavior, notably in terms of wear. METHODS/DESIGN: 101 posterior monolithic zirconia tooth elements (molars and premolars) are included in a 5-year prospective clinical trial. On each element, several areas between 1 and 2 mm2 (6 on molars, 4 on premolars) are determined on restoration surface: areas submitted or non-submitted to mastication mechanical stress, glazed or non-glazed. Before prosthesis placement, ex vivo analyses regarding LTD and wear are performed using Raman spectroscopy, SEM imagery and 3D laser profilometry. After placement, restorations are clinically evaluated following criteria of the World Dental Federation (FDI), complemented by the analysis of fracture clinical risk factors. Two independent examiners perform the evaluations. Clinical evaluation and ex vivo analyses are carried out after 6 months and then each year for up to 5 years. DISCUSSION: For clinicians and patients, the results of this trial will justify the use of monolithic zirconia restorations in dental practice. For researchers, the originality of a clinical study including ex vivo analyses of material aging will provide important data regarding zirconia properties.Trial registration: ClinicalTrials.gov Identifier: NCT02150226.

In silico studies, synthesis and binding evaluation of substituted 2-pyrrolidinones as peptidomimetics of RGD tripeptide sequence.

In silico optimisation, synthesis and binding evaluation of αvß3 integrin's affinity for precursors of a new RGD peptidomimetics family are presented. The 2-pyrrolidinone building block was obtained by condensation of l-lysine with dimethoxydihydrofuran followed by reduction. The ring was functionalized with a carboxylic acid and a guanidinium appendage. On the pyrrolidinone heterocycle, the effects on affinity of position, length and relative geometry of the two acid or basic functionalized side chains introduced on the pyrrolidinone ring have been previously evaluated by docking studies. Peptidomimetics have finally been evaluated by competition binding assays for αvß3 integrin's affinity using radio-ligands.

Complexes with redox-active ligands: synthesis, structure, and electrochemical and photophysical behavior of the Ru(II) complex with TTF-annulated phenanthroline.

Ru(II) complexes with chelating ligands, 4',5'-ethylenedithiotetrathiafulvenyl[4,5-f][1,10]phenanthroline (L1), 1,3-dithiole-2-thiono[4,5-f][1,10]phenanthroline (L2), and 1,3-dithiole-2-ono[4,5-f][1,10]phenanthroline (L3), have been prepared and their structural, electrochemical, and photophysical properties investigated. Density functional theory (DFT) calculations indicate that the highest occupied molecular orbital of [Ru(bpy)2(L1)](PF6)2 (1) is located on the tetrathiafulvalene (TTF) subunit and appears ~0.6 eV above the three Ru-centered d orbitals. In agreement with this finding, 1 exhibits three reversible oxidations: the two at lower potentials take place on the TTF subunit, and the one at higher potential is due to the Ru(3+)/Ru(2+) redox couple. Complexes [Ru(bpy)2(L2)](PF6)2 (2) and [Ru(bpy)2(L3)](PF6)2 (3) exhibit only the Ru(3+)/Ru(2+)-related oxidation. The optical absorption spectra of all complexes reveal a characteristic metal-to-ligand charge transfer (MLCT) band centered around 450 nm. In addition, in the spectrum of 1 the MLCT band is augmented by a low-energy tail that extends beyond 500 nm and is attributed to the intraligand charge transfer (ILCT) transition of L1, according to time-dependent DFT calculations. The substantial decrease in the luminescence quantum yield of 1 compared to those of 2 and 3 is attributed to the reductive quenching of the emissive state via electron transfer from the TTF subunit to the Ru(3+) center, thus allowing nonradiative relaxation to the ground state through the lower-lying ILCT state. In the presence of O2, complex 1 undergoes a photoinduced oxidative cleavage of the central C═C bond of the TTF fragment, resulting in complete transformation to 3. This photodegradation process was studied with (13)C NMR and optical absorption spectroscopy.

Tetrathiafulvalene-1,3,5-triazines as (multi)donor-acceptor systems with tunable charge transfer: structural, photophysical, and theoretical investigations.

