Evaluation of the Biocompatibility of CS-Graphene Oxide Compounds In Vivo.

In the last few years, graphene oxide (GO) has gained considerable importance in scaffold preparation for tissue engineering due to the presence of functional groups that allow the interaction between the extracellular matrix and the components of the cellular membrane. The interaction between GO and chitosan (CS) can not only improve the biomechanical properties of the scaffold but also generate a synergistic effect, facilitating tissue recovery. In vivo studies on GO are scarce; therefore, biocompatibility tests on CS-GO scaffolds and bone regeneration experiments on critical size defects were carried out on Wistar rats. Scaffolds made of CS, CS-GO 0.5%, and CS-GO 1% were prepared and implanted on Wistar rats cranial bones for three months. Scaffold samples were analyzed through histochemistry and scanning electron microscopy. The analysis performed showed reabsorption of the material by phagocytic activity and new bone formation. The CS-GO 0.5% formulation gave the best performance in bone regeneration, with excellent biocompatibility. These results show the potential of this compound for tissue regeneration opening and medical applications.

Equilibrium and Kinetic Study of Lead and Copper Ion Adsorption on Chitosan-Grafted-Polyacrylic Acid Synthesized by Surface Initiated Atomic Transfer Polymerization.

In this work, we synthesized chitosan grafted-polyacrylic acid (CS-g-PA) through surface-initiated atom transfer radical polymerization (SI-ATRP). We also studied the adsorption process of copper and lead ions onto the CS-g-PA surface. Adsorption equilibrium studies indicated that pH 4.0 was the best pH for the adsorption process and the maximum adsorption capacity over CS-g-PA for Pb2+ ions was 98 mg·g-1 and for Cu2+ it was 164 mg·g-1, while for chitosan alone (CS), the Pb2+ adsorption capacity was only 14.8 mg·g-1 and for Cu2+ it was 140 mg·g-1. Furthermore, the adsorption studies indicated that Langmuir model describes all the experimental data and besides, pseudo-second-order model was suitable to describe kinetic results for the adsorption process, demonstrating a larger kinetic constant of the process was larger for Pb2+ than Cu2+. Compared to other adsorbents reported, CS-g-PA had comparable or even superior adsorbent capacity and besides, all these results suggest that the new CS-g-PA polymers had potential as an adsorbent for hazardous and toxic metal ions produced by different industries.

Synthesis and Application of Scaffolds of Chitosan-Graphene Oxide by the Freeze-Drying Method for Tissue Regeneration.

Several biomaterials, including natural polymers, are used to increase cellular interactions as an effective way to treat bone injuries. Chitosan (CS) is one of the most studied biocompatible natural polymers. Graphene oxide (GO) is a carbon-based nanomaterial capable of imparting desired properties to the scaffolds. In the present study, CS and GO were used for scaffold preparation. CS was extracted from the mycelium of the fungus Aspergillus niger. On the other hand, GO was synthesized using an improved Hummers-Offemann method and was characterized by Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, atomic force microscopy (AFM), X-ray diffraction (XRD), and dynamic light scattering (DLS). Subsequently, three formulations (GO 0%, 0.5%, and 1%) were used to prepare the scaffolds by the freeze-drying technique. The scaffolds were characterized by FTIR, thermogravimetric analysis (TGA), and scanning electron microscopy (SEM), to determine their thermal stability and pore size, demonstrating that their stability increased with the increase of GO amount. Finally, the scaffolds were implanted, recollected 30 days later, and studied with an optical microscope, which evidenced the recovery of the tissue architecture and excellent biocompatibility. Hence, these results strongly suggested the inherent nature of chitosan/graphene oxide (CS/GO) scaffolds for their application in bone tissue regeneration.

An automated pipeline integrating AlphaFold 2 and MODELLER for protein structure prediction.

