Phenyllithium Research Articles

Development of Biphasic Injectable Hydrogels for Meniscus Scaffold from Photocrosslinked Glycidyl Methacrylate-Modified Poly(Vinyl Alcohol)/Glycidyl Methacrylate-Modified Silk Fibroin.

The development of a hydrogel material with a modified chemical structure of poly(vinyl alcohol) (PVA) and silk fibroin (SF) using glycidyl methacrylate (GMA) (denoted as PVA-g-GMA and SF-g-GMA) is an innovative approach in the field of biomaterials and meniscus tissue engineering in this study. The PVA-g-GMA/SF-g-GMA hydrogel was fabricated using different ratios of PVA-g-GMA to SF-g-GMA: 100/0, 75/25, 50/50, 25/75, and 0/100 (w/w of dry substances), using lithium phenyl (2,4,6-trimethylbenzoyl)phosphinate (LAP) as a free radical photoinitiator, for 10 min at a low ultraviolet (UV) intensity (365 nm, 6 mW/cm2). The mechanical properties, morphology, pore size, and biodegradability of the PVA-g-GMA/SF-g-GMA hydrogel were investigated. Finally, for clinical application, human chondrocyte cell lines (HCPCs) were mixed into PVA-g-GMA/SF-g-GMA solutions and fabricated into hydrogel to study the viability of live and dead cells and gene expression. The results indicate that as the SF-g-GMA content increased, the compressive modulus of the PVA-g-GMA/SF-g-GMA hydrogel dropped from approximately 173 to 11 kPa. The degradation rates of PVA-g-GMA/SF-g-GMA 100/0, 75/25, and 50/50 reached up to 15.61%, 17.23%, and 18.93% in 4 months, respectively. In all PVA-g-GMA/SF-g-GMA conditions on day 7, chondrocyte cell vitality exceeded 80%. The PVA-g-GMA/SF-g-GMA 75:25 and 50:50 hydrogels hold promise as a biomimetic biphasic injectable hydrogel for encapsulated augmentation, offering advantages in terms of rapid photocurability, tunable mechanical properties, favorable biological responses, and controlled degradation.

Synthesis of Fluoromethyl‐substituted Cyclopropanes by Electrophilic Cyclization of Homoallylic Boronate Intermediates

The electrophilic cyclization via the boronate complex between various homoallylic boronates and Selectfluor® is reported. This reaction provides a fluoromethylated cyclopropane ring that was difficult to synthesize by previous methods. The use of phenyl lithium, which activates the homoallylic boronate, is important for the reaction. The intermediate boronate species in this reaction was observed through <sup>11</sup>B NMR experiments. We also demonstrate the synthesis of a building block including fluoromethyl‐substituted cyclopropane for a bioactive compound.

Activation of Bulk Li2S as Cathode Material for Lithium‐Sulfur Batteries through Organochalcogenide‐Based Redox Mediation Chemistry

AbstractLithium sulfide (Li2S) is considered as a promising cathode material for sulfur‐based batteries. However, its activation remains to be one of the key challenges against its commercialization. The extraction of Li+ from bulk Li2S has a high activation energy (Ea) barrier, which is fundamentally responsible for the initial large overpotential. Herein, a systematic investigation of accelerated bulk Li2S oxidation reaction kinetics was studied by using organochalcogenide‐based redox mediators, in which phenyl ditelluride (PDTe) can significantly reduce the Ea of Li2S and lower the initial charge potential. Simultaneously, it can alleviate the polysulfides shuttling effect by covalently anchoring the soluble polysulfides and converting them into insoluble lithium phenyl tellusulfides (PhTe‐SxLi, x>1). This alters the redox pathway and accelerates the reaction kinetics of Li2S cathode. Consequently, the Li||Li2S‐PDTe cell shows excellent rate capability and enhanced cycling stability. The Si||Li2S‐PDTe full cell delivers a considerable capacity of 953.5 mAh g−1 at 0.2 C.

Activation of Bulk Li2S as Cathode Material for Lithium-Sulfur Batteries through Organochalcogenide-Based Redox Mediation Chemistry.

