Folding a Polymer via Two-Point Interaction with an External Folding Agent: Use of H-Bonding and Charge-Transfer Interactions

A polymer containing electron-rich aromatic donors (1,5-dialkoxynaphthalene (DAN)) was coerced into a folded state by an external folding agent that contained an electron-deficient aromatic acceptor (pyromellitic diimide (PM)) unit. The donor-containing polymer was designed to carry a tertiary amine moiety in the linking segment, which served as an H-bonding site for reinforcing the interaction with the acceptor containing folding agent that also bore a carboxylic acid group. The H-bonding interaction of the carboxylic acid and the tertiary amine brings the PDI unit between two adjacent DAN units along the polymer backbone to induce charge-transfer (C-T) interactions, and this in turn causes the polymer chain to form a pleated structure. Evidence for the formation of such a pleated structure was obtained from NMR titration studies and also by monitoring the C-T band in their UV-visible spectra. By varying the length of the segment that links the PDI acceptor to the carboxylic acid group, we showed that the most effective folding agent was the one that had a single carbon spacer, as evident from the highest value of the association constant. Control experiments with propionic acid clearly demonstrated the importance of the additional C-T interactions for venerating the folded structures. Further, solution viscosity measurements in the presence of varying amounts of the folding agent revealed a gradual stiffening of the chain in the case of the PDI carrying carboxylic acid, whereas no such affect was seen in the case of simple propionic acid. These observations were supported by D FT calculations of the interactions of a dimeric model of the polymer with the various folding agents; here too the stability of the complex was seen to be highest in the case of the single carbon spacer.

Design, synthesis and development of novel indolocarbazole derivatives as potential anti-cancer agents

This thesis describes work carried out on the design of new routes to a range of bisindolylmaleimide and indolo[2,3-a]carbazole analogs, and investigation of their potential as successful anti-cancer agents. Following initial investigation of classical routes to indolo[2,3-a]pyrrolo[3,4-c]carbazole aglycons, a new strategy employing base-mediated condensation of thiourea and guanidine with a bisindolyl β-ketoester intermediate afforded novel 5,6-bisindolylpyrimidin-4(3H)-ones in moderate yields. Chemical diversity within this H-bonding scaffold was then studied by substitution with a panel of biologically relevant electrophiles, and by reductive desulfurisation. Optimisation of difficult heterogeneous literature conditions for oxidative desulfurisation of thiouracils was also accomplished, enabling a mild route to a novel 5,6-bisindolyluracil pharmacophore to be developed within this work. The oxidative cyclisation of selected acyclic bisindolyl systems to form a new planar class of indolo[2,3-a]pyrimido[5,4-c]carbazoles was also investigated. Successful conditions for this transformation, as well as the limitations currently prevailing for this approach are discussed. Synthesis of 3,4-bisindolyl-5-aminopyrazole as a potential isostere of bisindolylmaleimide agents was encountered, along with a comprehensive derivatisation study, in order to probe the chemical space for potential protein backbone H-bonding interactions. Synthesis of a related 3,4-arylindolyl-5-aminopyrazole series was also undertaken, based on identification of potent kinase inhibition within a closely related heterocyclic template. Following synthesis of approximately 50 novel compounds with a diversity of H-bonding enzyme-interacting potential within these classes, biological studies confirmed that significant topo II inhibition was present for 9 lead compounds, in previously unseen pyrazolo[1,5-a]pyrimidine, indolo[2,3-c]carbazole and branched S,N-disubstituted thiouracil derivative series. NCI-60 cancer cell line growth inhibition data for 6 representative compounds also revealed interesting selectivity differences between each compound class, while a new pyrimido[5,4-c]carbazole agent strongly inhibited cancer cell division at 10 µM, with appreciable cytotoxic activity observed across several tumour types.

