Influence of the postpolymerization type and time on the flexural strength and dimensional stability of 3D printed interim resins.

STATEMENT OF PROBLEM: The mechanical strength of 3-dimensionally (3D) printed interim resins is unclear but influenced by printing parameters. Evidence regarding standardization of the postpolymerization type and time for 3D printed interim resins is sparse. PURPOSE: The purpose of this in vitro study was to evaluate the influence of postpolymerization type and time on flexural strength and dimensional stability of 3D printed resins for interim restorations. MATERIAL AND METHODS: A total of 288 bars were 3D printed (Form 2; Formlabs, stereolithography-SLA, 50 µm, 30 degrees), (25×2×2 mm; International Organization for Standardization-ISO 4049:2019) abraded and randomly divided into 9 groups (n=30) according to postpolymerization (Ultraviolet device-UV; Microwave with water-MWA; Microwave without water-MW) and time (15, 20, and 30 minutes for UV; and 5, 8, and 10 minutes for MW and MWA). Each bar was then measured with digital calipers at 11 points for length, thickness, and width before and after postpolymerization to analyze dimensional stability. The flexural strength was then measured (σ; 980.6 N, 1 mm/minute) and the fractured surfaces were analyzed with scanning electron microscopy. The σ (MPa) data were evaluated by using a 2-way analysis of variance (ANOVA) and the Tukey honestly significant difference (HSD) pairwise comparisons test (α=.05). Dimensional stability data (mm) were analyzed by using the Kruskal-Wallis test and Dwass-Steel-Critchlow-Fligner multiple comparisons. The Weibull analysis was performed with σ data. RESULTS: The 2-way ANOVA revealed that all factors and their interaction were significant for σ (P<.001). The UV groups presented the highest σ values, being statistically higher than all MW and MWA groups. The Weibull analysis revealed that postpolymerization UV groups found the highest values regarding the characteristic strength, although the MW 8-minute group (13.71) found the highest value for the Weibull modulus. Furthermore, the Kruskal-Wallis test revealed that only the postpolymerization factor was significant for dimensional stability (P<.001). The postpolymerization microwave groups found greater expansion variations at all times, with the MW 8-minute group (0.78 ±0.54) presenting the greatest variation in dimensional stability. CONCLUSIONS: UV was determined to be the most suitable type of postpolymerization for interim printed resin among the postpolymerization methods, regardless of the application time. The postpolymerization MW groups found greater variations in dimensional stability.

Clinical performance of monolithic polymer-infiltrated ceramic and lithium disilicate posterior crowns: A controlled, randomized, and double-blind clinical trial.

STATEMENT OF PROBLEM: The success rate of monolithic polymer-infiltrated ceramic posterior crowns after 1 year is unclear. PURPOSE: The purpose of this controlled, randomized, and double-blind clinical trial was to evaluate the performance of posterior complete crowns in polymer-infiltrated and lithium disilicate ceramics and to assess the impact of oral rehabilitation on esthetic satisfaction, quality of life, and periodontal health. MATERIAL AND METHODS: A total of 33 crowns were provided in 18 participants allocated to 2 groups: Control (Lithium disilicate-IPS e.max CAD; Ivoclar AG) and Experimental (Polymer-infiltrated ceramic-Vita Enamic; Vita Zahnfabrik). The crowns were evaluated before treatment (T0) and after 1 (T1), 6 (T2), and 12 (T3) months by using modified United States Public Health Service (USPHS) criteria, visual analog scales (VASs), oral impacts on daily performances (OIDP), and periodontal parameters. Survival analysis was performed by using Kaplan-Meier followed by the log-rank test (α=.05). The OIDP and USPHS data were analyzed descriptively while VASs for esthetic satisfaction and periodontal parameters were statistically evaluated by using the Mann-Whitney Friedman, and Wilcoxon post hoc tests. RESULTS: For 18 participants with a mean age of 47.2 years, 19 crowns were manufactured in lithium disilicate and 14 in polymer-infiltrated ceramic. The Kaplan-Meier test revealed similar survival rates of 92.5% for polymer-infiltrated ceramic and 94.7% for lithium disilicate (P>.05). The analysis of periodontal parameters revealed a significant increase in the bleeding on probing (BOP) for polymer-infiltrated ceramics (P=.032) but for lithium disilicate, it was not significant (P=.387). CONCLUSIONS: Survival rates between the evaluated materials were not significantly different, with acceptable clinical performance after 1 year of follow-up.

