Manufacturing 3D Biomimetic Tissue: A Strategy Involving the Integration of Electrospun Nanofibers with a 3D-Printed Framework for Enhanced Tissue Regeneration.

3D printing and electrospinning are versatile techniques employed to produce 3D structures, such as scaffolds and ultrathin fibers, facilitating the creation of a cellular microenvironment in vitro. These two approaches operate on distinct working principles and utilize different polymeric materials to generate the desired structure. This review provides an extensive overview of these techniques and their potential roles in biomedical applications. Despite their potential role in fabricating complex structures, each technique has its own limitations. Electrospun fibers may have ambiguous geometry, while 3D-printed constructs may exhibit poor resolution with limited mechanical complexity. Consequently, the integration of electrospinning and 3D-printing methods may be explored to maximize the benefits and overcome the individual limitations of these techniques. This review highlights recent advancements in combined techniques for generating structures with controlled porosities on the micro-nano scale, leading to improved mechanical structural integrity. Collectively, these techniques also allow the fabrication of nature-inspired structures, contributing to a paradigm shift in research and technology. Finally, the review concludes by examining the advantages, disadvantages, and future outlooks of existing technologies in addressing challenges and exploring potential opportunities.

The mechanism of visible light-induced C-C cross-coupling by Csp3-H bond activation.

Csp3-C cross-coupling by activating Csp3-H bonds is a dream reaction for the chemical community, and visible light-induced transition metal-catalysis under mild reaction conditions is considered a powerful tool to achieve it. Advancement of this research area is still in its infancy because of the chemical and technical complexity of this catalysis. Mechanistic studies illuminating the operative reaction pathways can rationalize the increasing amount of experimental catalysis data and provide the knowledge allowing faster and rational advances in the field. This goal requires complementary experimental and theoretical mechanistic studies, as each of them is unfit to clarify the operative mechanisms alone. In this tutorial review we summarize representative experimental and computational mechanistic studies, highlighting weaknesses, strengths, and synergies between the two approaches.

Photoexcitation of Distinct Divalent Palladium Complexes in Cross-Coupling Amination Under Air.

The development of metal complexes that function as both photocatalyst and cross-coupling catalyst remains a challenging research topic. So far, progress has been shown in palladium(0) excited-state transition metal catalysis for the construction of carbon-carbon bonds where the oxidative addition of alkyl/aryl halides to zero-valent palladium (Pd0 ) is achievable at room temperature. In contrast, the analogous process with divalent palladium (PdII ) is uphill and endothermic. For the first time, we report that divalent palladium can act as a light-absorbing species that undergoes double excitation to realize carbon-nitrogen (C-N) cross-couplings under air. Differently substituted aryl halides can be applied in the mild, and selective cross-coupling amination using palladium acetate as both photocatalyst and cross-coupling catalyst at room temperature. Density functional theory studies supported by mechanistic investigations provide insight into the reaction mechanism.

Plant-Actuated Micro-Nanorobotics Platforms: Structural Designs, Functional Prospects, and Biomedical Applications.

Plants are anatomically and physiologically different from humans and animals; however, there are several possibilities to utilize the unique structures and physiological systems of plants and adapt them to new emerging technologies through a strategic biomimetic approach. Moreover, plants provide safe and sustainable results that can potentially solve the problem of mass-producing practical materials with hazardous and toxic side effects, particularly in the biomedical field, which requires high biocompatibility. In this review, it is investigated how micro-nanostructures available in plants (e.g., nanoparticles, nanofibers and their composites, nanoporous materials, and natural micromotors) are adapted and utilized in the design of suitable materials for a micro-nanorobot platform. How plants' work on micro- and nanoscale systems (e.g., surface roughness, osmotically induced movements such as nastic and tropic, and energy conversion and harvesting) that are unique to plants, can provide functionality on the platform and become further prospective resources are examined. Furthermore, implementation across organisms and fields, which is promising for future practical applications of the plant-actuated micro-nanorobot platform, especially on biomedical applications, is discussed. Finally, the challenges following its implementation in the micro-nanorobot platform are also presented to provide advanced adaptation in the future.