Studies on adhesives for bonding rubber to rubber and rubber to textiles

The primary objective of this investigation has been to develop more efficient and low cost adhesives for bonding various elastomer combinations particularly NR to NR, NR/PB to NR/PB, CR to CR,NR to CR and NR to NBR.A significant achievement of the investigation was the development of solventless and environment friendly solid adhesives for NR to NR and NR/PB to NR/PB particularly for precured retreading. Conventionally used adhesives in this area are mostly NR based adhesive strips in the presence of a dough. The study has shown that an ultra accelerator could be added to the dough just before applying it on the tire which can significantly bring down the retreading time resulting in prolonged tire service and lower energy consumption. Further latex reclaim has been used for the preparation of the solid strip which can reduce the cost considerably.Another significant finding was that by making proper selection of the RF resin, the efficiency and shelflife of the RFL adhesive used for nylon and rayon tire cord dipping can be improved. In the conventionally used RFL adhesive, the resin once prepared has to be added to the latex within 30 minutes and the RFL has to be used after 4 hours maturation time maximum shelf life of the RFL dip solution being 72 hours. In this study a formaldehyde deficient resin was used and hence more flexibility was available for mixing with latex and maturing. It also has a much longer shelf life. In the method suggested in this study, formaldehyde donors were added only in the rubber compound to make up the formaldehyde deficiency in the RFL. The results of this investigation show that the pull through load by employing this method and the conventional method are comparable. This study has also shown that the amount of RF resin with RFL adhesive can be partially replaced by other modifying agents for cost reduction.Cashew nut shell liquid (CNSL) resin can be employed for improving the bonding of dipped nylon and rayon cord with NR.Since CNSL resin cannot be added in the dip solution since it is not soluble in water, it was added in the rubber compound. The amount of wood rosin in the rubber compound can be reduced by using CNSL resin.Another interesting result of the investigation was the use of CR based adhesive modified with chlorinated natural rubber for CR to CR bonding. Addition of chlorinated natural rubber was found to improve sea water resistance of CR based adhesive. In the bonding of a polar rubber like nitrile rubber or polychloroprene rubber to a non polar rubber like natural rubber, an adhesive based on polychloroprene rubber was found to be effective.

Cementation of Prosthetic Restorations: From Conventional Cementation to Dental Bonding Concept

The cementation procedure of metal-free fixed partial dentures exhibits special characteristics about the porcelains and cementation agents, which turns the correct association between these materials necessary. Our purpose in this literature review was to point the main groups of cements associated to metal-free restoration and discuss about the advantages, disadvantages, and recommendations of each one. Our search was confined to the electronic databases PubMed and SciELO and to books about this matter. There are essentially 3 types of hard cement: conventional, resin, or a hybrid of the two. The metal-free restorations can be fixed with conventional or resin cements. The right choice of luting material is of vital importance to the longevity of dental restorative materials. Conventional cements are advantageous when good compressive straight, good film thickness, and water dissolution resistance are necessary. However, they need an ideal preparation, and they are not acid dissolution resistant. Conventional cements are indicated to porcelains that cannot be acid etched. Resin cements represent the choice to metal-free restoration cementation because they present better physical properties and aesthetic than conventional agents.

Biocompatibility of resin-based materials used as pulp-capping agents

Aim To evaluate and compare the response of pulps of rats capped with resin-modified glass-ionomer cement (RMGIC) or self-etching adhesive system.Methodology Class I cavities were prepared on the occlusal surface of 54 maxillary first molars of 27 rats. Pulp exposure was performed on the cavity floor. The following resin-based materials were applied as pulp-capping agents: G1, Clearfil Liner Bond 2V (CLB 2V; Kuraray Co., Japan); G2, Vitrebond (VIT; 3M/ESPE, USA). In group 3 (control group), a calcium hydroxide/saline paste (CH; Labsynth, Brazil) was used. The cavities were restored with amalgam. After 7, 30 and 60 days, the animals were sacrificed and the jaws were processed for microscopic evaluation.Results Despite the inflammatory response caused by the experimental and the control materials at 7 days, pulpal healing associated with calcified barrier formation was observed at 60 days following the pulp therapy. Both resin-based materials promoted a large zone of cell-rich fibrodentine matrix deposition on the pulp horn related to the pulp exposure site, which was larger to VIT than to CLB 2V specimens. Tertiary dentine underneath the fibrodentine matrix was deposited by a layer of elongated pulpal cells. The remaining pulpal tissue exhibited normal histological characteristics. In the control group, healing and dentine-bridge formation was observed at 30 days. Pulpal breakdown occurred only when bacterial infection occurred.Conclusion Both experimental pulp-capping agents allowed pulpal healing characterized by cell-rich fibrodentine and tertiary dentine deposition as well as calcified barrier formation.

