ARTICLE | doi:10.20944/preprints202012.0594.v1
Subject: Chemistry And Materials Science, Biomaterials Keywords: benzoxazines; polybenzoxazines; diaminodiphenylmethane; 3,3’-dichloro-4,4’-diaminodiphenylmethane; heterocycles; thermosetting binders
Online: 23 December 2020 (15:30:55 CET)
As a result of this work, a previously unreported benzoxazine monomer based on 3,3'-dichloro-4,4'-diaminodiphenylmethane was obtained, characterized by 1H and 13C NMR spectroscopy, and its thermal and rheological properties were studied. A comparison between the properties of benzoxazines based on diamines (3,3'-dichloro-4,4'-diaminodiphenylmethane and 4,4’-diaminodimethylmethane). The effect of the reaction medium on the structure of the oligomeric fraction and the overall yield of the main product was studied. The synthesized monomers can be used as thermo- and fire-resistant binders for polymer composite materials, as well as hardeners for epoxy resins.
ARTICLE | doi:10.20944/preprints202306.0387.v1
Subject: Chemistry And Materials Science, Analytical Chemistry Keywords: kinetics performances; BSA-gold nanozymes; 3,3’,5,5’-thetramethylbenzidine; 3,3’-diaminobenzidine
Online: 6 June 2023 (05:41:48 CEST)
It is well-known that the peroxidase enzyme catalyzes the oxidation of different substrates such as 3,3’,5,5’-thetramethylbenzidine, and 3,3’-diaminobenzidine, however, the affinity of different substrates to the enzyme and consequently and catalytic performances of the enzyme toward different substrates is not same, resulting in different kinetics indexes. As the BSA-gold nanozymes are considered artificial peroxidase enzymes, hence, the kinetics indexes of these nanozymes should also be varied by varying their substrate. Hence, in this work, a comparative study was performed on the kinetics performances of BSA-gold nanozymes for enzyme-mediated oxidations of 3,3’,5,5’-thetramethylbenzidine, and 3,3’-diaminobenzidine. The results showed that the Km value of BSA-gold nanozymes was 0.03 mM and 0.72 mM toward TMB and DAB, in order, to reveal the higher affinity (lower Km) of TMB for binding to nanozyme active nodes compared to its alternative substrate, DAB. In contrast, the Vmax was found to be 263 nM sec-1 and 185 nM sec-1 for nanozmye-mediated oxidation of TMB and DAB, respectively. The higher Vmax of the nanozyme-mediated oxidation of TMB revealed that the catalytic efficiency of BSA-Au nanozymes toward TMB oxidation is higher (about 1.5-fold) than that of the DAB oxidation. The difference between the kinetic indexes of TMB and DAB may be related to their different oxidation pathways and their different reactivity. In fact, the DAB oxidizes via an n-electron irreversible oxidation pathway to produce an indamine polymer. While TMB nanozyme-mediated oxidation has occurred upon a 2-electron reversible mechanism for the production of a cation radical. These different pathways resulted in different kinetic performances.
ARTICLE | doi:10.20944/preprints202009.0536.v1
Subject: Chemistry And Materials Science, Physical Chemistry Keywords: 3,3’,5,5’-tetramethylbenzidine; reactive oxygen species (ROS); reactive nitrogen species (RNS); photoacoustic probes; optical sensors; singlet oxygen
Online: 23 September 2020 (04:17:34 CEST)
Photoacoustic imaging is attracting a great deal of interest owing to its distinct advantages over other imaging techniques such as fluorescence or magnetic resonance image. Availability of photoacoustic probes for reactive oxygen and nitrogen species (ROS/RNS) could shed light on a plethora of biological processes mediated by these key intermediates. Tetramethylbenzidine (TMB) is a non-toxic and non-mutagenic colorless dye that develops a distinctive blue color upon oxidation. In this work we have investigated the potential of TMB as photoacoustic probe for ROS/RNS. Our results indicate that TMB reacts with hypochlorite, hydrogen peroxide, singlet oxygen and nitrogen dioxide to produce the blue oxidation product, while ROS such as the superoxide radical anion, sodium peroxide, hydroxyl radical or peroxynitrite yield a colorless oxidation product. TMB does not penetrate Escherichia coli cytoplasm but is capable of detecting singlet oxygen generated in its outer membrane.