Lithium sulfide (Li2S) is considered as a promising cathode material for sulfur-based batteries. However, its activation remains to be one of the key challenges against its commercialization. The extraction of Li+ from bulk Li2S has a high activation energy (Ea) barrier, which is fundamentally responsible for the initial large overpotential. Herein, a systematic investigation of accelerated bulk Li2S oxidation reaction kinetics was studied by using organochalcogenide-based redox mediators, in which phenyl ditelluride (PDTe) can significantly reduce the Ea of Li2S and lower the initial charge potential. Simultaneously, it can alleviate the polysulfides shuttling effect by covalently anchoring the soluble polysulfides and converting them into insoluble lithium phenyl tellusulfides (PhTe-SxLi, x > 1). This alters the redox pathway and accelerates the reaction kinetics of Li2S cathode. Consequently, the Li||Li2S-PDTe cell shows excellent rate capability and enhanced cycling stability. The Si||Li2S-PDTe full cell delivers a considerable capacity of 953.5 mAh g-1 at 0.2 C.

Synthesis of biocompatible BSA-GMA and two-photon polymerization of 3D hydrogels with free radical type I photoinitiator.

Although the development of three-dimensional (3D) printing technology is growing rapidly in the biomedical field, it remains a challenge to achieve arbitrary 3D structures with high resolution and high efficiency. Protein hydrogels fabricated by two- photon polymerization (TPP) have excellent mechanical properties, high precision, and 3D architecture. However, a large number of the amino acid group in bovine serum albumin (BSA) would be consumed when the protein-based hydrogels use dyes of free radical type II photoinitiators. In this study, we use glycidyl methacrylate (GMA) to modify BSA molecules to obtain a series of BSA-GMA materials, allowing the protein material to be two-photon polymerized with a water-soluble free radical type I photoinitiator. The precisely controllable 3D structure of the BSA-GMA hydrogel was fabricated by adjusting the concentration of the precursor solution, the degree of methacrylation, and the processing parameters of the TPP technique. Importantly, BSA-GMA materials are free of acidic hazardous substances. Meanwhile, the water-soluble initiator lithium phenyl (2,4,6-trimethylbenzoyl) phosphite (LAP) allows TPP on the vinyl group of the GMA chain and thus without consuming its amino acid group. The as-prepared BSA-GMA hydrogel structure exhibits excellent autofluorescence imaging, pH responsiveness, and biocompatibility, which would provide new avenues for potential applications in tissue engineering and biomedical fields to meet specific biological requirements.

Biphasic burst and sustained transdermal delivery in vivo using an AI-optimized 3D-printed MN patch

The objective of the present study was to fabricate microneedles for delivering lipophilic active ingredients (APIs) using digital light processing (DLP) printing technology and quality by design (QbD) supplemented by artificial intelligence (AI) algorithms. In the present study, dissolvable microneedle (MN) patches using ibuprofen (IBU) as a model drug were successfully fabricated with DLP printing technology at ∼ 750 μm height, ∼250 μm base diameter, and tip with radius of curvature (RoC) of ∼ 15 μm. MN patches were comprised of IBU, photoinitiator, Lithium phenyl (2,4,6-trimethylbenzoyl) phosphinate (LAP), polyethylene glycol dimethacrylate (PEGDAMA)550 and distilled water and were developed using the QbD optimization approach. Optimization of print fidelity and needle morphology were achieved using AI implementing a semi-supervised machine learning approach. Mechanical strength tests demonstrated that IBU MNs formed pores both on Parafilm M® and human cadaver skin. IBU-MNs consisting of 0.23 %w/v and 0.49 %w/v LAP with 10 %w/v water showed ∼ 2 mg/cm2 sustained drug permeation at 72 h in skin permeation experiments with flux of ∼ 40 μg/cm2/h. Pharmacokinetic studies in rats displayed biphasic rapid first-order absorption with sustained zero-order input of Ko = 150ug/hr, AUC0-48h = 62812.02 ± 11128.39 ng/ml*h, Tmax = 2.66 ± 1.12 h, and Cmax = 3717.43 ± 782.25 ng/ml (using 0.23 %w/v LAP IBU MN patch). An in vitro in vivo relation (IVIVR) was conducted identifying a polynomial relationship between patch release and fraction absorbed in vivo. This study demonstrates fabrication of dissolvable DLP-printed microneedle patches for lipophilic API delivery with biphasic rapid first-order and sustained zero-order release.