Bonding Efficacy of New Self-etching, Self-adhesive Dual-curing Resin Cements to Dental Enamel

Purpose: This study evaluated the efficacy of the union between two new self-etching self-adhesive resin cements and enamel using the microtensile bond strength test.Materials and Methods: Buccal enamel of 80 bovine teeth was submitted to finishing and polishing with metallographic paper to a refinement of #600, in order to obtain a 5-mm(2) flat area. Blocks (2 x 4 x 4 mm) of laboratory composite resin were cemented to enamel according to different protocols: (1) untreated enamel + RelyX Unicem cement (RX group); (2) untreated enamel + Bifix SE cement (BF group); (3) enamel acid etching and application of resin adhesive Single Bond + RelyX Unicem (RXA group); (4) enamel acid etching and application of resin adhesive Solobond M + Bifix SE (BFA group). After 7 days of storage in distillated water at 37 degrees C, the blocks were sectioned for obtaining microbar specimens with an adhesive area of 1 mm(2) (n = 120). Specimens were submitted to the microtensile bond strength test at a crosshead speed of 0.5 mm/min. The results (in MPa) were analyzed statistically by ANOVA and Tu key's test.Results: Enamel pre-treatment with phosphoric acid and resin adhesive (27.9 and 30.3 for RXA and BFA groups) significantly improved (p <= 0.05) the adhesion of both cements to enamel compared to the union achieved with as-polished enamel (9.9 and 6.0 for RX and BF).Conclusion: Enamel pre-treatment with acid etching and the application of resin adhesive significantly improved the bond efficacy of both luting agents compared to the union achieved with as-polished enamel.

Scanning electron microscopy evaluation of the effect of etching agents on human enamel surface

Acid etching promotes microporosities on enamel surface, which provide a better bonding surface to adhesive materials. The purpose of this study was to comparatively analyze the microstructure of enamel surface after etching with 37% phosphoric acid or with two self-etching primers, Non-rinse conditioner (NRC) and Clearfil SE Bond (CSEB) using scanning electron microscopy. Thirty sound premolars were divided into 3 groups with ten teeth each: Group 1: the buccal surface was etched with 37% phosphoric acid for 15 seconds; Group 2: the buccal surface was etched with NRC for 20 seconds; Group 3: the buccal surface was etched with CSEB for 20 seconds. Teeth from Group 1 were rinsed with water; teeth from all groups were air-dried for 15 seconds. After that, all specimens were processed for scanning electron microscopy and analyzed in a Jeol 6100 SEM. The results showed deeper etching when the enamel surface was etched with 37% phosphoric acid, followed by NRC and CSEB. It is concluded that 37% phosphoric acid is still the best agent for a most effective enamel etching.

A comparison of the film thickness of two adhesive luting agents and the effect of thermocycling on their microTBs to feldspathic ceramic.