The ability to predict a protein's three-dimensional conformation represents a crucial starting point for investigating evolutionary connections with other members of the corresponding protein family, examining interactions with other proteins, and potentially utilizing this knowledge for the purpose of rational drug design. In this work, we evaluated the feasibility of improving AlphaFold2's three-dimensional protein predictions by developing a novel pipeline (AlphaMod) that incorporates AlphaFold2 with MODELLER, a template-based modeling program. Additionally, our tool can drive a comprehensive quality assessment of the tertiary protein structure by incorporating and comparing a set of different quality assessment tools. The outcomes of selected tools are combined into a composite score (BORDASCORE) that exhibits a meaningful correlation with GDT_TS and facilitates the selection of optimal models in the absence of a reference structure. To validate AlphaMod's results, we conducted evaluations using two distinct datasets summing up to 72 targets, previously used to independently assess AlphaFold2's performance. The generated models underwent evaluation through two methods: i) averaging the GDT_TS scores across all produced structures for a single target sequence, and ii) a pairwise comparison of the best structures generated by AlphaFold2 and AlphaMod. The latter, within the unsupervised setups, shows a rising accuracy of approximately 34% over AlphaFold2. While, when considering the supervised setup, AlphaMod surpasses AlphaFold2 in 18% of the instances. Finally, there is an 11% correspondence in outcomes between the diverse methodologies. Consequently, AlphaMod's best-predicted tertiary structures in several cases exhibited a significant improvement in the accuracy of the predictions with respect to the best models obtained by AlphaFold2. This pipeline paves the way for the integration of additional data and AI-based algorithms to further improve the reliability of the predictions.

6-Bromo-pyridine-2-carbaldehyde phenyl-hydrazone.

The title compound, C(12)H(10)BrN(3), is essentially planar (r.m.s. deviation of all non-H atoms = 0.0174 Å), with a dihedral angle of 0.5 (2)° between the two aromatic rings. In the crystal, mol-ecules are linked by weak N-H⋯N inter-actions, forming a zigzag chain running parallel to [001].

1,4-Phenylenebis(methylene) bis(9H-carbazole-9-carbodithioate).

The molecules of the title compound, C(34)H(24)N(2)S(4), lie across centres of inversion in the space group P2(1)/n. The spacer unit linking the benzene rings and carbazole units is effectively planar, while the carbazole unit itself is slightly folded. Molecules are linked into sheets by a single C-H···π(arene) hydrogen bond and the hydrogen-bonded sheets are themselves linked into a three-dimensional framework structure by a single π-π stacking interaction.

2-Bromo-2-methyl-N-(4-nitro-phen-yl)propanamide.

The title compound, C(10)H(11)BrN(2)O(3), exhibits a small twist between the amide residue and benzene ring [the C-N-C-C torsion angle = 12.7 (4)°]. The crystal structure is stabilized by weak N-H⋯O, C-H⋯Br and C-H⋯O inter-actions. These lead to supra-molecular layers in the bc plane.

2-Bromo-N-(2-hy-droxy-5-methyl-phen-yl)-2-methyl-propanamide.

In the title mol-ecule, C(11)H(14)BrNO(2), there is twist between the mean plane of the amide group and the benzene ring [the C-N-C-C torsion angle is -172.1 (2)°]. The amide H atom forms an intra-molecular hydrogen bond with the Br atom. In the crystal, inter-molecular O-H⋯O and weak C-H⋯O hydrogen bonds link mol-ecules into a chain along [100].

2-Bromo-2-methyl-N-p-tolyl-propanamide.

In the title mol-ecule, C(11)H(14)BrNO, there is twist between the mean plane of the amide group and the benzene ring [C(=O)-N-C C torsion angle = -31.2 (5)°]. In the crystal, inter-molecular N-H⋯O and weak C-H⋯O hydrogen bonds link mol-ecules into chains along [100]. The methyl group H atoms are disordered over two sets of sites with equal occupancy.

2-Bromo-N-(4-chloro-phen-yl)-2-methyl-propanamide.

In the title mol-ecule, C(10)H(11)BrClNO, there is a twist between the mean plane of the amide group and the benzene ring [C(=O)-N-C-C torsion angle = -27.1 (3)°]. In the crystal, inter-molecular N-H⋯O and weak C-H⋯O hydrogen bonds link the mol-ecules into chains along [010].