ARTICLE | doi:10.20944/preprints202310.1592.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: α-synuclein aggregates; 4,4'-diarylbisthiazole; binding affinity; Hantzsch thiazole synthesis; lipophilicity; O-fluoroethylation; O-fluoroPEGylation; O-methylation
Online: 25 October 2023 (08:36:57 CEST)
The α-synucleinopathies are a group of neurodegenerative diseases characterized by the deposition of α-synuclein aggregates (α-syn) in the brain. Currently, there is no suitable tracer to enable a definitive early diagnosis of these diseases. We reported candidates based on 4,4'-disarylbisthiazole (DABTA) scaffold with a high affinity towards α-syn and excellent selectivity over Aβ and tau fibrils. Based on prior in silico studies a focused library of 23 halide-containing and O-methylated DABTAs was prepared. The DABTAs were synthesized via a modified two-step Hantzsch thiazole synthesis, characterized, and used in competitive binding assays against [3H]PiB, and [3H]DCVJ. The DABTAs gave an overall chemical yield of 15 – 71%, with a calculated lipophilicity of 2.5 – 5.7. The ligands demonstrated an excellent affinity to α-syn with both [3H]PiB and [3H]DCVJ: Ki 0.1 – 4.9 nM and up to 20 – 3900-fold selectivity over Aβ and tau fibrils. It could be concluded that in-silico simulation is useful for the rational design of a new generation of DABTAs. Further investigation of the leads in the next step is encouraged: radiolabeling of the ligands with radioisotopes such as fluorine-18 or carbon-11 for in vivo, ex vivo and translational research and for further in vitro experiments on human-derived protein aggregates.
COMMUNICATION | doi:10.20944/preprints202203.0377.v1
Subject: Chemistry And Materials Science, Organic Chemistry Keywords: p-nitrophenyl hydrazone; solvent-free; green synthesis; p-nitrophenyl hydrazine; mechanochemistry; dichloro p-nitrophenyl hydrazone; methoxy p-nitrophenyl hydrazone; solvent-based; spectroscopy; elucidation.; p-Nitrophenyl hydrazone; solvent-free; green synthesis; p-Nitrophenyl hydrazine; mechanochemistry; dichloro and methoxy p-Nitrophenyl hydrazone; solvent-based; structure elucidation; spectroscopy
Online: 29 March 2022 (08:53:22 CEST)
We conducted a comparative study on the development of two synthetic methods. The solvent-free synthesis is a green chemistry method developed in a bid to ameliorate environmental adverse effects of the conventional solvent-based synthesis. The synthesis of novel dichloro and polymethoxy p-nitrophenylhydrazones through solvent free technique gave moderate to high yields which were however lower than those of the solvent-based method. The established solvent-free approach has several benefits, including universality and simplicity of the approach, catalyst-free conditions, non-use of an organic solvent, quick reaction time, fast and efficient workup, and un-solvated pure products in moderate to high yields.
ARTICLE | doi:10.20944/preprints202010.0339.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: aging; paternal exposure; sperm; semen; epigenetics; sncRNA; piRNA; miRNA; 2,2′,4,4′-tetrabromodiphenyl ether; PBDE; BDE-47; perinatal; environment.