Monomeric Magnesium Catalyzed Alkene and Alkyne Hydroboration.

In this work, two monomeric magnesium alkyl complexes (1 and 2) were prepared using bis(phosphino)carbazole framework and among them 1 has been used as a catalyst for hydroboration of alkenes and alkynes with pinacolborane (HBpin). A broad variety of aromatic and aliphatic alkenes and alkynes were efficiently reduced. Anti-Markovnikov regioselective hydroboration of alkenes and alkynes was achieved, which was confirmed by deuterium-labelling experiments. The work represents the first example of the use of magnesium in homogeneous catalytic hydroboration of alkene with broad substrate scope. Experimental mechanistic investigations and DFT calculations provided insights into the reaction mechanism. Finally, the hydroboration protocol was extended to terpenes.

Performance of the nitrogen reduction reaction on metal bound g-C6N6: a combined approach of machine learning and DFT.

Developing a cost-effective and environmentally benign substitute for the energy-intensive Haber-Bosch process for the production of ammonia is a global challenge. The electrocatalytic nitrogen reduction reaction (NRR) under ambient conditions through the six proton-electron process has attracted significant interest. Herein, a series of transition-metal (TM) based single atom catalysts (SAC) embedded on carbon nitride (C6N6) have been chosen to explore the NRR activity. The promising metals have been primarily screened through density functional theory (DFT) by calculating their adsorption energies on C6N6 - energies for dinitrogen binding and the barriers at the rate determining step. Based on these criteria, amongst the 18 metal centers, Ta based C6N6 emerges as a good candidate for the reduction of nitrogen to NH3. On the other hand, for the Machine Learning (ML) regression models, the covalent radius and the d-band center of the TM have been identified as the most correlated descriptors for predicting the adsorption energy of nitrogen on the active metal center. Besides, probabilistic modeling using the soft voting technique in the classification model allows us to predict the most efficient single atom catalyst. Despite the realistic bottleneck of having only a limited number of TMs to choose from, this technique effectively predicts the best catalyst from a modest dataset. With the highest probabilistic score, Ta based C6N6 dominates over the other catalysts in a good agreement with DFT findings. This letter manifests the effectiveness of the soft voting technique in an ensemble-based classification model.

Palladium-Catalyzed para-C-H Arylation of Anilines with Aromatic Halides.

Controlling regioselectivity in C-H functionalizations is a key challenge in chemical method development. In arenes, functionalizations are most difficult to direct towards the C-H group furthest away from a substituent, in its para position. We herein demonstrate how the para-C-H arylation of anilines with non-activated aryl halides, elusive to date, is achieved by a base-assisted "metalla-tautomerism" approach. A proton is abstracted from the aniline substrate and replaced by an arylpalladium species, generated from the aryl halide coupling partner. In this step, the palladium is directed away from the N- to the tautomeric para-C-H position by a large phosphine ligand combined with a triphenylmethyl shielding group. The triphenylmethyl group is easily installed and removed, and can be recycled.

Germyliumylidene: A Versatile Low Valent Group 14 Catalyst.

Bis-NHC stabilized germyliumylidenes [RGe(NHC)2 ]+ are typically Lewis basic (LB) in nature, owing to their lone pair and coordination of two NHCs to the vacant p-orbitals of the germanium center. However, they can also show Lewis acidity (LA) via Ge-CNHC σ* orbital. Utilizing this unique electronic feature, we report the first example of bis-NHC-stabilized germyliumylidene [Mes TerGe(NHC)2 ]Cl (1), (Mes Ter=2,6-(2,4,6-Me3 C6 H2 )2 C6 H3 ; NHC= IMe4 =1,3,4,5-tetramethylimidazol-2-ylidene) catalyzed reduction of CO2 with amines and arylsilane, which proceeds via its Lewis basic nature. In contrast, the Lewis acid nature of 1 is utilized in the catalyzed hydroboration and cyanosilylation of carbonyls, thus highlighting the versatile ambiphilic nature of bis-NHC stabilized germyliumylidenes.