Developing Amphetamine Certified Reference Materials: From Batch and Continuous-Flow Synthesis to Certification Protocol.

Certified reference materials (CRM) of amphetamine derivatives were produced through a simple, rapid and efficient synthesis in both batch and continuous-flow conditions, accompanied by the development of a comprehensive certification protocol for this class of substances. Our chemistry enabled the synthesis of MDA, MDMA, PMA and PMMA in two steps from safrole and estragole with overall yields of 38-61 % in 48 hours under batch conditions and 61-65 % in 65 minutes under continuous-flow conditions, followed by the development of a certification protocol for these materials through identity checking, homogeneity, stability, and characterization studies. Furthermore, as result of this work, a very pure CRM of MDA.HCl with 99.1±1.4 g/100 g of certified characterization value was produced. Considering the importance of supplying amphetamine calibrants for public security efforts in Forensic Chemistry, the potential therapeutical applications, and responding to the rising demand for the synthesis of CRM, this work presents a pioneering approach for the production of amphetamine and related compounds.

Concise two-step chemical synthesis of molnupiravir.

A concise synthesis of molnupiravir in a one-pot two-step approach starting from uridine is described. Formally, herein, two sets of one-pot two-reaction steps introducing simplicity for purifications and using chemically available reagents are presented. In this context, molnupiravir was obtained in up to 68% overall yield and multigram-scale. In addition, HPLC analysis showed the molnupiravir purity above 99%.

The Effect of a 10-MDP-Based Dentin Adhesive as Alternative for Bonding to Implant Abutment Materials.

Bonding to different dental restorative materials is challenging. This study aimed to evaluate the effect of a 10-MDP-based dentin adhesive on the shear bond strength (SBS) of self-adhesive resin cement (RC) to implant abutment materials. One hundred and twenty specimens were obtained from zirconia (ZO), cobalt-chromium alloy (CoCr), and commercially pure titanium (Ti), which were treated as follows (n = 10): control group-non-treated (CG), 10-MDP-based dentin adhesive (SB), light-cured SB (SB-LC), and zirconia primer (ZP). Blocks of RC were buildup and, after 24 h, were tested for bond strength. Data of SBS (MPa) were submitted to two-way ANOVA and Tukey test (α = 0.05). There was no difference in SBS among materials for CG and ZP, higher SBS were recorded for Ti SB and Ti SB-LC compared to ZO upon the same surface treatments. For the comparisons among treatments, SB-LC showed the highest SBS for CoCr. For ZO and Ti, higher SBS were recorded with SB and SB-LC. No cohesive failures were observed. It was concluded that the surface treatment with 10-MDP-based materials increased the bond strength of the resin cement to abutment materials, which showed to be material dependent.

Lipase-catalyzed acylation of levoglucosan in continuous flow: antibacterial and biosurfactant studies.

Studies involving the transformation of lignocellulosic biomass into high value-added chemical products have been intensively conducted in recent years. Its matrix is mainly composed of cellulose, hemicellulose and lignin, being, therefore, an abundant and renewable source for obtaining several platform molecules, with levoglucosan (LG) standing out. This anhydrous carbohydrate can be acylated to obtain carbohydrate fatty acid esters (CFAEs). Here, these compounds were obtained via enzymatic acylation of LG, commercially obtained (Start BioScience®), with different acyl donors in continuous flow. Through the experimental design using a model reaction, it was possible to optimize the reaction conditions, temperature and residence time, obtaining a maximum conversion at 61 °C and 77 min. In addition, there was a productivity gain of up to 100 times in all comparisons made with the batch system. Finally, CFAEs were applied in tests of interfacial tension and biological activity. For a mixture of 4- and 2-O-lauryl-1,6-anhydroglucopyranose (MONLAU), the minimum interfacial tension (IFTmin) obtained was 96 mN m-1 and the critical micelle concentration (CMC) was 50 mM. Similar values were obtained for a mixture of 4- and 2-O-palmitoyl-1,6-anhydroglucopyranose (MONPAL), not yet reported in the literature, of 88 mN m-1 in 50 mM. For a mixture of 4- and 2-O-estearyl-1,6-anhydroglucopyranose (MONEST) and 4- and 2-O-oleoyl-1,6-anhydroglucopyranose (MONOLE), CMC was higher than 60 mM and IFTmin of 141 mN m-1 and 102 mN m-1, respectively. Promising data were obtained for minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of MONLAU against Staphylococcus aureus strains at 0.25 mM.