Tomographic volumetric bioprinting of heterocellular bone-like tissues in seconds.

Tomographic volumetric bioprinting (VBP) has recently emerged as a powerful tool for rapid solidification of cell-laden hydrogel constructs within seconds. However, its practical applications in tissue engineering requires a detailed understanding of how different printing parameters (concentration of resins, laser dose) affect cell activity and tissue formation. Herein, we explore a new application of VBP in bone tissue engineering by merging a soft gelatin methacryloyl (GelMA) bioresin (<5kPa) with 3D endothelial co-culture to generate heterocellular bone-like constructs with enhanced functionality. To this, a series of bioresins with varying concentrations of GelMA and lithium Phenyl(2,4,6-trimethylbenzoyl)phosphinate (LAP) photoinitiator were formulated and characterized in terms of photo-reactivity, printability and cell-compatibility. A bioresin with 5% GelMA and 0.05% LAP was identified as the optimal formulation for VBP of complex perfusable constructs within 30s at high cell viability (>90%). The fidelity was validated by micro-computed tomography and confocal microscopy. Compared to 10% GelMA, this bioresin provided a softer and more permissive environment for osteogenic differentiation of human mesenchymal stem cells (hMSCs). The expression of osteoblastic markers (collagen-I, ALP, osteocalcin) and osteocytic markers (podoplanin, Dmp1) was monitored for 42 days. After 21 days, early osteocytic markers were significantly increased in 3D co-cultures of hMSCs with human umbilical vein endothelial cells (HUVECs). Additionally, we demonstrate VBP of a perfusable, pre-vascularized model where HUVECs self-organized into an endothelium-lined channel. Altogether, this work leverages the benefits of VBP and 3D co-culture, offering a promising platform for fast scaled biofabrication of 3D bone-like tissues with unprecedented functionality. STATEMENT OF SIGNIFICANCE: This study explores new strategies for ultrafast bio-manufacturing of bone tissue models by leveraging the advantages of tomographic volumetric bioprinting (VBP) and endothelial co-culture. After screening the properties of a series of photocurable gelatin methacryloyl (GelMA) bioresins, a formulation with 5% GelMA was identified with optimal printability and permissiveness for osteogenic differentiation of human mesenchymal stem cells (hMSC). We then established 3D endothelial co-cultures to test if the heterocellular interactions may enhance the osteogenic differentiation in the printed environments. This hypothesis was evidenced by increased gene expression of early osteocytic markers in 3D co-cultures after 21 days. Finally, VBP of a perfusable cell-laden tissue construct is demonstrated for future applications in vascularized tissue engineering.

Topology crafting of polyvinylidene difluoride electrolyte creates ultra-long cycling high-voltage lithium metal solid-state batteries

Solid-state polymer electrolytes (SPEs) present poor anti-oxidation ability, low ionic conductivity and high flammability, which greatly restrict their applications in high-voltage solid-state lithium metal batteries. Herein, we uniformly graft the lithium phenyl phosphate (LPPO) on polyvinylidene difluoride (PVDF) by dehydrofluorination and Friedel-Crafts alkylation reactions to create a multifunctional PVDF-LPPO SPE with branched topology. The LPPO serves as a single ion conductor, flame retardant and cathode electrolyte interface formation agent not only greatly improves the ionic conductivity, fireproof property and electrochemical stability of SPE, but also remarkably suppresses the side reactions with both cathode and lithium metal anode. An additional and uniform Li-ion transmission path is constructed by LPPO to remarkably reduce the activation energy and enhance the lithium-ion transference number of PVDF-LPPO SPE. The solid-state LiNi0.8Co0.1Mn0.1O2||PVDF-LPPO||Li batteries stably cycle for 1550 times between 2.8 and 4.3 V at 1 C and 1000 times under a high charging voltage of 4.5 V. The transformation of layered structure to rock-salt phase of NCM811 particles is greatly suppressed during long cycling by a stable and uniform LPPO derived cathode electrolyte interface. This work provides a precise operation method for modifying structure of polymer electrolyte to achieve outstanding special properties of lithium metal solid-state batteries.

