I. Synthetic Studies Toward the Total Synthesis of Polycyclic Natural Products – Communesin F, Perophoramidine and Ineleganolide. II. Nickel Catalyzed Intramolecular C–O Bond Formation

Expedient synthetic approaches to the highly functionalized polycyclic alkaloids communesin F and perophoramidine are described using a unified approach featuring a key decarboxylative allylic alkylation to access a crucial and highly congested 3,3-disubstituted oxindole. Described are two distinct, stereoselective alkylations that produce structures in divergent diastereomeric series possessing the critical vicinal all-carbon quaternary centers needed for each synthesis. Synthetic studies toward these challenging core structures have revealed a number of unanticipated modes of reactivity inherent to these complex alkaloid scaffolds. Finally, a previously unknown mild and efficient deprotection protocol for the o-nitrobenzyl group is disclosed – this serendipitous discovery permitted a concise endgame for the formal syntheses of both communesin F and perophoramidine.

In addition, the atroposelective synthesis of PINAP ligands has been accomplished via a palladium-catalyzed C–P coupling process through dynamic kinetic resolution. These catalytic conditions allow access to a wide variety of alkoxy- and benzyloxy-substituted PINAP ligands in high enantiomeric excess.

An efficient and exceptionally mild intramolecular nickel-catalyzed carbon–oxygen bond-forming reaction between vinyl halides and primary, secondary, and tertiary alcohols has been achieved. This operationally simple method allows direct access to cyclic vinyl ethers in high yields in a single step.

Finally, synthetic studies toward polycyclic ineleganolide are described. The entire fragmented carbon framework has been constructed from this work. Highly (Z)-selective olefination was achieved by the method by the Ando group.

Synthesis and Characterization of Double Metal Hexacyanoferrates

Manganese Hexacyanoferrate (MnHCF) and nickel doped manganese hexacyanoferrate were synthesized by simple co-precipitation method. The water content and chemical formula was obtained by TGA and MP-AES measurements, functional groups by FT-IR analysis, the crystal structure by PXRD and a local geometry by XAS. Elemental species of cycled samples were further investigated by TXM and 2D XRF. Electrochemical tests were performed in the glass cell. With addition of nickel, vacancies and water content increased in the sample. Crystal structure changed from monoclinic to cubic. Ni disturbed the local structure of Mn, site, however, almost no change was observed in Fe site. After charge/discharge cycling of MnHCF intercalation was already found in the peripheries of charged species after 20 cycle in 2D XRF analysis and randomly distributed intercalated regions after 50 cycles in TXM analysis. Cyclic voltammetry showed that peak-to-peak separation is increasing in case of the addition of Ni to MnHCF.

Microtensile Bond Strength Of Methacrylate And Silorane Resins To Enamel And Dentin.

The aim of this study was to evaluate the microtensile bond strength (µTBS) of two substrates (enamel and dentin) considering two study factors: type of composite resin [methacrylate-based (Filtek Supreme) or silorane-based (Filtek LS)] and aging time (24 h or 3 months). Twenty human molars were selected and divided into 2 groups (n=10) considering two dental substrates, enamel or dentin. The enamel and dentin of each tooth was divided into two halves separated by a glass plate. Each tooth was restored using both tested composite resins following the manufacturer's instructions. The samples were sectioned, producing 4 sticks for each composite resin. Half of them were tested after 24 h and half after 3 months. µTBS testing was carried out at 0.05 mm/s. Data were analyzed by three-way ANOVA and Tukey's HSD tests at α=0.05. Significant differences between composite resins and substrates were found (p<0.05), but no statistically significant difference was found for aging time and interactions among study factors. The methacrylate-based resin showed higher µTBS than the silorane-based resin. The µTBS for enamel was significantly higher than for dentin, irrespective of the composite resin and storage time. Three months of storage was not sufficient time to cause degradation of the bonding interaction of either of the composite resins to enamel and dentin.

Effect Of Composite Containing An Iodonium Salt On The Bond Strength Of Brackets To Bovine Enamel.