Computer Modeling Explains the Structural Reasons for the Difference in Reactivity of Amine Transaminases Regarding Prochiral Methylketones.

Amine transaminases (ATAs) are pyridoxal-5'-phosphate (PLP)-dependent enzymes that catalyze the transfer of an amino group from an amino donor to an aldehyde and/or ketone. In the past decade, the enzymatic reductive amination of prochiral ketones catalyzed by ATAs has attracted the attention of researchers, and more traditional chemical routes were replaced by enzymatic ones in industrial manufacturing. In the present work, the influence of the presence of an α,ß-unsaturated system in a methylketone model substrate was investigated, using a set of five wild-type ATAs, the (R)-selective from Aspergillus terreus (Atr-TA) and Mycobacterium vanbaalenii (Mva-TA), the (S)-selective from Chromobacterium violaceum (Cvi-TA), Ruegeria pomeroyi (Rpo-TA), V. fluvialis (Vfl-TA) and an engineered variant of V. fluvialis (ATA-256 from Codexis). The high conversion rate (80 to 99%) and optical purity (78 to 99% ee) of both (R)- and (S)-ATAs for the substrate 1-phenyl-3-butanone, using isopropylamine (IPA) as an amino donor, were observed. However, the double bond in the α,ß-position of 4-phenylbut-3-en-2-one dramatically reduced wild-type ATA reactivity, leading to conversions of <10% (without affecting the enantioselectivity). In contrast, the commercially engineered V. fluvialis variant, ATA-256, still enabled an 87% conversion, yielding a corresponding amine with >99% ee. Computational docking simulations showed the differences in orientation and intermolecular interactions in the active sites, providing insights to rationalize the observed experimental results.

Cannabidiol Discovery and Synthesis-a Target-Oriented Analysis in Drug Production Processes.

The current state of evidence and recommendations for cannabidiol (CBD) and its health effects change the legal landscape and aim to destigmatize its phytotherapeutic research. Recently, some countries have included CBD as an antiepileptic product for compassionate use in children with refractory epilepsy. The growing demand for CBD has led to the need for high-purity cannabinoids on the emerging market. The discovery and development of approaches toward CBD synthesis have arisen from the successful extraction of Cannabis plants for cannabinoid fermentation in brewer's yeast. To understand different contributions to the design and enhancement of the synthesis of CBD and its key intermediates, a detailed analysis of the history behind cannabinoid compounds and their optimization is provided herein.

GSTP1 rs1695 and rs1871042, and SOD2 rs4880 as molecular markers of lipid peroxidation in blood storage.

BACKGROUND: Red blood cells (RBC) are subject to oxidative stress by reactive oxygen species (ROS) during storage. Molecular characterisation of oxidative stress in stored RBC, which may also occur in other blood components during long periods of storage, is rare. MATERIALS AND METHODS: Our study included 45 healthy RBC donors recruited in Brazil. Blood was collected into standard Grifols® Triple Bags containing CPD SAG-M. Haematological values, biochemical data, and oxidative stress markers were assessed weekly during storage until 42 days after collection. GSTM1 and GSTT1 were determined by multiplex-polymerase chain reaction (PCR), while GSTP1 rs1695 and rs1871042, CAT rs1001179, and SOD2 rs4880 were evaluated by real-time PCR. RESULTS: A direct proportional relationship was found between storage time and levels of ROS and thiobarbituric acid reactive substances (TBARS, indicators of lipid peroxidation) (p<0.001). These parameters were indirectly proportional to ABTS values (p<0.001). The plasma concentration of TBARS was associated with GSTP1 303AG/GG, GSTP1 -16CT/TT, and SOD2 47CT/TT genotypes. Single-nucleotide polymorphisms at the CAT C-262T gene were not associated with TBARS, nor were oxidative markers of ROS. DISCUSSION: Prolonged storage may result in the onset of erythrocyte deterioration. Our results clearly indicate that erythrocytes are capable of attenuating ROS for 2 weeks of storage. We observed an association between elevated TBARS levels and the presence of GSTP1 and SOD2 variants in stored RBC. Although notable for heterozygous variants, this association was even stronger for the homozygous variants GSTP1 rs1695 (303GG), GSTP1 rs1871042 (-16TT), and SOD2 rs4880 (47TT). These findings accentuate the importance of genetic factors in storage lesions and will expand our understanding and consideration of endogenous and exogenous causes in improving clinical treatment with blood transfusions.