Retrofitting of an Affordable 3D Printer: Towards a Material Efficient and Low-Cost Bioprinting System

3D bioprinting is an emerging technique employed for engineering complex structures that can be used for regenerative medicine. Extrusion of hydrogels through a nozzle has produced layer by layer designs towards engineering patterns. Despite the significant advances of these systems in the biomedical field, there are some inherent constraints to achieve higher resolutions without impacting the viability of the cells contained in the bioinks. Recently, there has been research on polymerization using light and photosensitive materials that point toward finer details within more reproducible manufacturing conditions and more complex products. Recent advances in bioprinting include the implementation of the construction of multimaterial structures to mimic in a more precise way a complex tissue. This paper showcases the development of a novel design using a retrofitting strategy toward a Material Efficient and Low-Cost Bioprinting system based on a Liquid Crystal Display (LCD) technique that reduces the required materials with a low-volume material reservoir and optimizes the processing parameters. Towards a new generation of devices, we present a novel open-source retrofitting kit for adapting a low-cost commercially available Anycubic 3D printer to process a bioink. As a proof-of-concept, an initial study of the concentration of gelatin methacryloyl (GelMa) and Lithium Phenyl -2, 4, 6 -trimethylbenzoylphosphinate (LAP) photoinitiator and the manufacturability is hereby presented for hexagonal, circular, and square features. The design of a new setup enabled a reduction of 90% of the required bioink. While further research is required to validate this concept, this is a step towards a new generation of affordable bioprinting systems.

An Organotin Route for the Preparation of 2,6‐Bis(diphenylphosphino)bromo‐benzene and the Related Bis(Phosphine Oxide). Precursors for Novel Ligands

AbstractThe 2,6‐difluorophenyltrialkylstannanes 2,6‐F2C6H3SnR3 (1, R=Me; 2, R=Bu) were prepared from commercial products. With Ph2PLi, 1 and 2 underwent nucleophilic substitution to give the 2,6‐bis(diphenylphosphino)phenyltrialkylstannanes 2,6‐(Ph2P)2C6H3SnR3 (3, R=Me; 4, R=Bu). The reaction of 3 with n‐BuLi and BrCH2CH2Br afforded 2,6‐bis(diphenylphosphino)bromobenzene (2,6‐(Ph2P)2C6H3Br, 5), the oxidation of which gave the related bis(phosphine oxide) 2,6‐[Ph2P(O)]2C6H3Br (6). The reaction of 5 with n‐BuLi gave rise to the formation of 2,6‐bis(diphenylphosphino)phenyl lithium, 2,6‐(Ph2P)2C6H3Li (7). Attempts to prepare the related bis(phosphine oxide) 2,6‐[Ph2P(O)]2C6H3Li (8) from 6 in a similar way at low temperatures was hampered by decomposition. Compounds 3, 5 and 7 hold potential for a new anionic tridentate PCP−coordinating ligand, namely, the bis(2,6‐diphenyl)phosphinophenyl ion [2,6‐(Ph2P)2C6H3]−.

Phenyl argentate aggregates [AgnPhn+1]- (n = 2-8): Models for the self-assembly of atom-precise polynuclear organometallics.

Electrospray ionization of phenyl argentates formed by transmetalation reactions between phenyl lithium and silver cyanide provides access to the argentate aggregates, [AgnPhn+1]-, which were individually mass-selected for n = 2-8 in order to generate their gas-phase Ultraviolet Photodissociation (UVPD) "action" spectra over the range 304-399nm. A strong bathochromic shift in optical spectra was observed with increasing size/n. Theoretical calculations allowed the assignment of the experimental UVPD spectra to specific isomer(s) and provided crucial insights into the transition from the 2D to 3D structure of the metallic component with the increasing size of the complex. The [AgnPhn+1]- aggregates contain neither pronounced metallic cluster properties nor ligated metallic cluster features and are thus not superatom complexes. They therefore represent novel organometallic characteristics built from Ag2Ph subunits.