This study investigated the effect of the incorporation of an iodonium salt in experimental composites, on the bond strength of metallic brackets bonded to bovine teeth. Two hundred and seventy bovine teeth were embedded in self-curing acrylic resin and divided into 18 groups (n=15), according to the experimental composite with an iodonium salt at molar concentrations 0 (control), 0.5, or 1%; the light-activation times (8, 20 and 40 s); and the storage times (10 min or 24 h). Metallic brackets were fixed on the tooth surface using experimental composites. Photoactivation was performed with a quartz-tungsten-halogen light-curing unit curing unit for 8, 20 and 40 s. The specimens were stored in distilled water at 37 °C for 10 min or 24 h and submitted to bond strength test at 0.5 mm/min. The data were subjected to three-way ANOVA and Tukey's test (α=0.05). The Adhesive Remnant Index (ARI) was used to classify the failure modes. The shear bond strengths (MPa) at 10 min for light-activation times of 8, 20 and 40 s were: G1 - 4.6, 6.9 and 7.1; G2 - 8.1, 9.2 and 9.9; G3 - 9.1, 10.4 and 10.7; and at 24 h were: G1 - 10.9, 11.1 and 11.7; G2 - 11.8, 12.7 and 14.2; G3 - 12.1, 14.4 and 15.8. There was a predominance of ARI score 3 for groups with 10 min storage time, and ARI score 2 for groups with 24 h storage time. In conclusion, the addition of iodonium salt (C05 and C1) to the experimental composite may increase the bond strength of brackets to bovine enamel using reduced light exposure times.

Dentin Bond Strength Of A Fluoride-releasing Adhesive System Submitted To Ph-cycling.

To evaluate the microtensile bond strength (µTBS) of a fluoride-containing adhesive system submitted to a pH-cycling and storage time regimen for primary outcomes. As secondary outcomes the fluoride released amount was evaluated. Twelve dentin surfaces from sound third molar were divided into 2 groups according to adhesive systems: Clearfil SE Protect (PB) and Clearfil SE Bond (SE). Sticks obtained (1.0 mm2) from teeth were randomly divided into 3 subgroups according to storage regimen model: immediate (24h); 5-month deionized water (W); and pH-cycling model (C). All sticks were tested for µTBS in a universal testing machine. Fluoride concentration was obtained from 1-4 days and 30-day in W and 1-4 days in demineralization (DE)/remineralization (RE) solutions from C, using a fluoride-specific electrode. µTBS and fluoride released data were, respectively, submitted to ANOVA in a split plot design and Tukey, and Friedman' tests (a=0.05). There was no significant interaction between adhesive system and storage regimen for µTBS. W showed the lowest µTBS values. There was no significant difference between 24 h and C models for µTBS. There was no significant difference between adhesive systems. Failure mode was predominantly cohesive within composite for the 24 h and W, for the C group it was mixed for SE and cohesive within composite for PB adhesive system. Fluoride concentrations in the DE/RE solutions were less than 0.03125 ppm and not detected in W. In conclusion, the fluoride-containing adhesive system performed similarly to the regular one. Hydrolytic degradation is the main problem with both adhesive systems, regardless of fluoride contents.

Dentine Bond Strength And Antimicrobial Activity Evaluation Of Adhesive Systems.

This study evaluated the dentine bond strength (BS) and the antibacterial activity (AA) of six adhesives against strict anaerobic and facultative bacteria. Three adhesives containing antibacterial components (Gluma 2Bond (glutaraldehyde)/G2B, Clearfil SE Protect (MDPB)/CSP and Peak Universal Bond (PUB)/chlorhexidine) and the same adhesive versions without antibacterial agents (Gluma Comfort Bond/GCB, Clearfil SE Bond/CSB and Peak LC Bond/PLB) were tested. The AA of adhesives and control groups was evaluated by direct contact method against four strict anaerobic and four facultative bacteria. After incubation, according to the appropriate periods of time for each microorganism, the time to kill microorganisms was measured. For BS, the adhesives were applied according to manufacturers' recommendations and teeth restored with composite. Teeth (n=10) were sectioned to obtain bonded beams specimens, which were tested after artificial saliva storage for one week and one year. BS data were analyzed using two-way ANOVA and Tukey test. Saliva storage for one year reduces the BS only for GCB. In general G2B and GCB required at least 24h for killing microorganisms. PUB and PLB killed only strict anaerobic microorganisms after 24h. For CSP the average time to eliminate the Streptococcus mutans and strict anaerobic oral pathogens was 30min. CSB showed no AA against facultative bacteria, but had AA against some strict anaerobic microorganisms. Storage time had no effect on the BS for most of the adhesives. The time required to kill bacteria depended on the type of adhesive and never was less than 10min. Most of the adhesives showed stable bond strength after one year and the Clearfil SE Protect may be a good alternative in restorative procedures performed on dentine, considering its adequate bond strength and better antibacterial activity.

