Bioactive Phenolate Salts: Thymol Salts.

Phenolate salts of bioactive agents have been reported only scarcely. This is the first report on the formation and characterization of thymol phenolate salts as representatives of phenol-containing bioactive molecules. Thymol has been used in medicine and agriculture for decades owing to its excellent therapeutic properties. However, in light of its poor aqueous solubility, thermal instability, and especially its high chemical volatility, the utility of thymol is hampered. The present work focuses on tuning the physicochemical properties of thymol by modifying its chemical structure through salt formation. In this context, a series of metal (Na, K, Li, Cu, and Zn) and ammonium (tetrabutylammonium and choline) salts of thymol were synthesized and characterized using IR, NMR, CHN elemental analysis, and DSC analyses. The molecular formulae of thymol salts were determined based on CHN analysis and thymol quantification studies from UV-Vis spectrometric analysis. In most cases, the thymol phenolate was prepared as a 1 : 1 molar ratio with metal/ammonium ion. Only the Cu salt of thymol was isolated at a ratio of two phenolate units per copper ion. Most of the synthesized thymol salts were found to have increased thermal stability relative to thymol. The physicochemical properties such as solubility, thermal stability, and evaporation rate of thymol salts were thoroughly studied in comparison with thymol. The in vitro release studies of Cu from the copper salt of thymol is pH-dependent: rapid release of copper was observed in the lower pH release medium (100 % release at pH 1 for 12 days) and the rates of release were slower at higher pH values (5 % release at pH 2, and <1 % release at pH 4, 6, 8, and 10) over a period of about three weeks.

Polyanhydride Chemistry.

Polyanhydrides (PAs) are a class of synthetic biodegradable polymers employed as controlled drug delivery vehicles. They can be synthesized and scaled up from low-cost starting materials. The structure of PAs can be manipulated synthetically to meet desirable characteristics. PAs are biocompatible, biodegradable, and generate nontoxic metabolites upon degradation, which are easily eliminated from the body. The rate of water penetrating into the polyanhydride (PA) matrix is slower than the anhydride bond cleavage. This phenomenon sets PAs as "surface-eroding drug delivery carriers." Consequently, a variety of PA-based drug delivery carriers in the form of solid implants, pasty injectable formulations, microspheres, nanoparticles, etc. have been developed for the sustained release of small molecule drugs, and vaccines, peptide drugs, and nucleic acid-based active agents. The rate of drug delivery is often controlled by the polymer erosion rate, which is influenced by the polymer structure and composition, crystallinity, hydrophobicity, pH of the release medium, device size, configuration, etc. Owing to the above-mentioned interesting physicochemical and mechanical properties of PAs, the present review focuses on the advancements made in the domain of synthetic biodegradable biomedical PAs for therapeutic delivery applications. Various classes of PAs, their structures, their unique characteristics, their physicochemical and mechanical properties, and factors influencing surface erosion are discussed in detail. The review also summarizes various methods involved in the synthesis of PAs and their utility in the biomedical domain as drug, vaccine, and peptide delivery carriers in different formulations are reviewed.

Lignin: Drug/Gene Delivery and Tissue Engineering Applications.

Lignin is an abundant renewable natural biopolymer. Moreover, a significant development in lignin pretreatment and processing technologies has opened a new window to explore lignin and lignin-based bionanomaterials. In the last decade, lignin has been widely explored in different applications such as drug and gene delivery, tissue engineering, food science, water purification, biofuels, environmental, pharmaceuticals, nutraceutical, catalysis, and other interesting low-value-added energy applications. The complex nature and antioxidant, antimicrobial, and biocompatibility of lignin attracted its use in various biomedical applications because of ease of functionalization, availability of diverse functional sites, tunable physicochemical and mechanical properties. In addition to it, its diverse properties such as reactivity towards oxygen radical, metal chelation, renewable nature, biodegradability, favorable interaction with cells, nature to mimic the extracellular environment, and ease of nanoparticles preparation make it a very interesting material for biomedical use. Tremendous progress has been made in drug delivery and tissue engineering in recent years. However, still, it remains challenging to identify an ideal and compatible nanomaterial for biomedical applications. In this review, recent progress of lignin towards biomedical applications especially in drug delivery and in tissue engineering along with challenges, future possibilities have been comprehensively reviewed.

Solid-State Isolation of Cyclic Alkyl(Amino) Carbene (cAAC)-Supported Structurally Diverse Alkali Metal-Phosphinidenides.

