Development of chiral nitrogen ligands for application in homogeneous catalysis

2008/2009Aim of this thesis is the synthesis of enantiomerically pure ligands for their application in asymmetric catalysis. In particular, the work is focused on the synthesis of three different classes of ligands. Chapters 2 and 3 deal with the synthesis of CNN-pincer and N-Nˈ(bipyridine) ligands respectively, obtained in both enantiomeric forms by stereocomplementary chemoenzymatic methods, while Chapter 4 presents the synthesis of P-N type ligands obtained from L-proline. The activity of the complexes that containing the optically pure synthesized ligands was also investigated.XXII Ciclo198

Synthesis of chiral, enantiopure allylic amines by the Julia olefination of \u3b1-amino esters

The four-step conversion of a series of N-Boc-protected l-amino acid methyl esters into enantiopure N-Boc allylamines by a modified Julia olefination is described. Key steps include the reaction of a lithiated phenylalkylsulfone with amino esters, giving chiral \u3b2-ketosulfones, and the reductive elimination of related \u3b1-acetoxysulfones. The overall transformation takes place under mild conditions, with good yields, and without loss of stereochemical integrity, being in this respect superior to the conventional Julia reaction of \u3b1-amino aldehydes

Photobiomodulation at Multiple Wavelengths Differentially Modulates Oxidative Stress In Vitro and In Vivo

Photobiomodulation (PBM) is emerging as an effective strategy for the management of multiple inflammatory conditions, including oral mucositis (OM) in cancer patients who receive chemotherapy or radiotherapy. Still, the poor understanding of the mechanisms by which the light interacts with biological tissues and the heterogeneity of light sources and protocols employed worldwide significantly limits its applicability. Reactive oxygen species (ROS) are massively generated during the early phases of OM and play a major role in the pathogenesis of inflammation in general. Here, we report the results of a clinical and experimental study, aimed at evaluating the effect of laser light at different wavelengths on oxidative stress in vivo in oncologic patients suffering from OM and in vitro in two cell types abundantly present within the inflamed oral mucosa, neutrophil polymorphonuclear (PMN) granulocytes, and keratinocytes. In addition to standard ROS detection methods, we exploited a roGFP2-Orp1 genetically encoded sensor, allowing specific, quantitative, and dynamic imaging of redox events in living cells in response to oxidative stress and PBM. We found that the various wavelengths differentially modulate ROS production. In particular, the 660\u2009nm laser light increases ROS production when applied either before or after an oxidative stimulus. In contrast, the 970\u2009nm laser light exerted a moderate antioxidant activity both in the saliva of OM patients and in both cell types. The most marked reduction in the levels of ROS was detected in cells exposed either to the 800\u2009nm laser light or to the combination of the three wavelengths. Overall, our study demonstrates that PBM exerts different effects on the redox state of both PMNs and keratinocytes depending on the used wavelength and prompts the validation of a multiwavelength protocol in the clinical settings

Efficient Synthesis of New Fluorinated Building Blocks by means of Hydroformylation

Hydroformylation of fluorinated alkenes is an efficient method for the preparation of fluorinated functionalized building blocks for the synthesis of biologically active target structures. In this article we summarize known hydroformylation reactions of fluorinated olefins and we add new results from our research groups. Particular attention is paid to the remarkable influence of organofluorine substituents on catalyst activity, regio- and stereoselectivity of the hydroformylation reaction

From Erosion to Remineralization: The Possible Role of Two Topic Home Devices Used as Combined Treatment

Severe dental erosion could be one of the complications of gastroesophageal reflux disease and food disorders such as bulimia nervosa. The aim of the present in vitro study was to evaluate the remineralization efficiency and the erosion prevention capability obtained by combining the use of Elmex Erosion Protection (Elm-EP) and GC Tooth Mousse (GC-TM) in cases of strongly eroded enamel surfaces. Twenty-four specimens of bovine tooth were superficially treated with hydrochloric acid to mimic severe erosion conditions. The specimens were divided into 3 groups accordingly to a different remineralizing treatment for 15 days: immersion in artificial remineralizing saliva, brushing with Elm-EP and brushing with Elm-EP in association with a daily application of GC-TM paste. After the remineralization procedures, the specimens were exposed to a treatment with acid. The effectiveness of the treatments were assessed by surface profilometric analysis and scanning electron microscopy at four different steps. Furthermore, the quantity of the Ca2+ lost during erosion was determined. The combined action of Elm-EP and GC-TM led to a 50% roughness decrease of critically eroded dental surfaces. The tandem use of Elmex Erosion Protection and GC Tooth Mousse resulted a promising protecting strategy for the prevention of the dental mineral loss