Two-dimensional Ultrasound And Ultrasound Elastography Imaging Of Trigger Points In Women With Myofascial Pain Syndrome Treated By Acupuncture And Electroacupuncture: A Double-blinded Randomized Controlled Pilot Study.

Chronic pain has been often associated with myofascial pain syndrome (MPS), which is determined by myofascial trigger points (MTrP). New features have been tested for MTrP diagnosis. The aim of this study was to evaluate two-dimensional ultrasonography (2D US) and ultrasound elastography (UE) images and elastograms of upper trapezius MTrP during electroacupuncture (EA) and acupuncture (AC) treatment. 24 women participated, aged between 20 and 40 years (M ± SD = 27.33 ± 5.05) with a body mass index ranging from 18.03 to 27.59 kg/m2 (22.59 ± 3.11), a regular menstrual cycle, at least one active MTrP at both right (RTPz) and left trapezius (LTPz) and local or referred pain for up to six months. Subjects were randomized into EA and AC treatment groups and the control sham AC (SHAM) group. Intensity of pain was assessed by visual analogue scale; MTrP mean area and strain ratio (SR) by 2D US and UE. A significant decrease of intensity in general, RTPz, and LTPz pain was observed in the EA group (p = 0.027; p < 0.001; p = 0.005, respectively) and in general pain in the AC group (p < 0.001). Decreased MTrP area in RTPz and LTPz were observed in AC (p < 0.001) and EA groups (RTPz, p = 0.003; LTPz, p = 0.005). Post-treatment SR in RTPz and LTPz was lower than pre-treatment in both treatment groups. 2D US and UE effectively characterized MTrP and surrounding tissue, pointing to the possibility of objective confirmation of subjective EA and AC treatment effects.

Pain Intensity And Cervical Range Of Motion In Women With Myofascial Pain Treated With Acupuncture And Electroacupuncture: A Double-blinded, Randomized Clinical Trial.

Acupuncture stimulates points on the body, influencing the perception of myofascial pain or altering physiologic functions. The aim was to evaluate the effect of electroacupuncture (EAC) and acupuncture (AC) for myofascial pain of the upper trapezius and cervical range of motion, using SHAM acupuncture as control. Sixty women presenting at least one trigger point at the upper trapezius and local or referred pain for more than six months were randomized into EAC, AC, and SHAM groups. Eight sessions were scheduled and a follow-up was conducted after 28 days. The Visual Analog Scale assessed the intensity of local and general pain. A fleximeter assessed cervical movements. Data were analyzed using paired t or Wilcoxon's tests, ANOVA or Friedman or Kruskal-Wallis tests and Pearson's correlation (α=0.05). There was reduction in general pain in the EAC and AC groups after eight sessions (P<0.001). A significant decrease in pain intensity occurred for the right trapezius in all groups and for the left trapezius in the EAC and AC groups. Intergroup comparisons showed improvement in general pain in the EAC and AC groups and in local pain intensity in the EAC group (P<0.05), which showed an increase in left rotation (P=0.049). The AC group showed increases in inclination (P=0.005) sustained until follow-up and rotation to the right (P=0.032). EAC and AC were effective in reducing the pain intensity compared with SHAM. EAC was better than AC for local pain relief. These treatments can assist in increasing cervical range of motion, albeit subtly.

In vitro evaluation of an alternative method to bond molar tubes

Despite the advances in bonding materials, many clinicians today still prefer to place bands on molar teeth. Molar bonding procedures need improvement to be widely accepted clinically. OBJECTIVE: The purpose of this study was to evaluate the shear bond strength when an additional adhesive layer was applied on the occlusal tooth/tube interface to provide reinforcement to molar tubes. MATERIAL AND METHODS: Sixty third molars were selected and allocated to the 3 groups: group 1 received a conventional direct bond followed by the application of an additional layer of adhesive on the occlusal tooth/tube interface, group 2 received a conventional direct bond, and group 3 received a conventional direct bond and an additional cure time of 10 s. The specimens were debonded in a universal testing machine. The results were analyzed statistically by ANOVA and Tukey's test (α=0.05). RESULTS: Group 1 had a significantly higher (p<0.05) shear bond strength compared to groups 2 and 3. No difference was detected between groups 2 and 3 (p>0.05). CONCLUSIONS: The present in vitro findings indicate that the application of an additional layer of adhesive on the tooth/tube interface increased the shear bond strength of the bonded molar tubes.