Dataset on in-vitro study of chitosan-graphene oxide films for regenerative medicine.

Chitosan (CS) is well-known for its biological properties, especially its ability to induce tissue cicatrization. However, considerable research proved that CS presents a high inflammatory response and poor mechanical properties. For these reasons, we decided to use chitosan (CS) functionalized GO by a covalent bond (CS-GO). Due to the resistant structure of the GO and the high presence of oxygen functional groups on it, it will enhance the biocompatibility of the material. The data obtained in this investigation aimed to prove the possible application of CS-GO in regenerative medicine. For this reason, it was performed an In vitro analysis using brine shrimp to prove materials biocompatibility and gingival fibroblasts for a cell growth test.

Blind microscopy image denoising with a deep residual and multiscale encoder/decoder network.

In computer-aided diagnosis (CAD) focused on microscopy, denoising improves the quality of image analysis. In general, the accuracy of this process may depend both on the experience of the microscopist and on the equipment sensitivity and specificity. A medical image could be corrupted by several perturbations during image acquisition. Nowadays, CAD deep learning applications pre-process images with image denoising models to reinforce learning and prediction. In this work, an innovative and lightweight deep multiscale convolutional encoder-decoder neural network is proposed. Specifically, the encoder uses deterministic mapping to map features into a hidden representation. Then, the latent representation is rebuilt to generate the reconstructed denoised image. Residual learning strategies are used to improve and accelerate the training process using skip connections in bridging across convolutional and deconvolutional layers. The proposed model reaches on average 38.38 of PSNR and 0.98 of SSIM on a test set of 57458 images overcoming state-of-the-art models in the same application domain.Clinical relevance - Encoder-decoder based denoiser enables industry experts to provide more accurate and reliable medical interpretation and diagnosis in a variety of fields, from microscopy to surgery, with the benefit of real-time processing.

Synthesis and fabrication of films including graphene oxide functionalized with chitosan for regenerative medicine applications.

Graphene oxide (GO) has recently gained attention as a scaffold reinforcing agent for tissue engineering. Biomechanical and biological properties through a synergistic effect can be strengthened when combined with other materials such as chitosan (CS). For that reason, chitosan was used for Graphene Oxide (GO) functionalization through an amide group whose formation was evident by bands around 1600 cm-1 in the FTIR analysis. Furthermore, bands located at 1348 cm-1 (D band), 1593 cm-1 (G band), and 2416 cm-1 (2D band) in the RAMAN spectrum, and the displacement of the signal at 87.03 ppm (C5) in solid-state 13C-NMR confirmed the amide formation. Films including the CS-GO compound were prepared and characterized by thermogravimetric analysis (TGA), where CS-GO film presented a lighter mass loss (~10% less loosed) than CS due probably to the covalent functionalization with GO, providing film thermal resistance. The CS-GO films synthesized were implanted in Wistar rats' subdermal tissue as a first approximation to the biological response. In vivo tests showed a low inflammatory response, good cicatrization, and advanced resorption at 60 days of implantation, as indicated by histological images. It was evidenced that the covalent union between CS and GO increased biocompatibility and the degradation/resorption capacity, demonstrating tissue regeneration with typical characteristics and tiny remnants of implanted material surrounded by a type III collagen capsule. These results show the potential application of the new synthesized films, including the CS-GO compound, in tissue engineering.

2-{[(Dodecylsulfanyl)carbonothioyl]sulfanyl}-2-methylpropanoic acid: a chain of edge-fused R(2)(2)(8) and R(4)(4)(20) rings built from O-H...O and C-H...O hydrogen bonds.

In the title compound, C(17)H(32)O(2)S(3), the dodecyl chain and the trithiocarbonate unit adopt a nearly planar all-trans conformation, while the carboxyl group is synclinal to this chain direction. The molecules are linked by pairs of inversion-related O-H...O hydrogen bonds to form centrosymmetric dimers of R(2)(2)(8) type, and dimers related by translation are linked by C-H...O hydrogen bonds to form a chain of edge-fused rings, or a molecular ladder, containing alternating R(2)(2)(8) and R(4)(4)(20) rings.