Lipases of Endophytic Fungi Stemphylium lycopersici and Sordaria sp.: Application in the synthesis of solketal derived Monoacylglycerols.

Monoacylglycerols (MAGs) are amphiphilic compounds with wide range of applications such as emulsifiers, solubility agents, and chiral building blocks. These compounds are currently produced by chemical approaches involving alkaline glycerolysis or esterification under high temperatures and pressure, resulting in low yields and with by-products. Lipase-catalyzed processes have been alternative tools to provide more ecological approaches since MAGs can be obtained under milder reaction conditions and with higher selectivity. However, just a few papers have been explored the potential of endophytic fungi as lipase sources. In this work we summarized the screening of lipolytic activity of endophytic fungus S. lycopersici and Sordaria spp isolated from vegetal species collected in Jurubatiba Sandbank National Park, RJ, Brazil, as well as its applications as biocatalysts on the lipase-catalyzed synthesis of solketal 1-MAG derivatives. As a result, the crude enzymatic extract of S. lycopersici showed 98 U/mL and 110 U/mL of hydrolytic activity after 72 h and 96 h, respectively, against 74 U/mL (96 h) and, 86 U/mL (120 h) expressed by enzymatic extract of Sordaria spp.. Concerning the esterification activity, both crude enzymatic extracts and lyophilized fungi showed about 80 % conversion into ethyl oleate, in 100 min. On solketal derived 1-MAG synthesis, S. lycopersici both lyophilized and immobilized in polyurethane (PU) forms showed more than 75 % of conversion in the presence and absence of organic solvents. On MAG recycle assays, the PU biocatalyst could be reused after five reaction cycles while for the ethyl oleate synthesis, PU biocatalyst could be reused after six reaction cycles. Both microorganisms, immobilized in polyurethane, were successfully applied as biocatalysts in esterification reactions for solketal 1-MAG derivative production, in a solvent-free media.

Enzyme Immobilization in Covalent Organic Frameworks: Strategies and Applications in Biocatalysis.

The development of efficient catalytic systems is a fundamental aspect for the straightforward production of chemicals. During the last years, covalent organic frameworks (COFs) emerged as an exciting class of organic nanoporous materials. Due to their pre-designable structure, they can be prepared with distinct physicochemical characteristics, specific pore sizes, and tunable functional groups. Moreover, associated with their stability in different media, these materials are considered promising supports for enzyme immobilization. Herein, it is highlighted the recent literature of enzyme immobilization in COFs, the main immobilization strategies, and the catalytic applications of these composites.

Continuous-flow synthesis of dimethyl fumarate: a powerful small molecule for the treatment of psoriasis and multiple sclerosis.

Dimethyl fumarate (DMF) is a methyl ester of fumaric acid and has recently gained attention due to its use as a pro-drug in different pharmaceutical preparations, besides the low price of the final molecule and no active patents being available for the synthesis of DMF, the prices of multiple sclerosis treatment are still high. In our continuous effort for the development of process intensification strategies towards the synthesis of active pharmaceutical ingredients, here we present our work on a cascade methodology for dimethyl fumarate synthesis in short reaction times and quantitative yields.

Enzyme-Decorated Covalent Organic Frameworks as Nanoporous Platforms for Heterogeneous Biocatalysis.