Effect of cyclic load on vertical misfit of prefabricated and cast implant single abutment

OBJECTIVES: The purpose of this in vitro study was to evaluate misfit alterations at the implant/abutment interface of external and internal connection implant systems when subjected to cyclic loading. MATERIAL AND METHODS: Standard metal crowns were fabricated for 5 groups (n=10) of implant/abutment assemblies: Group 1, external hexagon implant and UCLA cast-on premachined abutment; Group 2, internal hexagon implant and premachined abutment; Group 3, internal octagon implant and prefabricated abutment; Group 4, external hexagon implant and UCLA cast-on premachined abutment; and Group 5, external hexagon implant and Ceraone abutment. For groups 1, 2, 3 and 5, the crowns were cemented on the abutments and in group 4 crowns were screwed directly on the implant. The specimens were subjected to 500,000 cycles at 19.1 Hz of frequency and non-axial load of 133 N in a MTS 810 machine. The vertical misfit (μm) at the implant/abutment interface was evaluated before (B) and after (A) application of the cyclic loading. Data were analyzed statistically by using two-away ANOVA and Tukey's post-hoc test (p<0.05). RESULTS: Before loading values showed no difference among groups 2 (4.33±3.13), 3 (4.79±3.43) and 5 (3.86±4.60); between groups 1 (12.88±6.43) and 4 (9.67±3.08), and among groups 2, 3 and 4. However, groups 1 and 4 were significantly different from groups 2, 3 and 5. After loading values of groups 1 (17.28±8.77) and 4 (17.78±10.99) were significantly different from those of groups 2 (4.83±4.50), 3 (8.07±4.31) and 5 (3.81±4.84). There was a significant increase in misfit values of groups 1, 3 and 4 after cyclic loading, but not for groups 2 and 5. CONCLUSIONS: The cyclic loading and type of implant/abutment connection may develop a role on the vertical misfit at the implant/abutment interface.

Effect of cement type and water storage time on the push-out bond strength of a glass fiber post

This study investigated the effects of the cement type and the water storage time on the push-out bond strength of a glass fiber post. Glass fiber posts (Fibrekor, Jeneric Pentron) were luted to post spaces using a self-cured resin cement (C&B Cement [CB]), a glass ionomer cement (Ketac Cem [KC]) or a resin-modified glass ionomer cement (GC FujiCEM [FC]) according to the manufacturers’ instructions. For each luting agent, the specimens were exposed to one of the following water storage times (n=5): 1 day (T1), 7 days (T7), 90 days (T90) and 180 days (T180). Push-out tests were performed after the storage times. Control specimens were not exposed to water storage, but subjected to the push-out test 10 min after post cementation. Data (in MPa) were analyzed by Kruskal-Wallis and Dunn`s test (α=0.05). Cement type and water storage time had a significant effect (p<0.05) on the push-out bond strength. CB showed significantly higher values of retention (p<0.05) than KC and FC, irrespective of the water storage time. Water storage increased significantly the push-out bond strength in T7 and T90, regardless of the cement type (p<0.05). The results showed that fiber posts luted to post spaces with the self-cured resin cement exhibited the best bonding performance throughout the 180-day water storage period. All cements exhibited a tendency to increase the bond strength after 7 and 90 days of water storage, decreasing thereafter.

Influence of different adhesive systems on the pull-out bond strength of glass fiber posts

This in vitro study evaluated the tensile bond strength of glass fiber posts (Reforpost - Angelus-Brazil) cemented to root dentin with a resin cement (RelyX ARC - 3M/ESPE) associated with two different adhesive systems (Adper Single Bond - 3M/ESPE and Adper Scotchbond Multi Purpose (MP) Plus - 3M/ESPE), using the pull-out test. Twenty single-rooted human teeth with standardized root canals were randomly assigned to 2 groups (n=10): G1- etching with 37% phosphoric acid gel (3M/ESPE) + Adper Single Bond + #1 post (Reforpost - Angelus) + four #1 accessory posts (Reforpin - Angelus) + resin cement; G2- etching with 37% phosphoric acid gel + Adper Scotchbond MP Plus + #1 post + four #1 accessory posts + resin cement. The specimens were stored in distilled water at 37°C for 7 days and submitted to the pull-out test in a universal testing machine (EMIC) at a crosshead speed of 0.5 mm/min. The mean values of bond strength (kgf) and standard deviation were: G1- 29.163 ± 7.123; G2- 37.752 ±13.054. Statistical analysis (Student's t-test; a=0.05 showed no statistically significant difference (p<0.05) between the groups. Adhesive bonding failures between resin cement and root canal dentin surface were observed in both groups, with non-polymerized resin cement in the apical portion of the post space when Single Bond was used (G1). The type of adhesive system employed on the fiber post cementation did not influence the pull-out bond strength.