2-(Phenyl-carbonothio-ylsulfan-yl)acetic acid.

The title compound, C(9)H(8)O(2)S(2), can be used as a chain transfer agent and may be used to control the behavior of polymerization reactions. O-H⋯O hydrogen bonds of moderate character link the mol-ecules into dimers. In the crystal, the dimers are linked into sheets by C-H⋯O inter-actions, forming R(4) (2)(12) and R(2) (2)(8) edge-fused rings running parallel to [101]. There are no inter-molecular inter-actions involving the S atoms.

Antimicrobial Films Based on Nanocomposites of Chitosan/Poly(vinyl alcohol)/Graphene Oxide for Biomedical Applications.

Today, tissue regeneration is one of the greatest challenges in the field of medicine, since it represents hope after accidents or illnesses. Tissue engineering is the science based on improving or restoring tissues and organs. In this work, five formulations of chitosan/poly(vinyl alcohol)/graphene oxide (CS/PVA/GO) nanocomposites were studied for the development of biodegradable films with potential biomedical applications. The characterization of the films consisted of Fourier-transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS). The antibacterial activity was evaluated in vitro against Gram-positive bacteria Bacillus cereus and Staphylococcus aureus and Gram-negative Salmonella spp. and Escherichia coli, by contact of the film above inoculum bacterial in Müeller⁻Hinton agar. On the other hand, in vivo tests in which the material implanted in the subcutaneous tissue of Wistar rats demonstrated that the formulation CS/PVA/GO (14.25:85:0.75) was the best antibacterial film with adequate degradation in vivo. All together, these results indicate the potential of the films using nanocomposites of CS/PVA/GO in tissue engineering and cell regeneration.

(E)-5-[1-Hy-droxy-3-(3,4,5-tri-meth-oxy-phen-yl)allyl-idene]-1,3-di-methyl-pyrimidine-2,4,6-trione: crystal structure and Hirshfeld surface analysis.

In the title compound, C18H20N2O7, the dihedral angle between the aromatic rings is 7.28 (7)° and the almost planar conformation of the mol-ecule is supported by an intra-molecular O-H⋯O hydrogen bond, which closes an S(6) ring. In the crystal, weak C-H⋯O hydrogen bonds and aromatic π-π stacking link the mol-ecules into a three-dimensional network. A Hirshfeld surface analysis showed that the major contribution to the inter-molecular inter-actions are van der Waals inter-actions (H⋯H contacts), accounting for 48.4% of the surface.

Electronic and electrochemical properties of grid-type metal ion complexes (Fe 2+ and Co 2+ ) with a pyridine-pyrimidine-pyridine based bis(hydrazone) / Propiedades electrónicas y electroquímicas de complejos metálicos (Fe 2+ y Co 2+ ) tipo rejilla con una bis(hidrazona) con estructura piridina-pirimidina-piridina) / Propriedades eletrônicas e eletroquímicas dos complexos metálicos (Fe 2+ e Co 2+ ) tipo grelha com uma bis(hidrazona) baseada em uma estrutura de piridina-pirimidina-piridina

Abstract The synthesis of new grid-type complexes of Co2+ and Fe2+ based on a highly soluble double hydrazone framework is reported. The data obtained from 1H NMR, FT-IR, and elemental analysis indicate that the complexes adopted a grid-like structure. Electronic properties of the metallogrids were analyzed by UV-Vis spectroscopy in chloroform, methanol, and dichloromethane. Additionally, cyclic voltammetry and square wave voltammetry were carried out in N,N-dimethylformamide (DMF). These compounds exhibited two oxidation processes corresponding to the organic ligand and several reductions events, comprising the ligand and metal centers. Furthermore, the interplay between the metal nature and the ligand framework was also studied in detail. These results represent an advancement in the chemistry of metallogrids not only because of the few reports concerning to the electrochemical properties found in the literature, but also for the design of novel hydrazone ligands of high solubility and easy preparation.