Si(II) Cation-Promoted Formation of an Abnormal NHC-Bound Silylene and a cAAC-Silanyl Radical Ion.

The reaction of amidinatosilylene LSi(:)Cl [L = PhC(NtBu)2] with N-heterocyclic carbene IAr [:C{N(Ar)CH}2, where Ar = 2,6-iPr2C6H3] and NaOTf in tetrahydrofuran (THF) facilely afforded a silicon(II) cation [LSi(:)-aIAr]+OTf- (1+OTf-), where IAr isomerizes to abnormal N-heterocyclic carbene aIAr, coordinating to the silicon(II) center. Its Ge homologue, [LGe(:)-aIAr]+OTf- (2+OTf-), was also accessed via the same protocol. For the formation of 1+, we propose that an in situ-generated Si(II) cation [LSi(:)]+ under the treatment of LSi(:)Cl with NaOTf may isomerize IAr in THF. In contrast, the replacement of IAr with cyclic alkyl(amino) carbene (cAAC) furnished a cAAC-silanyl radical ion [LSi(H)-cAAC]•+(LiOTf2)- [3•+(LiOTf2)-], which may undergo an abstraction of the H radical from THF. All of the products were characterized by nuclear magnetic resonance spectroscopy, electron paramagnetic resonance, and X-ray crystallography, and their bonding scenarios were investigated by density functional theory calculations. These studies provide new perspective on carbene-silicon chemistry.

Mushroom-Derived Bioactive Molecules as Immunotherapeutic Agents: A Review.

Mushrooms with enhanced medicinal properties focus on finding such compounds that could modulate the human body's immune systems. Mushrooms have antimicrobial, antidiabetic, antiviral, hepatoprotective, antitumor, and immunomodulatory properties due to the presence of various bioactive components. ß-glucans are the major constituent of the mushroom cell wall and play a significant role in their biological activity. This review described the techniques used in the extraction of the active ingredients from the mushroom. We highlighted the structure of the bioactive polysaccharides present in the mushrooms. Therapeutic applications of different mushrooms were also described. It is interesting to note that mushrooms have the potential sources of many bioactive products that can regulate immunity. Thus, the development of functional medicinal food based on the mushroom is vital for human welfare.

Graphene Oxide-Based Stimuli-Responsive Platforms for Biomedical Applications.

Graphene is a two-dimensional sp2 hybridized carbon material that has attracted tremendous attention for its stimuli-responsive applications, owing to its high surface area and excellent electrical, optical, thermal, and mechanical properties. The physicochemical properties of graphene can be tuned by surface functionalization. The biomedical field pays special attention to stimuli-responsive materials due to their responsive abilities under different conditions. Stimuli-responsive materials exhibit great potential in changing their behavior upon exposure to external or internal factors, such as pH, light, electric field, magnetic field, and temperature. Graphene-based materials, particularly graphene oxide (GO), have been widely used in stimuli-responsive applications due to their superior biocompatibility compared to other forms of graphene. GO has been commonly utilized in tissue engineering, bioimaging, biosensing, cancer therapy, and drug delivery. GO-based stimuli-responsive platforms for wound healing applications have not yet been fully explored. This review describes the effects of different stimuli-responsive factors, such as pH, light, temperature, and magnetic and electric fields on GO-based materials and their applications. The wound healing applications of GO-based materials is extensively discussed with cancer therapy and drug delivery.

N-Heterocyclic Carbene-Stabilized Germa-acylium Ion: Reactivity and Utility in Catalytic CO2 Functionalizations.