Online: 16 October 2020 (08:10:16 CEST)
Advanced paternal age at fertilization is a risk factor for multiple disorders in offspring and may be linked with age-related epigenetic changes in fathers sperm. Understanding of aging-related epigenetic changes in sperm and environmental factors that modify such changes is needed. Here we characterize changes in sperm sncRNA between young pubertal and mature rats. We also analyze modification of these changes by exposure to environmental xenobiotic 2,2’,4,4’-tetrabromodiphenyl ether (BDE-47). SncRNA libraries prepared from epididymal spermatozoa were sequenced and analyzed using DESeq 2. Distribution of small RNA fractions changed with age, with fractions mapping to rRNA and lncRNA decreasing and fractions mapping to tRNA and miRNA increasing. 249 miRNA, 908 piRNA and 227 tRNA-derived RNA were differentially expressed (2-fold change, FDR p ≤ 0.05) between age groups in control animals. Differentially expressed miRNA and piRNA were enriched for protein-coding targets involved in development and metabolism, piRNA were enriched for LTR targets. BDE-47 accelerated age dependent changes in sncRNA in younger animals, decelerated these changes in older animals and increased the variance in expression of all sncRNA. Our results indicate that the natural aging process has profound effects on sperm sncRNA profiles and this effect may be modified by environmental exposures.
ARTICLE | doi:10.20944/preprints202308.2171.v1
Subject: Chemistry And Materials Science, Biomaterials Keywords: 1-(2-((3-amino-2-hydroxypropyl)amino)ethyl)-1'-ethyl-[4,4'-bipyridine]-1,1'-diium; Iron Polymer-Complex; MTT; A375 cells.
Online: 31 August 2023 (10:43:55 CEST)
In the present study, linear novel polymer poly(1-(2-((3-amino-2-hydroxypropyl)amino)ethyl)-1'-ethyl-[4,4'-bipyridine]-1,1'-di-ium) (poly(AHAEBD)) and its complex with iron (ΙΙΙ) ([Fe(poly(AHAEBD)2].Na3) were synthesized and then their anticancer effects on A375 human malignant melanoma cells line were evaluated. The structure of the synthesized compounds was confirmed using Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance spectroscopy (1HNMR), field emission scanning electron microscopy (FE-SEM), X-ray energy diffraction analysis (EDS) and gel permeation chromatography (GPC). Also, the cytotoxicity of cisplatin as a reference, on A375 melanoma cell line was tested. The IC50 of polymer-complex [Fe(poly(AHAEBD)2].Na3 (0.71 µg/mL), cisplatin (4.58 µg/mL) and poly(AHAEBD) (1.73 µg/mL) were obtained. Our results revealed that the polymer-complex [Fe(poly(AHAEBD)2].Na3 exhibited better performance compared to cisplatin. Furthermore, the coordination with iron (III) enhanced the cytotoxicity levels of poly(AHAEBD). According to these findings, the synthesized polymer-complex demonstrates remarkable potential as an anti-cancer agent. This study could provide the basis for future research focused on employing this new polymer-complex for in vivo testing, highlighting its potential for therapeutic applications.