Sustainability in chemistry heavily relies on heterogeneous catalysis. Enzymes, the main catalyst for biochemical reactions in nature, are an elegant choice to catalyze reactions due to their high activity and selectivity, although they usually suffer from lack of robustness. To overcome this drawback, enzyme-decorated nanoporous heterogeneous catalysts were developed. Three different approaches for Candida antarctica lipase B (CAL-B) immobilization on a covalent organic framework (PPF-2) were employed: physical adsorption on the surface, covalent attachment of the enzyme in functional groups on the surface and covalent attachment into a linker added post-synthesis. The influence of the immobilization strategy on the enzyme uptake, specific activity, thermal stability, and the possibility of its use through multiple cycles was explored. High specific activities were observed for PPF-2-supported CAL-B in the esterification of oleic acid with ethanol, ranging from 58 to 283 U mg-1 , which was 2.6 to 12.7 times greater than the observed for the commercial Novozyme 435.

Short communication: Influence of retainer configuration and loading direction on the stress distribution of lithium disilicate resin-bonded fixed dental prostheses: 3D finite element analysis.

The present study elucidates the mechanical performance of different designs of resin-bonded fixed dental prostheses made of lithium disilicate simulating masticatory loads of anterior or canine guidance. A three-dimensional model of maxilla was constructed containing central incisor and canine teeth, with edentulous space of the lateral incisor. Three designs of prosthesis were created: retained in central incisor (1-I), retained in canine (1-C) and fixed in both teeth (2-IC). The computational analysis was performed for load in canine and central incisor separately (100N, 45°). The tensile and shear stresses were calculated for the resin-bonded fixed dental prosthesis, bonding surface of each retainer and cement layer using 3D finite element analysis. The 20 highest stress values were analyzed using two-way ANOVA and post-hoc Tukey test, all with α = 5%. The computational analysis showed that 2-retainer resin-bonded fixed dental prosthesis presented the worst prognosis regardless of the mandibular movement. ANOVA showed that Mandibular movement*Retainer interaction influenced on the tensile and shear stresses values (p < 0.01). Higher stresses were observed in the connector region for all groups (13-82.2 MPa; 11-70.2 MPa). In order to reduce the stress concentration in the resin-bonded fixed dental prosthesis and the retainer made of lithium disilicate, the occlusion may serve as the selection criteria of the unitary abutment for better sustainability.

Morphochemical characterization, microhardness, water sorption, and solubility of regular viscosity bulk fill and traditional composite resins.

OBJECTIVE: To evaluate the morphology of filler particles, chemical composition, microhardness (MH), water sorption (WSp), and solubility (WSl) of a regular viscosity bulk fill and traditional composite resins. METHODS: Eighty samples (Ø:5 mm; height: 4 mm) were prepared according to the factors "composite" (Aura/SDI, FiltekZ250 XT/3M, Aura Bulk Fill/SDI, and Filtek Bulk Fill/3M) and "filling technique" (incremental and bulk) (n = 10). Vickers MH was measured on the top and bottom surfaces of each samples, and then WSp and WSl were obtained by means of mass gain and loss. Morphology of filler particles and chemical characteristics of composites were evaluated by scanning electron microscopy (SEM) and energy dispersity spectroscopy (EDS) in additional samples (n = 1/group). Data were analyzed using two- and three-way ANOVA and Tukey's tests (p < .05). RESULTS: No significant difference was found for WSp among the groups. Comparing composites in the incremental technique, Aura bulk fill composite showed lower WSI than the other materials and in the bulk fill technique, Filtek Bulk Fill showed the lowest value. Filtek Bulk Fill showed higher MH than the other composites on the bottom surface when samples were produced by bulk filling. CONCLUSION: The composites presented good physical properties, but the bulk fill ones showed better results for the bottom microhardness and solubility, although chemical elements and morphology were similar in general.

The effect of air-particle abrasion and a zirconia primer application on resin cement bonding strength to zirconia.