The first acceptor-free heavier germanium analogue of an acylium ion, [RGe(O)(NHC)2]X (R = MesTer = 2,6-(2,4,6-Me3C6H2)2C6H3; NHC = IMe4 = 1,3,4,5-tetramethylimidazol-2-ylidene; X = (Cl or BArF = {(3,5-(CF3)2C6H5)4B}), was isolated by reacting [RGe(NHC)2]X with N2O. Conversion of the germa-acylium ion to the first solely donor-stabilized germanium ester [(NHC)RGe(O)(OSiPh3)] and corresponding heavier analogues ([RGe(S)(NHC)2]X and [RGe(Se)(NHC)2]X) demonstrated its classical acylium-like behavior. The polarized terminal GeO bond in the germa-acylium ion was utilized to activate CO2 and silane, with the former found to be an example of reversible activation of CO2, thus mimicking the behavior of transition metal oxides. Furthermore, its transition-metal-like nature is demonstrated as it was found to be an active catalyst in both CO2 hydrosilylation and reductive N-functionalization of amines using CO2 as the C1 source. Mechanistic studies were undertaken both experimentally and computationally, which revealed that the reaction proceeds via an N-heterocyclic carbene (NHC) siloxygermylene [(NHC)RGe(OSiHPh2)].

Cyclic (Alkyl)(Amino)Carbene-Stabilized Aluminum and Gallium Radicals Based on Amidinate Scaffolds.

Neutral, mononuclear aluminum and gallium radicals, stabilized by cyclic (alkyl)(amino)carbene (cAAC), were synthesized. LMCl2 upon reduction with KC8 in the presence of cAAC afforded the radicals LMCl(cAAC), where L = PhC(NtBu)2 and M = Al (1), Ga (2). The radicals were characterized by X-ray crystallography, electron paramagnetic resonance (EPR) spectroscopy, and mass spectrometry. EPR, SQUID measurement, and computational calculations confirmed paramagnetism of the radicals with unpaired spin mainly on cAAC.

Protaetia brevitarsis seulensis Derived Protein Isolate with Enhanced Osteomodulatory and Antioxidative Property.

The osteogenic differentiation of stem cells is profoundly affected by their microenvironmental conditions. The differentiation behavior of stem cells can be tuned by changing the niche environments. The proteins or peptides that are derived by living organisms facilitate the osteogenic differentiation of stem cells. Here, we have evaluated the osteoinductive and antioxidative potential of the Protaetia brevitarsis seulensis insect-derived protein for human bone marrow-derived mesenchymal stem cells (hBMSCs). The amino acid contents in the isolated protein were determined by an amino acid analyzer. Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM) were used to analyze the extract's functional groups and surface morphology. The extracted protein exhibited 51.08% ß-sheet conformation. No adverse effects were observed in extract-treated cells, indicating their biocompatibility. The protein isolate showed an excellent antioxidative property. Besides this, an enhancement in the hBMSCs' mineralization has been observed in the presence of treated protein isolates. Notably, osteogenic marker genes and proteins were effectively expressed in the treated cells. These results indicated that the P. brevitarsis-derived protein isolate can be used as a potential antioxidative biomaterial for bone tissue engineering applications.

Computational Exploration of Mechanistic Avenues in C-H Activation Assisted Pd-Catalyzed Carbonylative Coupling.

The detailed mechanism of the intermolecular Pd-catalyzed carbonylative coupling reaction between aryl bromides and polyfluoroarenes relying on C(sp2)-H activation was investigated using state-of-the-art computational methods (SMD-B3LYP-D3(BJ)/BS2//B3LYP-D3/BS1). The mechanism unveils the necessary and important roles of a slight excess of carbon monoxide: acting as a ligand in the active catalyst state, participating as a reactant in the carbonylation process, and accelerating the final reductive elimination event. Importantly, the desired carbonylative coupling route follows the rate-limiting C-H activation process via the concerted metalation-deprotonation pathway, which is slightly more feasible than the decarboxylative route leading to byproduct formation by 1.2 kcal/mol. The analyses of the free energies indicate that the choice of base has a significant effect on the reaction mechanism and its energetics. The Cs2CO3 base guides the reaction toward the coupling route, whereas carbonate bases such as K2CO3 and Na2CO3 switch toward an undesired decarboxylative path. However, K3PO4 significantly reduces the C-H activation barrier over the decarboxylation reaction barrier and can act as a potential alternative base. The positional influence of a methoxy substituent in bromoanisole and different substituent effects in polyfluoroarenes were also considered. Our results show that different substituents impose significant impact on the desired carbonylative product formation energetics. Considering the influence of several ligands leads to the conclusion that other phosphine and N-heterocyclic carbene, such as P nBuAd2 and IMes, can be used as an efficient alternative than the experimentally reported P tBu3 ligand exhibiting a clear preference for C-H activation (ΔΔ⧧ GLS) by 7.1 and 10.9 kcal/mol, respectively. We have also utilized the energetic span model to interpret the experimental results. Moreover, to elucidate the origin of activation barriers, energy decomposition analysis calculations were accomplished for the critical transition states populating the energy profiles.