Palladium-catalyzed cross-coupling reactions between chlorinated 1,3,5-triazines (TZ) and tetrathiafulvalene (TTF) trimethyltin derivatives afford mono- and C3 symmetric tris(TTF)-triazines as donor-acceptor compounds in which the intramolecular charge transfer (ICT) is modulated by the substitution scheme on TTF and TZ and by chemical or electrochemical oxidation. The TTF-TZ-Cl2 and (SMe)2TTF-TZ-Cl2 derivatives show fully planar structures in the solid state as a consequence of the conjugation between the two units. Electrochemical and photophysical investigations, supported by theoretical calculations, clearly demonstrate that the lowest excited state can be ascribed to the intramolecular charge transfer (ICT) π(TTF)→π*(TZ) transition. The tris(TTF) compound [(SMe)2TTF]3-TZ shows fluorescence when excited in the ICT band, and the emission is quenched upon oxidation. The radical cations TTF(+•) are easily observed in all of the cases through chemical and electrochemical oxidation by steady-state absorption experiments. In the case of [(SMe)2TTF]3-TZ, a low energy band at 5000 cm(-1), corresponding to a coupling between TTF(+•) and TTF units, is observed. A crystalline radical cation salt with the TTF-TZ-Cl2 donor and PF6(-) anion, prepared by electrocrystallization, is described.

A donor-acceptor tetrathiafulvalene ligand complexed to iron(II): synthesis, electrochemistry, and spectroscopy of [Fe(phen)2(TTF-dppz)](PF6)2.

The synthesis and photophysical properties of the complex [Fe(phen)(2)(TTF-dppz)](2+) (TTF-dppz = 4',5'-bis-(propylthio)tetrathiafulvenyl[i]dipyrido[3,2-a:2',3'-c]phenazine, phen = 1,10-phenanthroline) are described. In this complex, excitation into the metal-ligand charge transfer bands results in the population of a high-spin state of iron(II), with a decay lifetime of approximately 1.5 ns, in dichloromethane, at room temperature. An intraligand charge transfer state can also be obtained and has a lifetime of 38 ps. A mechanism for the different states reached is proposed based on transient absorption spectroscopy.

Lanthanide-mediated triangular cationic assemblies: structural and physico-chemical properties.

This contribution investigates Ln(III) complexes formed with a small ditopic ligand, L1, and their structural, thermodynamic and photophysical properties. The spectrophotometric and NMR titrations evidence the triangular assemblies [Ln(3)(L1-H)(3)](6+) at stoichiometric conditions and their properties are discussed in relation to L2-containing analogues. In addition, the dinuclear species, [Ln(2)(L1-H)](5+), is observed with an excess of metal.

Endoscopic vs transfacial resection of sinonasal adenocarcinomas.

OBJECTIVES: Compare the survival and the complication rates of 2 comparable groups of patients who underwent either endoscopic or transfacial resection of a sinonasal adenocarcinoma. STUDY DESIGN: Historical cohort study. SETTING: Tertiary referral center. SUBJECTS AND METHODS: Twenty-four patients with sinonasal adenocarcinomas who recently underwent an endoscopy (the ENDO group, 1999-2009) were compared with 24 patients who underwent a lateral rhinotomy procedure (the LR group, 1993-2007). The present retrospective study included patients who would have had an endoscopic resection in 2011. RESULTS: The groups were comparable in terms of age and sex (P = .49), as well as tumor stages; 43 of the 48 patients had undergone postoperative radiotherapy. There were 13 T1-T2 and 11 T3-T4 tumors in the ENDO group compared with 12 T1-T2 and 12 T3-T4 tumors in the LR group (P = .77). The mean length of follow-up was 38 months for the ENDO group and 89 for the LR group. The overall survival and recurrence-free rates were not significantly different (P = .3 and P = .87, respectively). The median duration of hospitalization was significantly shorter in the ENDO group than in the LR group (4 vs 8 days, P < .0001). The rate of early complications was identical in both groups (12.5%). CONCLUSION: The endoscopic approach is a safe and effective treatment in selected sinonasal adenocarcinoma cases. The early oncological outcome and morbidity associated with the endoscopic approach were comparable with a transfacial approach. Hospitalization was significantly reduced by the endoscopic approach. Although the endoscopic approach is less invasive, it requires an optimal preoperative imaging protocol and an experienced surgical team.