Methacrylated pullulan/polyethylene (glycol) diacrylate composite hydrogel for cartilage tissue engineering

Pullulan hydrogels are widely used in tissue engineering and drug delivery. However, these hydrogels do not meet the requirements of articular cartilage repair because of their fast degradation rate and poor mechanical strength. Herein, we fabricated a hybrid hydrogel system by combining pullulan with synthetic polymers polyethylene (glycol) diacrylate (PEGDA). In this study, pullulan was modified with methacrylic anhydride (MA) to obtain photo-crosslinkable methacrylated pullulan (PulMA). Moreover, the lithium phenyl(2,4,6-trimethylbenzoyl)phosphinate (LAP) was used as a water-soluble UV photoinitiator to form the PulMA/PEGDA hydrogel by photopolymerization strategy. Compared with the pure PulMA hydrogel, the increase of PEGDA concentration led to a slower degradation rate and an increase of residual mass from 63.9% to 86.8%. There was about 8-fold increase in storage modulus (G′) (reach to 16.0 × 103 Pa) and 13-fold increase in compressive modulus (reach to 1.17 ± 0.17 MPa) with increasing the concentration of PEGDA to 15% (w/v) in the hydrogel. In cell culture in vitro, the rabbit’s mesenchymal stem cells (MSCs) encapsulated in the PulMA/PEGDA hydrogel could adhere and proliferate, indicating that the PulMA/PEGDA hydrogel had a good biocompatibility. Furthermore, the hydrogels supported glycosaminoglycan (GAG) synthesis, and chondrogenic phenotype of MSCs with TGF-β3-containing chondrogenic medium. This study demonstrated that the photo-crosslinking PulMA/PEGDA hydrogels, with good mechanical properties and slow degradation rate are promising scaffolds for cartilage repair and regeneration.

High performance n-type thermoelectric material based on naphthalenediimide radical anions

An ideal organic thermoelectric (TE) material should possess features that would be low-cost, of high performance, easy to process, and non-toxic, but it is rare to find materials that meet these requirements. Naphthalenediimide (NDI), as a common and cheap industrial pigment, displays strong intermolecular inaction and good n-type semiconductor character. However, due to the strong interaction of π-π and hydrogen bond interaction, NDI usually exhibited poor solubility, making it difficult to process in solution. Herein, we demonstrated that the unsubstituted NDI could form a suspension mixed with NDI radical anion state by phenyl lithium doping, which consequently can be used to prepare dense film by drop-casting for TE application. More importantly, by optimizing the doping ratio, the TE film reached electrical conductivity of 0.11 S cm−1 and Seebeck coefficient of −1289 μV K−1. Eventually, a high power factor up to 18.8 μW m−1 K−2 and ZT value of 0.053 was obtained, which is one of the best TE performance achieved in n-type NDI-based TE materials. This work suggests the simple strategy of utilizing commercially mature molecules to develop organic TE materials with high performance.

A Tough Polysaccharide-Based Hydrogel with an On-Demand Dissolution Feature for Chronic Wound Care through Light-Induced Ultrafast Degradation.

Repeatedly changing dressings during wound healing can cause unbearable physical pain for patients with chronic skin injury. In this study, we designed a tough hydrogel-based dressing that can be degraded in an on-demand fashion for advanced chronic wound care. The resultant hydrogel dressing could be rapidly dissolved within 100 s after wetting with lithium phenyl(2,4,6-trimethylbenzonyl)phosphinate solution under low-power (1 W) ultraviolet (UV) irradiation (365 nm) owing to the breakage of disulfide bonds. This UV-triggered on-demand dissolution of tough hydrogels allows for a facile dressing replacement without causing tissue damage or pain, which is of great potential for clinical utilization.