Development of di-methacrylate quaternary ammonium monomers with antibacterial activity

Nine antibacterial di-methacrylate monomers based on bis-quaternary ammonium salts (bis-QAMs) were synthesized and structurally characterized. The biological activity of the bis-QAMs was tested in terms of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) on different bacterial strains achieving promising results and, in most cases, a complete bactericidal effect using a bis-QAM concentration lower than 1 mg/mL. Two of the structures showed comparable and superior activity against S. mutans than the commercial monomer 12-methacryloyloxydodecyl pyridinium bromide (MDBP). All the bis-QAMs here described were able to inhibit S. mutans biofilm formation at a concentration equal to the MIC value. From the analysis of the obtained data, some correlation regarding the structure and the antibacterial activity of the bis-QAMs could be drawn: a flexible alkyl C12 spacer between the two quaternary ammonium moieties increased the monomer antibacterial effect in comparison to the aromatic ones; the equilibrium between hydrophobic and hydrophilic moieties was directly correlated to the bactericidal range of action; the increase of the steric hindrance of the ammonium side groups might be both advantageous or disadvantageous to the antibacterial efficacy depending on the whole monomer chemical structure. Even though the possible correlation between the monomer structures and their bacteriostatic or bactericidal effect is under investigation, the monomers exhibited low cytotoxicity on human dental pulp stem cells, confirming their promising potential in the dental materials' field

Influence of Thickness and Shade on the Color of Layered Novel Nanohybrid Composite Systems

The influence of the layer thickness and composite shade on the final color of Ceram.X composites (Dentsply Sirona) was tested, selecting five intermediate-translucency Ceram.X Universal shades, three high-translucency Ceram.X Duo "enamel" shades, and four low-translucency Ceram.X Duo "dentin" shades. Using cylindrical molds, 850 specimens were obtained, representing the whole array of possible Universal single specimens (in seven thicknesses, ranging from 1.0 to 4.0 mm in 0.5-mm increments) and Duo combinations. The CIELAB coordinates of each specimen were determined with a spectrophotometer. Different thicknesses and composites were compared with Clark's \u394E. The difference in color among specimens of different thicknesses was material-dependent. The thickness and shade of the composite markedly affected the color yield of the Ceram.X system. For each shade of the Universal systems, only one Duo enamel-dentin combination corresponded

Evaluation of the degree of conversion and rate of cure of a new BIS-GMA-free nanohybrid composite

Aim: The polymerization efficiency of the newintroduced Bis-GMA-free nanohybrid composite containing pre-polymerized spherical filler Ceram. X\uaeDuo-D3 (CXDD3, Dentsply) was investigated in terms of degree of conversion (DC) and rate of cure (RC). The obtained results were compared with those of two commonly used composites of equivalent dentin shade: the nanohybrid Tetric EvoCeram\uae-A3.5 (TECA3.5, Ivoclar Vivadent) and the nanofilled FiltekTMSupreme XTE-D3 (FSAD3, 3M ESPE). Methods: DC was evaluated using a Fourier Transform Infra-Red Attenuated Total Reflectance equipment (FTIR-ATR, Nicolet 6700-ThermoFisher) recording the photopolymerization kinetic (1 spectrum/s). Each composite (N=10) was placed on the FTIRATR diamond stage in a 2-mm thick silicon mold and photopolymerized for 40s with the LED curing-light SmartLite Focus\uae(Dentsply). Infrared (IR) spectra were obtained between 4000cm 121 and 500cm 121 at a resolution of 16cm 121. DC was calculated as: DC = [1 - (R40)/(R0)] * 100. Where R0 represents the ratio between the intensity of the reactive group signal (C=C, 1635cm-1) and the internal reference (C=O, 715cm-1) of the unpolymerized material and R40 the same ratio after 40s of photopolymerization. The kinetic trend was obtained plotting DC vs. time for all the materials. The kinetic curves were fitted with a second-grade polynomial expression, from the first derivative of the fitting, the RC at selected times (5, 10s) was calculated. RC 640.5 between two consecutive times was considered as arbitrary value for the curve plateau.All data were subjected to statistical analysis with dedicated software (Statistical Package for Social Sciences Software v.15.0, SPSS Inc.) and tested for the assumptions for the use of parametrical tests: the normality of the distribution and the equality of variances were verified with a Shapiro-Wilk test and a Levene test, respectively. The influence of the materials\u2019 composition on the DC and RC values was evaluated by one-way multivariate analysis of variance (ANOVA), pairwise comparison between groups were performed with a Scheff\ue9 post hoc test at a preset \u3b1=0.05. Separately, RC values registered for each material after 5 and 10s of curing time were compared with a paired-samples t-test. Results: For all tested materials, the obtained DC after 40s of photopolymerization was lower than 50%. Among the tested composites, CXDD3 showed the highest DC (p 0.05). Within each composite, RC at 10s resulted significantly lower than that at 5s (pTECA3.5>FSAD3. CXDD3 showed the faster kinetic reaching the plateau (RC 640.5) after 25s. Differently, FSA3D and TECA3.5 showed a significantly slower kinetic (p<0.05): TECA3.5 kinetic trend reached the plateau after 30s of photopolymerization while the RC of FSA3D slightly decreased with time with a pseudo-linear trend never reaching the RC value set as plateau. Conclusions: Within the limitation of the present in vitro study, it is possible to assess that DC and RC of the studied composites were materialdependent: CXDD3, characterized by a Bis-GMA-free composition, achieved higher DC thanks to a faster kinetic. However, considering that for all the tested composites the average DC remained below 50% after 40s of photopolymerization, an increase of the curing-time or a reduction of the layer thickness may be suggested in the clinical setting of the dentine shaded composites