Effect of deproteinization and tubular occlusion on microtensile bond strength and marginal microleakage of resin composite restorations

Dentin adhesion procedure presents limitations, especially regarding to lifetime stability of formed hybrid layer. Alternative procedures have been studied in order to improve adhesion to dentin. OBJECTIVE: The aim of this study was to evaluate in vitro the influence of deproteinization or dentin tubular occlusion, as well as the combination of both techniques, on microtensile bond strength (µTBS) and marginal microleakage of composite resin restorations. MATERIAL AND METHODS: Extracted erupted human third molars were randomly divided into 4 groups. Dentin surfaces were treated with one of the following procedures: (A) 35% phosphoric acid gel (PA) + adhesive system (AS); (B) PA + 10% NaOCl + AS; (C) PA + oxalate + AS and (D) PA + oxalate + 10% NaOCl + AS. Bond strength data were analyzed statistically by two-way ANOVA and Tukey's test. The microleakage scores were analyzed using Kruskal-Wallis and Mann-Whitney non-parametric tests. Significance level was set at 0.05 for all analyses. RESULTS: µTBS data presented statistically lower values for groups D and B, ranking data as A>C>B>D. The use of oxalic acid resulted in microleakage reduction along the tooth/restoration interface, being significant when used alone. On the other hand, the use of 10% NaOCl alone or in combination with oxalic acid, resulted in increased microleakage. CONCLUSIONS: Dentin deproteinization with 10% NaOCl or in combination with oxalate significantly compromised both the adhesive bond strength and the microleakage at interface. Tubular occlusion prior to adhesive system application seems to be a useful technique to reduce marginal microleakage.

Short-Term effect of COX-2 selective inhibitor as an adjunct for the treatment of periodontal disease: a clinical double-blind study in humans

Adjunctive therapeutic strategies that modulate the inflammatory mediators can play a significant role in periodontal therapy. In this double-blind, placebo-controlled study, 60 subjects diagnosed as periodontitis patients were evaluated for 28 days after periodontal treatment combined with selective cyclooxygenase-2 (COX-2) inhibitor. The experimental group received scaling and root planning (SRP) combined with the Loxoprofen antiinflammatory drug (SRP+Loxoprofen). The control group received SRP combined with placebo (SRP+placebo). Plaque index (PI), probing pocket depth (PD) and bleeding on probing (BOP) were monitored with an electronic probe at baseline and after 14 and 28 days. Both groups displayed clinical improvement in PD, PI and BOP. They also showed statistically similar values (p>0.05) of PD reduction on day 14 (0.4 mm) and on day 28 (0.6 mm). At the baseline, few deeper sites (>7 mm) from SRP+Loxoprofen group were responsible and most PD reduction was observed after 14 days (p<0.05). The percentage of remaining deep pockets (>7 mm) after 14 days in the SRP+Loxoprofen group was significantly lower (p<0.05) than in the SRP+placebo group. Loxoprofen presents potential effect as an adjunct of periodontal disease treatment, but long-term clinical trials are necessary to confirm its efficacy.

Bonding agent underneath sealant: shear bond strength to oil-contaminated

This study evaluated in vitro the shear bond strength of a resin-based pit-and-fissure sealant (Fluroshield - F) associated with either an ethanol-based (Adper Single Bond 2 - SB) or an acetone-based (Prime & Bond - PB) adhesive system under conditions of oil contamination. Mesial and distal enamel surfaces from 30 sound third molars were randomly assigned to 2 groups (n=30): I - no oil contamination; II - oil contamination. Contamination (0.25 mL during 10 s) was performed after 37% phosphoric acid etching with an air/oil spray. The specimens were randomly assigned to subgroups, according to the bonding protocol adopted: subgroup A - F was applied to enamel without an intermediate bonding agent layer; In subgroups B and C, SB and PB, respectively, were applied, light-cured, and then F was applied and light-cured. Shear bond strength was tested at a crosshead speed of 0.5 mm/min in a universal testing machine. Means (± SD) in MPa were: IA-11.28 (±1.84); IIA-12.02 (±1.15); IB-9.73 (±2.38); IIB-9.62 (±2.29); IC-28.30 (±1.63); and IIC-25.50 (±1.91). It may be concluded that the oil contamination affected negatively the sealant bonding to enamel and the acetone-based adhesive system (PB) layer applied underneath the sealant was able to prevent its deleterious effects to adhesion.