Photopolymerization-Based Synthesis of Uniform Magnetic Hydrogels and Colorimetric Glucose Detection.

Magnetic hydrogels have been commonly used in biomedical applications. As magnetite nanoparticles (MNPs) exhibit peroxidase enzyme-like activity, magnetic hydrogels have been actively used as signal transducers for biomedical assays. Droplet microfluidics, which uses photoinitiated polymerization, is a preferred method for the synthesis of magnetic hydrogels. However, light absorption by MNPs makes it difficult to obtain fully polymerized and homogeneous magnetic hydrogels through photoinitiated polymerization. Several methods have been reported to address this issue, but few studies have focused on investigating the light absorption properties of photoinitiators. In this study, we developed a simple method for the synthesis of poly(ethylene glycol) (PEG)-based uniform magnetic hydrogels that exploits the high ultraviolet absorption of a photoinitiator. Additionally, we investigated this effect on shape deformation and structural uniformity of the synthesized magnetic hydrogels. Two different photoinitiators, Darocur 1173 and lithium phenyl (2,4,6–trimethylbenzoyl) phosphinate (LAP), with significantly different UV absorption properties were evaluated based on the synthesis of magnetic hydrogels. The magnetic characteristics of the PEG-stabilized MNPs in hydrogels were investigated with a vibrating sample magnetometer. Finally, the colorimetric detection of hydrogen peroxide and glucose was conducted based on the enzyme-like property of MNPs and repeated several times to observe the catalytic activity of the magnetic hydrogels.

The Photoinitiator Lithium Phenyl (2,4,6-Trimethylbenzoyl) Phosphinate with Exposure to 405 nm Light Is Cytotoxic to Mammalian Cells but Not Mutagenic in Bacterial Reverse Mutation Assays.

Lithium phenyl (2,4,6-trimethylbenzoyl) phosphinate (LAP) is a free radical photo-initiator used to initiate free radical chain polymerization upon light exposure, and is combined with gelatin methacryloyl (GelMA) to produce a photopolymer used in bioprinting. The free radicals produced under bioprinting conditions are potentially cytotoxic and mutagenic. Since these photo-generated free radicals are highly-reactive but short-lived, toxicity assessments should be conducted with light exposure. In this study, photorheology determined that 10 min exposure to 9.6 mW/cm2 405 nm light from an LED light source fully crosslinked 10 wt % GelMA with >3.4 mmol/L LAP, conditions that were used for subsequent cytotoxicity and mutagenicity assessments. These conditions were cytotoxic to M-1 mouse kidney collecting duct cells, a cell type susceptible to lithium toxicity. Exposure to ≤17 mmol/L (0.5 wt %) LAP without light was not cytotoxic; however, concurrent exposure to ≥3.4 mmol/L LAP and light was cytotoxic. No condition of LAP and/or light exposure evaluated was mutagenic in bacterial reverse mutation assays using S. typhimurium strains TA98, TA100 and E. coli WP2 uvrA. These data indicate that the combination of LAP and free radicals generated from photo-excited LAP is cytotoxic, but mutagenicity was not observed in bacteria under typical bioprinting conditions.

Visible Light Cross-Linking of Gelatin Hydrogels Offers an Enhanced Cell Microenvironment with Improved Light Penetration Depth.