Cyclic alkyl(amino) carbene (cAAC)-supported, structurally diverse alkali metal-phosphinidenides 2-5 of general formula ((cAAC)P-M)n (THF)x [2: M=K, n=2, x=4; 3: M=K, n=6, x=2; 4: M=K, n=4, x=4; 5: M=Na, n=3, x=1] have been synthesized by the reduction of cAAC-stabilized chloro-phosphinidene cAAC=P-Cl (1) utilizing metallic K or KC8 and Na-naphthalenide as reducing agents. Complexes 2-5 have been structurally characterized in solid state by NMR studies and single crystal X-ray diffraction. The proposed mechanism for the electron transfer process has been well-supported by cyclic voltammetry (CV) studies and Density Functional Theory (DFT) calculations. The solid state oligomerization process has been observed to be largely dependent on the ionic radii of alkali metal ions, steric bulk of cAAC ligands and solvation/de-solvation/recombination of the dimeric unit [(cAAC)P-M(THF)x ]2 .

Highly fluorescent aryl-cyclopentadienyl ligands and their tetra-nuclear mixed metallic potassium-dysprosium clusters.

Two alkyl substituted triaryl-cyclopentadienyl ligands [4,4'-(4-phenylcyclopenta-1,3-diene-1,2-diyl)bis(methylbenzene) (1) and 4,4',4''-(cyclopenta-1,3-diene-1,2,4-triyl)tris(methylbenzene) (2)] have been synthesized via cross-aldol condensation followed by Zn-dust mediated cyclization and acid catalyzed dehydration reactions. The fluorescence properties of 1 and 2 have been studied in solution and solid state. The ligands exhibited aggregation-induced emission enhancement (AIEE) in THF/water solution. 1 and 2 have been found to be significantly more fluorescent in the solid state than in their respective solutions. This phenomenon can be attributed to the strong intermolecular CH⋯π interactions present in 1 and 2 which leads to the tight packing of molecules in their solid-state. Both 1, 2 and their corresponding anions have been studied by theoretical calculations. Ligands 1 and 2 have been shown to react with anhydrous DyCl3 in the presence of potassium metal at high temperature to afford two fluorescent chloride-bridged tetra-nuclear mixed potassium-dysprosium metallocenes [(Me2Cp)4Dy2 IIICl4K2]·3.5(C7H8) (5) and [(Me3Cp)4Dy2 IIICl4K2]·3(C7H8) (6), respectively in good yields.

EUV photofragmentation study of hybrid nonchemically amplified resists containing antimony as an absorption enhancer.

A detailed investigation to understand the mechanism of the resist action at a fundamental level is essential for future Extreme Ultraviolet Lithography (EUVL) resists. The photodynamics study of a newly developed hybrid nonchemically amplified 2.15%-MAPDSA-MAPDST resist using synchrotron radiation excitation at 103.5 eV (12 nm) is presented. Antimony was incorporated in the resist as a heavy metal absorption center in the form of antimonate (2.15%). The results showed the fast decomposition rate of the radiation sensitive sulfonium triflate. HR-XPS and sulfur L-NEXAFS spectra of the copolymer films revealed that after irradiation the Ar-S+-(CH3)2 sulfonium group bonded to the phenyl ring resisted the EUV excitation. Those results confirmed the polarity switching mechanism from hydrophilic sulfonium triflates to hydrophobic aromatic sulfides obtained in previous results. The inorganic component SbF6 - included in the resist formulations as an EUV absorption enhancer was particularly illustrative of the photofragmentation process. F 1s and O 1s HR-XPS spectra showed that fluorine remains linked to the antimony, even after 15 min of irradiation. A change of the antimony oxidation state was also observed with an increase in irradiation time. The presence of the heavy metal may control the high energy deposited on the resist which finally led to very well resolved 20 nm isolated line patterns by EUVL. The 10 times improved sensitivity compared with previous poly-MAPDST resists studied in the past showed the potential of this class of hybrid resists for next generation semiconductor industry applications.

Correction: EUV photofragmentation study of hybrid nonchemically amplified resists containing antimony as an absorption enhancer.

[This corrects the article DOI: 10.1039/C7RA12934C.].

Polyarylenesulfonium Salt as a Novel and Versatile Nonchemically Amplified Negative Tone Photoresist for High-Resolution Extreme Ultraviolet Lithography Applications.

The present report demonstrates the potential of a polyarylenesulfonium polymer, poly[methyl(4-(phenylthio)-phenyl)sulfoniumtrifluoromethanesulfonate] (PAS), as a versatile nonchemically amplified negative tone photoresist for next-generation lithography (NGL) applications starting from i-line (λ ∼ 365 nm) to extreme ultraviolet (EUV, λ ∼ 13.5 nm) lithography. PAS exhibited considerable contrast (γ), 0.08, toward EUV and patterned 20 nm features successfully.