The aim of the present study was to evaluate the effect of thermocycling (TC) on the microtensile bond strength (microTBS) of two luting agents to feldspathic ceramic and to measure their film thickness (FT). For the microTBS test, sixteen blocks (6.4 x 6.4 x 4.8 mm) were fabricated using a feldspathic ceramic, etched with 10% hydrofluoric acid, rinsed and treated with the silane agent. The ceramic blocks were divided into two groups (n= 8): Gr1: dual-cured resin cement and Gr2: flowable resin. The luting agents were applied on the treated surfaces. Microsticks (1 +/-0. 1mm2) were prepared and stored under two conditions: dry, specimens immediately submitted to the microTBS test, and TC (6,000 cycles; 5 degrees C-55 degrees C). The microTBS was evaluated using a universal testing machine (1 mm/min). The microTBS data (MPa) were submitted to two-way ANOVA and Tukey' test (5%). For the FT test (ISO 4049), 0.05 ml of each luting agent (n=8) was pressed between two Mylar-covered glass plates (150 N) for 180 seconds and light polymerized. FT was measured using a digital paquimeter (Model 727-2001). The data (mm) were submitted to one-way ANOVA. The luting cement did not influence the microTBS results (p= 0.4467). Higher microtensile bond values were found after TC (20.5 +/- 8.6 MPa) compared to the dry condition (13.9 +/- 4. 7MPa), for both luting agents. The luting agents presented similar film thicknesses: Gr1- 0.052 +/- 0.016 mm; Gr2-0.041 +/- 0.003 mm. The luting agents presented similar film thickness and microTBS values, in dry and TC conditions and TC increased the bond strength regardless of the luting agent.

Evaluating the bonding of two adhesive systems to enamel submitted to whitening dentifrices.

The aim of this study was to evaluate by micro-shear bond strength test, the bond strength of composite resin restoration to enamel submitted to whitening dentifrices. Forty bovine teeth were embedded in polystyrene resin and polished. The specimens were randomly divided into eight groups (n=5), according to the dentifrice (carbamide peroxide, hydrogen peroxide and conventional dentifrice) and the adhesive system (Prime & Bond 2.1 and Adper Single Bond 2). Dentifrice was applied for 15 minutes a day, for 21 days. Thirty minutes after the last exposure to dentifrice, the samples were submitted to a bonding procedure with the respective adhesive system. After that, four buttons of resin were bonded in each sample using transparent cylindrical molds. After 24 hours, the teeth were submitted to the micro-shear bond strength test and subsequent analysis of the fracture mode. Data were submitted to analysis of variance and Fisher's PLSD test (alpha = 0.05). The micro-shear bond strength showed no difference between adhesives systems but a significant reduction was found between the control and carbamide groups (p = 0.0145) and the control and hydrogen groups (p = 0.0370). The evaluation of the failures modes showed that adhesive failures were predominant. Cohesive failures were predominant in group IV The use of dentifrice with peroxides can decrease bonding strength in enamel.

Bonding all-ceramic restorations with two resins cement techniques: A clinical report of three-year follow-up

Ceramics have been widely used for esthetic and functional improvements. The resin cement is the material of choice for bonding ceramics to dental substrate and it can also dictate the final esthetic appearance and strength of the restoration. The correct use of the wide spectrum of resin luting agents available depends on the dental tooth substrate. This article presents three-year clinical results of a 41 years old female patient B.H.C complaining about her unattractive smile. Two all-ceramic crowns and two laminates veneers were placed in the maxillary incisors and cemented with a self-adhesive resin luting cement and conventional resin luting cement, respectively. After a three-year follow-up, the restorations and cement/teeth interface were clinically perfect with no chipping, fractures or discoloration. Proper use of different resin luting cements shows clinical appropriate behavior after a three-year follow-up. Self-adhesive resin luting cement may be used for cementing all-ceramic crowns with high predictability of success, mainly if there is a large dentin surface available for bonding and no enamel at the finish line. Otherwise, conventional resin luting agent should be used for achieving an adequate bonding strength to enamel.