In this study, the cyto-compatibility and cellular functionality of cell-laden gelatin-methacryloyl (Gel-MA) hydrogels fabricated using a set of photo-initiators which absorb in 400-450 nm of the visible light range are investigated. Gel-MA hydrogels cross-linked using ruthenium (Ru) and sodium persulfate (SPS), are characterized to have comparable physico-mechanical properties as Gel-MA gels photo-polymerized using more conventionally adopted photo-initiators, such as 1-[4-(2-hydroxyethoxy)-phenyl]-2-hydroxy-2-methyl-1-propan-1-one (Irgacure 2959) and lithium phenyl(2,4,6-trimethylbenzoyl) phosphinate (LAP). It is demonstrated that the Ru/SPS system has a less adverse effect on the viability and metabolic activity of human articular chondrocytes encapsulated in Gel-MA hydrogels for up to 35 days. Furthermore, cell-laden constructs cross-linked using the Ru/SPS system have significantly higher glycosaminoglycan content and re-differentiation capacity as compared to cells encapsulated using I2959 and LAP. Moreover, the Ru/SPS system offers significantly greater light penetration depth as compared to the I2959 system, allowing thick (10 mm) Gel-MA hydrogels to be fabricated with homogenous cross-linking density throughout the construct. These results demonstrate the considerable advantages of the Ru/SPS system over traditional UV polymerizing systems in terms of clinical relevance and practicability for applications such as cell encapsulation, biofabrication, and in situ cross-linking of injectable hydrogels.

Photopolymerizable biogel scaffold seeded with mesenchymal stem cells: safety and efficacy evaluation of novel treatment for intervertebral disc degeneration.

Tissue engineering approaches to treatment of intervertebral disc degeneration (IDD) represent a novel avenue of addressing the biologic basis of this disease. However, such approaches remain limited by their invasive nature and disruption to the annular fibrosis (AF). This study sought to explore a new minimally-invasive tissue-engineering approach utilizing an injection of a photopolymerizable biogel scaffold seeded with mesenchymal stem cells (MSCs) directly into the nucleus pulposus (NP). This study was performed using rabbit specimens for both in vivo and in vitro outcome measures. The treatment in this study was performed by injecting 25 μl of 10% (w/v) methacrylated gelatin biogel with 0.15% (w/v) lithium phenyl 2,4,6-trimethylbenzoylphosphinate (LAP) and rabbit MSCs (1 × 106 ) cells/ml into the NP. Samples were then photopolymerized in situ using non-ultraviolet light irradiation via a fiberoptic wire. For the in vitro arm of this study, gene expression analysis demonstrated increased anabolic activity in irradiated MSCs with and without biogel scaffolds. For the in vivo arm of this study, while GAG analysis did not demonstrate significant differences between groups, MRI analysis exhibited a trend toward improved NP matrix. Histological analysis was consistent with increased cellularity and less severe disc degeneration in the MSC + Gel group. However, osteophyte formation was noted in both Stab and MSC + Gel groups after the study period. Increased matrix gene expression of irradiated groups within in vitro studies indicates a photobiologic effect of 405 nm light. Despite promising anabolic actions, osteophyte formation and AF defects could not be avoided with implementation of this minimally-invasive tissue-engineering approach. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1451-1459, 2019.

Grignard Reagents and Their N‐analogues in the Synthesis of Tricyclic and Tetracyclic Cage‐like Lactams

A convenient method is reported for the synthesis of 34 novel tricyclic and tetracyclic cage‐like lactams in high to excellent yields. The method involves treatment of easily available exo‐2,3‐epoxy(or Ts‐aziridino)bicyclo[2.2.1]heptan‐endo‐5,6‐dicarboximides by Grignard reagents, their N‐analogues, or phenyl lithium in tetrahydrofuran. In silico screening of biological activity spectrum showed high probability levels of glyceryl‐ether monooxygenase inhibitory, testosterone 17β‐dehydrogenase (NADP+) inhibitory, bilirubin oxidase inhibitory, and anti‐ischemic activity for tetracyclic derivatives.

A snapshot of inorganic Janovsky complex analogues featuring a nucleophilic boron center.

The addition of phenyl lithium (PhLi) to an aromatic 1,3,2,5-diazadiborinine (1) afforded isolable ionic species 2, which can be deemed as an inorganic analogue of a Janovsky complex. X-ray diffraction analysis and DFT studies of 2 indicate the delocalization of π-type electrons mainly over the C-B-C unit in the central B2C2N2 six-membered ring. The reactions of 2 with methyl iodide (MeI) and chloro(tricyclohexylphosphine)gold(i) (Cy3PAuCl) gave 3 bearing a B-Me bond and 4 featuring a B-Au bond, respectively, demonstrating the nucleophilic properties of the tricoordinate boron center in 2.