Effect of the addition of a fused donor-acceptor ligand on a Ru(II) complex: synthesis, characterization, and photoinduced electron transfer reactions of [Ru(TTF-dppz)2(Aqphen)]2+.

The synthesis and the photophysical properties of the complex [Ru(TTF-dppz)(2)(Aqphen)](2+) (TTF = tetrathiafulvalene, dppz = dipyrido-[3,2-a:2',3'-c]phenazine, Aqphen = anthraquinone fused to phenanthroline via a pyrazine bridge) are described. In this molecular triad excitation into the metal-ligand charge transfer bands results in the creation of a long-lived charge separated state with TTF acting as electron donor and anthraquinone as terminal acceptor. The lifetime of the charge-separated state is 400 ns in dichloromethane at room temperature. A mechanism for the charge separation involving an intermediate charge-separated state is proposed based on transient absorption spectroscopy.

Virtual screening discovery of new acetylcholinesterase inhibitors issued from CERMN chemical library.

In our quest to find new inhibitors able to inhibit acetylcholinesterase (AChE) and, at the same time, to protect neurons from beta amyloid toxicity, i.e., inhibitors interacting with the catalytic anionic subsite as well as with the peripherical anionic site of AChE, a virtual screening of the Centre d'Etudes et de Recherche sur le Medicament de Normandie (CERMN) chemical library was carried out. Two complementary approaches were applied, i.e., a ligand- and a structure-based screening. Each screening led to the selection of different compounds, but only two were present in both screening results. In vitro tests on AChE showed that one of those compounds presented a very good inhibition activity, of the same order as Donepezil. This result shows the real complementary of both methods for the discovery of new ligands.

Unsymmetrical tripodal ligand for lanthanide complexation: structural, thermodynamic, and photophysical studies.

Two tridentate and one bidentate binding strands have been anchored on a carbon atom to provide a new unsymmetrical tripodal ligand L for Ln(III) coordination. The ligand itself adopts a single conformation in solution stabilized by intramolecular hydrogen bonds evidenced in the solid state. The reaction of L with trivalent lanthanides provides different coordination complexes depending on the metal/ligand ratio. The speciation studies with selected lanthanides were performed in solution by means of NMR, ESMS, and spectrophotometric titrations. Differences in coordination properties along the lanthanide series were evidenced and may be associated with the changes in the ionic size. However, thermodynamic stability constants for the species of the same stoichiometry do not significantly vary. In addition, the structure of the dinuclear complex [Eu(2)L(2)](6+) has been elucidated in the solid state, where the complex crystallizes predominantly as an M-isomer. The crystal structure shows the coordination of two different ligands to each europium cation through tridentate strands, and the europium nine-coordinate sphere is completed with three solvent molecules. Finally, the results of photophysical investigations of [Eu(2)L(2)](6+) are in close agreement with the structural parameters determined by crystallography.

A compactly fused pi-conjugated tetrathiafulvalene-perylenediimide donor-acceptor dyad.

The synthesis and structural characterization of a tetrathiafulvalene-fused perylenediimide molecular dyad is presented. Its largely extended pi-conjugation provides intense optical absorption bands over a wide spectral range. The planar functional molecule exhibits a short-lived nonluminescent excited state attributed to intramolecular charge separation.

Self-assembly of a trinuclear luminescent europium complex.

Triangular luminescent box: Self-assembly of a new multidentate receptor with europium cations results in the formation of trinuclear discrete complexes. X-ray crystallography shows that nine-coordinate cations are linked by ligands to provide a triangular complex in the solid state and in solution. Despite the coordinated solvent molecules, this topologically unusual complex exhibits remarkable luminescent properties.

Imidazole-annulated tetrathiafulvalenes exhibiting pH-tuneable intramolecular charge transfer and redox properties.

In order to study the electronic interactions in donor-acceptor ensembles as a function of pH, an efficient synthetic route to three imidazole-annulated tetrathiafulvalene (TTF) derivatives 1-3 is reported. Their electronic absorption spectra, in view of photoinduced intramolecular charge transfer, and their electrochemical behavior were investigated, and pK(a) values for the two protonation processes on the acceptor unit were determined in organic solvents by photometric titration. The influence of the TTF moiety on these values is discussed.