Donor Stabilized Diatomic Gr.14 E2 (E = C-Pb) Molecule D-E2-D (D = NHC, aNHC, NNHC, NHSi, NHGe, cAAC, cAASi, cAAGe): A Theoretical Insight.

Quantum chemical calculations have been carried out to explore the detailed electronic structure and bonding scenario in various bis-donor stabilized E2 compounds (E = C-Pb). Our computational findings reveal that the thermodynamic stabilities of the E2 core gradually decrease as we move down the group. A linear D-E-E'-D framework is observed for C2 systems, while the heavier group 14 analogues possess trans-bent geometries. Consideration of few compounds as viable targets for synthesis is suggested by their corresponding calculated formation energies. In addition, the thermodynamic stabilities of C2 systems notably increase with the saturation of the donor ring framework and are even more pronounced for boron-substituted saturated NHD ligand. QTAIM calculations affirmed that the covalent nature of E-E' bonds shifts toward the donor-acceptor region as one traverses from top to bottom along group 14. The E-D and E'-D bonds in the C2 systems have covalent nature, whereas those in Si2-Pb2 systems are characterized by donor-acceptor bonds. In addition, we have computed proton affinities and vertical ionization potentials (VIPs) of these compounds. An excellent correlation was obtained between calculated VIPs and orbital energies of HOMOs. Furthermore, in the present study, we also explored the effect of bis-donors in the stabilization of heterodiatomic SiC compounds. Our calculations indicate that a typical bonding description of the SiC(D)2 compounds should be represented by a combination of a classical double bond between C-D with significant donor-acceptor interaction in Si-D, i.e., D → Si═C═D. The SiC(D)2 systems are found to be less stable than the corresponding dicarbon compounds C2(D)2, but they show significant stabilization compared to the corresponding disilicon systems Si2(D)2.

Mechanistic Exploration of the Transmetalation and Reductive Elimination Events Involving PdIV -Abnormal NHC Complexes in Suzuki-Miyaura Coupling Reactions: A DFT Study.

A comprehensive DFT (M06-L-D3(SMD)/BS2//M06-L/BS1 level) investigation has been carried out to explore in detail the mechanism of the transmetalation and reductive elimination reactions of abnormal N-heterocyclic carbene (aNHC) palladium(IV) complexes within the framework of Suzuki-Miyaura cross-coupling reactions. Emphasis was placed on the role of base and the effect of countercations on the critical transmetalation and reductive elimination events involving palladium(IV) complexes. Of the two competing roles of the base, the route involving boronate formation followed by halide exchange prevails over that of direct halide exchange for the intermediates [PdIV (aNHC)(OMe)2 Cl]- Na+ (pathway A), [PdIV (aNHC)(OMe)(Cl)2 ]- Na+ (pathway B), and [PdIV (aNHC)Cl3 ]- Na+ (pathway C) emanating from the oxidative addition reaction. The results of the calculations are in accordance with our previous theoretical findings of favorable energetics for palladium intermediates incorporating two coordinated methoxy groups. The negative role played by the countercation in the transmetalation step is mainly due to the overstabilization of the pre-transmetalation intermediate, which is in line with experimental kinetic results. The anionic complexes exhibit greater affinity for the transmetalation and reductive elimination reactions than the neutral variants.