BACKGROUND: This study aimed to evaluate the influence of surface treatments on the bond strength between a zirconia-based ceramic and two resin cements. METHODS: Eighty blocks (5.25×3.74×4.5 mm) of a zirconia-based ceramic were divided into eight groups (N.=10) according to the factors "surface treatment" (air-particle abrasion with Al2O3 or Al2O3/SiO2 and zirconia primer) and "cement" (conventional resin cement and self-adhesive resin cement). After the surface treatments, cylinders of each resin cement (Ø=3.5 mm, height: 3 mm) were built up on the zirconia surface and photo-activated (40 s). The samples were stored in water for 30 days at 37 °C, followed by shear bond strength test in a universal testing machine (1 mm/min). Data were analyzed by ANOVA and Tukey test (α=0.05). RESULTS: Regarding the surface treatments, all strategies were statistically different from each other. The Cojet achieved the higher bond strength values, followed by Signum Zirconia Bond. The resin cements were also statistically different from each other, since the U200 achieved higher bond strength values. The interaction between the factors was also significant. Most of the failures were adhesive and mixed. CONCLUSIONS: Regardless of the cement used, the air-particle abrasion with alumina coated by silica particles improved bond strength.

Continuous-flow protocol for the synthesis of enantiomerically pure intermediates of anti epilepsy and anti tuberculosis active pharmaceutical ingredients.

Continuous-flow production of chiral intermediates plays an important role in the development of building blocks for Active Pharmaceutical Ingredients (APIs), being α-amino acids and their derivatives widely applied as building blocks. In this work we developed two different strategies for the synthesis of intermediates used on the synthesis of levetiracetam/brivaracetam and ethambutol. The results obtained show that methionine methyl ester can be continuously converted to the desired ethambutol intermediate by RANEY® Nickel dessulfurization/reduction strategy whereas levetiracetam/brivaracetam intermediates could be synthesized by both RANEY® Nickel (without H2) and Pd/C-H2 approach or by photochemical desulfurization.

Y-TZP surface behavior under two different milling systems and three different accelerated aging protocols.

BACKGROUND: To evaluate the influence of aging and milling system on zirconia surface roughness (SR) and phase transformation. METHODS: Eighty crowns were divided in two groups according to yttria-stabilized tetragonal zirconia polycrystalline (Y-TZP) ceramic milling system (CAD-Neodent or MAD-Zirkonzahn). The crowns were submitted to different aging protocols (N.=10): 1) no aging; 2) autoclaving; 3) pH cycling; or 4) thermocycling. Next, the samples were submitted to an optical profilometry analysis to determine differences in the SR (µm). An X-ray diffraction analysis (XRD) was performed to quantify the percentage of monoclinic phase transformation. SR data was analyzed by two-way ANOVA (α=0.5%). RESULTS: Aging protocol (P=0.42) and milling system (P=0.08) had no influence on the SR. However, the number of monoclinic phases was influenced by the autoclaving and pH cycling. CONCLUSIONS: The surface roughness of zirconia-based crowns was not influenced by low temperature degradation or milling system. Regarding the phase transformation, autoclaving and pH-cycling aging presented a monoclinic phase increase when compared to the control group and thermocycled groups.

Combination of the Suzuki-Miyaura Cross-Coupling Reaction with Engineered Transaminases.

The combination of enzymatic and chemical reaction steps is one important area of research in organic synthesis, preferentially as cascade reactions in one-pot to improve total conversion and achieve high operational stability. Here, the combination of the Suzuki-Miyaura reaction is described to synthesize biaryl compounds followed by a transamination reaction. Careful optimization of the reaction conditions required for the chemo- and biocatalysis reaction enabled an efficient two-step-one-pot reaction yielding the final chiral amines with excellent optical purity (>99 % ee) in up to 84 % total conversion. Key to the success was the protein engineering of the amine transaminases from Asperguillus fumigatus (4CHI-TA) where single alanine mutations increased the conversion up to 2.3-fold. Finally, the transfer to a continuous flow system after immobilization of the best 4CHI-TA variant is demonstrated.

Impact of continuous flow chemistry in the synthesis of natural products and active pharmaceutical ingredients.

We present a comprehensive review of the advent and impact of continuous flow chemistry with regard to the synthesis of natural products and drugs, important pharmaceutical products and definitely responsible for a revolution in modern healthcare. We detail the beginnings of modern drugs and the large scale batch mode of production, both chemical and microbiological. The introduction of modern continuous flow chemistry is then presented, both as a technological tool for enabling organic chemistry, and as a fundamental research endeavor. This part details the syntheses of bioactive natural products and commercial drugs.