Resumen Se reporta la síntesis de nuevos complejos metálicos de Co2+ y Fe2+ tipo rejilla que contienen como ligando orgánico una doble hidrazona altamente soluble en solventes orgánicos. Los datos obtenidos de resonancia magnética nuclear (RMN 1H), espectroscopía infrarroja con transformada de Fourier (FT-IR) y análisis elemental indican que los complejos adoptaron una estructura de tipo rejilla. Las propiedades electrónicas de las metalo-rejillas fueron analizadas a través de espectroscopía UV-Vis en cloroformo, metanol y diclorometano. Adicionalmente, se realizaron medidas de voltamperometría cíclica y voltametría de onda cuadrada en DMF. Los complejos exhibieron dos procesos de oxidación atribuidos al ligando orgánico y a varios eventos reductivos que comprometían al ligando y a los centros metálicos, por tanto, la interacción entre la naturaleza del ion metálico y la estructura del ligando fue analizada en detalle. Estos resultados representan un avance en la química de metalo-rejillas no solo por los escasos reportes de propiedades electroquímicas encontrados en la literatura, sino también por el diseño de nuevos ligandos hidrazónicos de alta solubilidad y fácil preparación.

Resumo Neste trabalho relata-se a síntese de novos complexos de Co2+ e Fe2+ tipo grelha baseados na estrutura de uma hidrazona dupla altamente solúvel em solventes orgânicos. Os dados obtidos de ressonância magnética nuclear (1H RMN), espectroscopia de infravermelho com transformada de Fourier (FT-IR), e análise elementar indicam que os complexos adotaram a estrutura tipo grelha. As propriedades eletrônicas das grelhas metálicas foram analisadas por espectroscopia UV-Vis em clorofórmio, metanol e diclorometano. Adicionalmente, foram realizadas medidas de voltametria cíclica e voltametria de onda quadrada em DMF. Os compostos estudados exibiram dois processos de oxidação correspondentes ao ligando orgânico, e a vários eventos redutivos que envolvem o ligando orgânico e os centros metálicos. Além disso, a interação entre a natureza do metal e a estrutura do ligando foi estudada em detalhe. Estes resultados representam um avanço na química de metalo-grelhas não somente pelos escassos relatos de propriedades eletroquímicas encontrados na literatura, mas também pelo design de novos ligandos hidrazônicos de alta solubilidade e fácil preparação.

Structural, spectroscopic, and theoretical analysis of a molecular system based on 2-((2-(4-chlorophenylhydrazone) methyl)quinolone / Análisis estructural, espectroscópico y teórico de un sistema molecular basado en la 2-((2-(4-clorofenilhidrazono) metil)quinolina / Análise estrutural, espectroscópico, e teórico de um sistema molecular com base na 2-((2-(4-Clorofenilhidrazona) metil)quinolina

Abstract A novel molecular system based on 2-((2-(4-chlorophenylhydrazone)methyl)quinoline (1-E ) was synthesized. Interconversion of 1-E to its configurational isomer 1-Z was achieved using UV radiation (250 W Hg lamp). Such isomerization was monitored by ¹H-NMR. The results suggest that the hydrazone derivative can act as a chemical brake in solution. This molecular system was structurally (Single Crystal X-Ray diffraction and DFT calculations) and spectroscopically (NMR, UV, and IR) characterized. Electrochemical measurements showed that configurational changes induce differential redox behavior. In this regard, the reported quinoline system exhibits different dynamic absorption and electrochemical properties that are modulated by UV-light. Therefore, 1-E can be regarded as a potential photo-electrochemical switch.

Resumen Se sintetizó un nuevo sistema molecular basado en 2-((2-(4-chlorofenilhidrazona)metil)quinolina. Del mismo modo, se evaluó la respuesta dinámica de este compuesto a radiación ultravioleta y formación de un enlace de hidrógeno intramolecular. Los resultados muestran que este derivado de hidrazona puede actuar como freno en solución. El sistema en mención es descrito estructural (Cristalografía de Rayos X y cálculos DFT) y espectroscópicamente (RMN, UV e IR). La interconversión de este sistema entre las configuraciones 1-E y 1-Z fue mediada por radiación UV y monitoreada a través de RMN-¹H. El estudio electroquímico mostró un comportamiento diferencial en función de su configuración, aspecto fundamental en el desarrollo de sistemas foto- y electroquímicamente modulados.