Computational Investigation of Carbene-Phosphinidenes: Correlation between 31P Chemical Shifts and Bonding Features to Estimate the π-Backdonation of Carbenes.

Detailed investigations of the electronic structure and bonding scenario in different carbene-phosphinidenes have been presented using state-of-the-art computational methods (BP86/def2-TZVPP//BP86/def2-SVP). We have endeavored to find the correlation of the calculated 31P chemical shifts with different bonding parameters of compounds to access the relative π-acceptor strengths of the carbenes. 31P chemical shifts exhibit a weak correlation with σ-polarizations of Ccarb-P bonds toward phosphorus; however excellent correlations are obtained in the case of π-polarizations of Ccarb-P bonds toward the carbene carbon (Ccarb) and NPA charges on phosphorus atoms. 31P chemical shifts also show excellent correlations with the electron densities and energy densities of Ccarb-P bonds at BCPs, as suggested by QTAIM calculations. Moreover, EDA-NOCV analysis is implemented to gain brief insight into the bonding scenario in this class of compounds. Good correlation exists between the interaction energies between the carbene and PPh fragments and 31P chemical shifts. Additionally, we have investigated the correlations of calculated 31P chemical shifts with different bonding parameters of the corresponding free carbenes. The bonding scenario in different carbene-substituted phosphinidenes is also explored to see how the bonding situation depends on various substituents on phosphinidenes. The other substituted carbene-phosphinidenes show correlations similar to those of carbene-phenylphosphinidenes.

Silanylidene and Germanylidene Anions: Valence-Isoelectronic Species to the Well-Studied Phosphinidene.

The reduction of TipMCl3 (Tip=2,4,6-triisopropylphenyl) (M=Si, Ge) with KC8 in the presence of cyclic alkyl(amino) carbene (cAAC) afforded the acyclic silanylidene and germanylidene anions in the form of potassium salt [K(cAAC)MTip]2 (M=Si (1); Ge (2)). The silanylidene and germanylidene anions are valence-isoelectronic to the well-studied phosphinidene and are a new class of acyclic anions of Group 14. Compounds 1 and 2 were isolated and well characterized by NMR and single-crystal X-ray structure analysis. Furthermore, the structure and bonding of compounds 1 and 2 was investigated by computational methods.

Two Structurally Characterized Conformational Isomers with Different C-P Bonds.

The cyclic alkyl(amino) carbene (cAAC) bonded chlorophosphinidene (cAAC)P-Cl (2/2') was isolated from the direct reaction between cAAC and phosphorus trichloride (PCl3 ). Compound 2/2' has been characterized by NMR spectroscopy and mass spectrometry. 31 P NMR investigations [δ≈160 ppm (major) and δ≈130 ppm (minor)] reveal that there are two different P environments of the P-Cl unit. X-ray single-crystal determination suggests a co-crystallization of two conformational isomers of (cAAC)P-Cl (2/2'); the major compound possessing a cAAC-PCl unit with CcAAC -P 1.75 Å. This C-P bond length is very close to that of (NHC)2 P2 [NHC=N-heterocyclic carbene]. The residual density can be interpreted as a conformational isomer with a shorter CcAAC -P bond similar to a non-conjugated phosphaalkene [R-P=CR2 ]. Our study shows an unprecedented example of two conformational isomers with different Ccarbene -element bonds. Additionally, Br (3c/3c'), I (4c/4c'), and H (5c/5c') analogues [(Me2 -cAAC)P-X; X=Br (3), I (4), H (5)] of 2c/2c'[(Me2 -cAAC)P-Cl] were also synthesized and characterized by NMR spectroscopy suggesting similar equilibrium in solution. The unique property of cAAC and the required electronegativity of the X (X=Cl, Br, I, and H) atom play a crucial role for the existence of the two isomers which were further studied by theoretical calculations.