ARTICLE | doi:10.20944/preprints202010.0641.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: aging; paternal exposure; sperm; advanced paternal age; epigenetics; DNA methylation; RRBS, 2,2′,4,4′-tetrabromodiphenyl ether; PBDE; BDE-47; perinatal; environment
Online: 30 October 2020 (13:37:14 CET)
Advanced paternal age at fertilization has been suggested to be a risk factor for neurodevelopmental, psychiatric and other disorders in offspring. One emerging hypothesis suggests that altered offspring phenotype is linked with age-related accumulation of epigenetic changes in the sperm of fathers. Given that paternal age is increasing in the developed world, understanding aging-related epigenetic changes in sperm is needed as well as environmental factors that modify such changes. In this study, we characterize age-dependent changes in sperm DNA methylation profiles between young pubertal (postnatal day (PNDs) 65) and mature (PND120) Wistar rats. We also analyze these changes in rats exposed perinatally to 0.2 mg/kg of ubiquitous environmental xenobiotic 2,2’,4,4’-tetrabromodiphenyl ether (BDE-47). Reduced representation bisulfite sequencing (RRBS) libraries were prepared from caudal epididymal sperm DNA and differentially methylated regions (DMRs; ≥ 10x coverage depth, ≥ 3 CpGs per cluster, ≥ 5% methylation change, q < 0.05) were identified via MethPipe package. In control animals, 5,319 age-dependent DMRs were identified, with 99.3% DMRs hypermethylated in mature animals compared to young pubertal rats. These age-related DMRs were enriched for functional categories essential for embryonic development, such as pattern specification, forebrain and sensory organ development, Hippo and Wnt pathways. Age-related changes in sncRNA, reported in different study, target similar list of genes and biological categories.In BDE-47 exposed rats, sperm DNA methylation was higher in young pubertal and lower in mature animals when compared to controls, which resulted in a significant attenuation in the number of age-dependent DMRs (N = 189) identified in the exposed group. In conclusion, our results indicate that the natural aging process has profound effects on sperm methylation levels and this effect may be modified by environmental exposures. Moreover, our results further support the role of epigenetic mechanisms as a likely link betwen paternal age and offspring health and development.
ARTICLE | doi:10.20944/preprints201810.0599.v1
Subject: Chemistry And Materials Science, Organic Chemistry Keywords: (R)-1-(4-Amino-3,5-dichlorophenyl)-2-bromoethan-1-ol; (S)-N-(2,6-dichloro-4-(1-hydroxyethyl)phenyl)acetamide; clenbuterol; ketoreductase; chiral chromatography
Online: 25 October 2018 (08:44:19 CEST)
(R)-1-(4-Amino-3,5-dichlorophenyl)-2-bromoethan-1-ol has been synthesised in 93% enantiomeric excess (ee) by asymmetric reduction of the corresponding ketone catalysed by a ketoreductase and NADPH as the co-factor in DMSO. (S)-N-(2,6-Dichloro-4-(1-hydroxyethyl)phenyl)acetamide has been synthesised in >98% ee by the same system. Both synthons are potential precursors for clenbuterol enantiomers. Clenbuterol is a β2-agonist used in veterinary treatment of asthma in several countries. The drug is listed on the World Anti-doping Agency’s Prohibited list due to its effect on increased protein synthesis in the body. However, racemic clenbuterol has recently been shown to reduce the risk of Parkinson’s disease. In order to reveal which one (or both) of the enantiomers that cause this effect, the pure enantiomers need to be studied separately. Our biocatalytic approach in order to obtain enantiopure clenbuterol should be applicable to industrial scale.
ARTICLE | doi:10.20944/preprints202310.0271.v1
Subject: Chemistry And Materials Science, Organic Chemistry Keywords: 4-Aryl-4,9H-3-methyl-1-phenyl-1H-pyrazolo[3,4-b]quinoline, multicomponent reactions, L-proline, 4,4-(phenylmethylene)-bis-(3-methyl-1-phenylpyrazol-5-oles).
Online: 5 October 2023 (10:27:18 CEST)
Looking for effective synthetic methods for 1H-pyrazolo[3,4-b]quinolines preparation, we came across a procedure where in a three component reaction catalyzed by L-proline, 4-aryl-4,9-dihydro-1H-pyrazolo[3,4-b]quinolines are formed. These compounds can be easily oxidized to a fully aromatic system, which gave hope for a synthetic method that could replace e.g. Friedländer condensation, often used for this purpose, although severely limited by the availability of suitable substrates. However, after careful repetition of the procedures described in the publication, it turned out that the compounds described therein do not form at all. The actual compounds turned out to be 4,4-(phenylmethylene)-bis-(3-methyl-1-phenylpyrazol-5-oles). 4-Aryl-4,9-dihydro-1H-pyrazolo[3,4-b]quinolines were prepared by another method and used as standards to compare the products formed in the original procedure.