Influence of mineralizer agents on the growth of crystalline CeO 2 nanospheres by the microwave-hydrothermal method

Cystalline ceria (CeO2) nanoparticles have been synthesized by a simple and fast microwave-assisted hydrothermal (MAH) under NaOH, KOH, and NH4OH mineralizers added to a cerium ammonium nitrate aqueous solution. The products were characterized by X-ray powder diffraction (XRD), field-emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), Fourier transformed-IR and Raman spectroscopies. Rietveld refinement reveals a cubic structure with a space group Fm3m while infrared data showed few traces of nitrates. Field emission scanning microcopy (FEG-SEM) revealed a homogeneous size distribution of nanometric CeO2 nanoparticles. The MAH process in KOH and NaOH showed most effective to dehydrate the adsorbed water and decrease the hydrogen bonding effect leaving a weakly agglomerated powder of hydrated ceria. TEM micrographs of CeO2 synthesized under MAH conditions reveal particles well-dispersed and homogeneously distributed. The MAH enabled cerium oxide to be synthesized at 100 °C for 8 min. © 2012 Elsevier B.V. All rights reserved.

Surface agents' influence on the flexural strength of bilaminated ceramics

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Design and synthesis of potential antimicrobial agents

Tuberculosis is one of the most devastating diseases in the world primarily due to several decades of neglect and an emergence of multidrug-resitance strains (MDR) of M. tuberculosis together with the increased incidence of disseminated infections produced by other mycobacterium in AIDS patients. This has prompted the search for new antimycobacterial drugs. A series of pyridine-2-, pyridine-3-, pyridine-4-, pyrazine and quinoline-2-carboxamidrazone derivatives and new classes of carboxamidrazone were prepared in an automated fashion and by traditional synthesis. Over nine hundred synthesized compounds were screened for their anti mycobacterial activity against M. fortutium (NGTG 10394) as a surrogate for M. tuberculosis. The new classes of amidrazones were also screened against tuberculosis H37 Rv and antimicrobial activities against various bacteria. Fifteen tested compounds were found to provide 90-100% inhibition of mycobacterium growth of M. tuberculosis H37 Rv in the primary screen at 6.25 μg mL-1. The most active compound in the carboxamidrazone amide series had an MIG value of 0.1-2 μg mL-1 against M. fortutium. The enzyme dihydrofolate reductase (DHFR) has been a drug-design target for decades. Blocking of the enzymatic activity of DHFR is a key element in the treatment of many diseases, including cancer, bacterial and protozoal infection. The x-ray structure of DHFR from M. tuberculosis and human DHFR were found to have differences in substrate binding site. The presence of glycerol molecule in the Xray structure from M. tuberculosis DHFR provided opportunity to design new antifolates. The new antifolates described herein were designed to retain the pharmcophore of pyrimethamine (2,4- diamino-5(4-chlorophenyl)-6-ethylpyrimidine), but encompassing a range of polar groups that might interact with the M. tuberculosis DHFR glycerol binding pockets. Finally, the research described in this thesis contributes to the preparation of molecularly imprinted polymers for the recognition of 2,4-diaminopyrimidine for the binding the target. The formation of hydrogen bonding between the model functional monomer 5-(4-tert-butyl-benzylidene)-pyrimidine-2,4,6-trione and 2,4-diaminopyrimidine in the pre-polymerisation stage was verified by 1H-NMR studies. Having proven that 2,4-diaminopyrimidine interacts strongly with the model 5-(4-tert-butylbenzylidene)- pyrimidine-2,4,6-trione, 2,4-diaminopyrimidine-imprinted polymers were prepared using a novel cyclobarbital derived functional monomer, acrylic acid 4-(2,4,6-trioxo-tetrahydro-pyrimidin-5- ylidenemethyl)phenyl ester, capable of multiple hydrogen bond formation with the 2,4- diaminopyrimidine. The recognition property of the respective polymers toward the template and other test compounds was evaluated by fluorescence. The results demonstrate that the polymers showed dose dependent enhancement of fluorescence emissions. In addition, the results also indicate that synthesized MIPs have higher 2,4-diaminopyrimidine binding ability as compared with corresponding non-imprinting polymers.