New Chiral P-N Ligands for the Regio- and Stereoselective Pd-Catalyzed Dimerization of Styrene

Two new chiral, enantiomerically pure, hybrid P-N ligands, namely (2R,5S)-2-phenyl-3-(2-pyridyl)-1,3-diaza-2-phosphanicyclo[3,3,0]octan-4-one (1) and (2R,5S)-2-phenyl-3-(2-pyridyl)-1,3-diaza-2-phosphanicyclo[3,3,0]octane (2), have been synthesized starting from L-proline. The two ligands differ in the presence or not of a carbonyl group in the diazaphosphane ring. Their coordination chemistry towards Pd(II) was studied by reacting them with [Pd(CH3)Cl(cod)]. A different behaviour was observed: ligand 2 shows the expected bidentate chelating behaviour leading to the mononuclear Pd-complex, while ligand 1 acts as a terdentate ligand giving a dinuclear species. The corresponding cationic derivatives were obtained from the palladium neutral complexes, both as mono- and dinuclear derivatives, and tested as precatalysts for styrene dimerization, yielding E-1,3-diphenyl-1-butene regio- and stereoselectively as the sole product. A detailed analysis of the catalytic behaviour is reported

In vitro study on conditioned dental root surfaces: evaluation of wettability, smear layer, and blood clot adhesion

Objectives: The aim \ufeffwas to investigate the efficacy of citric acid and ethylenediaminetetraacetic acid (EDTA)\ufeff-based treatments on smear layer removal and blood clot formation and stabilization. Method and materials: After scaling and root planing, 126 root samples were divided into seven groups treated with: deionized water; saline; citric acid solution; Ultradent Citric Acid gel; EDTA solution; EDTA-based PrefGel; or untreated. Each group was divided into three subgroups: I for the evaluation of smear layer removal and surface wettability, II and III for the evaluation of blood clot formation and stabilization in static or dynamic rinsing conditions. Results: Conditioning agent treatments increased surface wettability with respect to untreated samples (Ultradent: 45\ufeff\u202f\ub1\u202f1 degrees, P\u202f=\u202f6.2\u202f 7\u202f10-3; EDTA: 36\ufeff\u202f\ub1\u202f5\ufeff degrees, P\u202f=\u202f8.9\u202f 7\u202f10-7; PrefGel: 47\ufeff\u202f\ub1\u202f7\ufeff degrees, P\u202f=\u202f3.2\u202f 7\u202f10-2). Smear layer removal (30% to 60% with respect to untreated samples) was observed for all the conditioning agents. Clot was absent on untreated samples and samples treated with deionized water. Clot quality was significantly higher for samples treated with conditioning agents (P\u202f\u202f.05). A statistically significant difference (P\u202f=\u202f.027) was observed for clot coverage of \ufeffthe saline group, comparing static and dynamic rinsing, confirming the positive effect of treatments on clot stabilization. Conclusions: The use of conditioning agents improves smear layer removal and clot formation and stabilization with respect to scaling and root planing procedure only, which is, however, considered an essential procedure to promote wound healing in periodontal surgery