Resumo Neste trabalho é apresentado um novo sistema molecular baseado na 2-((2-(4-clorofenilhidrazona)metil)quinolina, capaz de responder dinamicamente à radiação ultravioleta formando uma ligação de hidrogénio intramolecular que atua como um freio na solução. Este sistema é descrito estruturalmente (cristalografia de raios-X e DFT) e por diferentes técnicas espectroscópicas (RMN, de UV e de IV). Radiação UV foi usada para fazer a interconversão da hidrazona 1-E no seu isômero configuracional 1-Z . Este processo foi monitorado pelo RMN. As medidas eletroquímicas mostraram que as mudanças configuracionais entre os isômeros induzem a comportamentos redox diferentes, o que é uma caraterística chave no desenvolvimento de interruptores fotoelectroquímicos.

Acylhydrazone-based dynamic combinatorial libraries: study of the thermodynamic/kinetic evolution, configurational and coordination dynamics / Librerías combinatorias dinámicas basadas en acil-hidrazona: estudio del desarrollo termodinámico/cinético, dinámicas de configuración y de coordinación / Livrarias combinatórias dinâmicas baseadas na acil-hidrazona: estudo da evolução cinética/termodinâmica, dinâmicas de configuração e da coordenação

The kinetic and thermodynamic selectivity of acylhydrazone formation in dynamic combinatorial libraries (DCL) is described. Competition reactions were generated from hydrazides: isoniazid, 4-nitro-benzohydrazide, 4-dimethylamino-benzohydrazide, and nicotinic hydrazide as well as the aldehyde derivatives: benzaldehyde and 2-pyridine-carboxaldehyde. The obtained species and the distribution of the DCLs were monitored by 'H-NMR spectroscopy finding that those acylhydrazones containing the 4-dimethylamino-benzohydrazide moiety are both the kinetic and thermodynamic product of their respective libraries. Configurational and coordination dynamics for some of these libraries were also investigated. The obtained results allowed the study of the redistribution of components and the amplification of one or more products using light and metal ions as physical and chemical templates, respectively.

Se describe la selectividad cinética y termodinámica de la formación de acil-hidrazona en bibliotecas combinatorias dinámicas (DCL). Se generaron reacciones competitivas a partir de hidrazidas: isoniazida, 4-nitro-benzohidrazida, 4-dimetilamino-benzohidrazida y hidrazida nicotínica; así como a partir de los derivados de aldehído: benzaldehído y 2-piridin-carboxaldehido. Las especies obtenidas y la distribución de los DCLs fueron monitoreados mediante espectroscopia 'H-NMR, encontrándose que las acil-hidrazonas que contenían la 4-dimetilamino-benzohidrazida son tanto el producto cinético, como el termodinámico de sus respectivas bibliotecas. También se investigaron las dinámicas de configuración y de coordinación para algunas de estas bibliotecas. Los resultados obtenidos permitieron estudiar la redistribución de los componentes y la amplificación de uno o más productos usando luz e iones metálicos como plantillas físicas y químicas, respectivamente.

É descrita a seletividade cinética e termodinâmica da formação de acil-hidrazonas em livrarias combinatórias dinâmicas (DLC). Foram geradas reações competitivas a partir das hidrazidas: isoniazida, 4-nitro-benzohidrazida, 4-dimetilamino-benzohidrazida e hidrazida nicotínica; além dos derivados de aldeído: benzaldeído e 2-piridin-carboxaldeído. As espécies obtidas e a distribuição dos DLCs foram monitorados mediante espectroscopia 'H-NMR, foi encontrado que as acil-hidrazonas que continham à 4-dimetilamino-benzohidrazida são tanto o produto cinético como o termodinâmico de suas respectivas livrarias. Também investigaram-se as dinâmicas de configuração e coordenação para algumas destas livrarias. Os resultados obtidos permitem estudar a redistribuicao dos componentes e a amplificação de um ou mais produtos usando luz e íons metálicos como modelos físicos e químicos, respectivamente.