A Validated Chiral LC Method for the Enantiomeric Separation of Cinacalcet Hydrochloride

A rapid isocratic chiral LC method has been developed for the separation of (S)-cinacalcet from (R)-cinacalcet. Good resolution with R _S  > 3 was obtained using a Chiralpak-IA column (250 × 4.6 mm, particle size 5 μm) and n-hexane, ethanol and trifluoroacetic acid as the mobile phase (95:5:0.1, v/v) at ambient temperature. Flow rate was kept at 1.0 mL min^–1 and elution was monitored by UV detection at 223 nm. This method was further used to determine the presence of (S)-cinacalcet in enantiopure pharmaceutical formulations containing (R)-cinacalcet. This method allowed for the detection and quantitation of (S)-cinacalcet of levels at 0.04 and 0.16 μg mL^–1, respectively. The method was validated following ICH guidelines.     

Regioselective ring-opening of aziridines with potassium thiocyanate and thiols using sulfated zirconia as a heterogeneous recyclable catalyst

Ring-opening of aziridines with potassium thiocyanate and thiols has efficiently been carried out at room temperature in the presence of sulfated zirconia to give the corresponding β-aminothiocyanates and β-aminosulfides, respectively, in high yields within 2 h and with high regioselectivity. The catalyst, a solid acid, functions under heterogeneous conditions.     

One-pot synthesis and biological evaluation of novel 4-[3-fluoro-4-(morpholin-4-yl)]phenyl-1H-1,2,3-triazole derivatives as potent antibacterial and anticancer agents

In search of better antibacterial and anticancer agents, a series of novel 4-[3-fluoro-4-(morpholin-4-yl)]phenyl-1H-1,2,3-triazole derivatives were synthesized ( 6a - l and 8a - j ) by using 3-fluoro-4-morpholinoaniline, alkyne, and triflyl azide via an in situ generated 4-(4-azido-2-fluorophenyl)morpholine and evaluated for their antibacterial and anticancer activity in vitro. Antibacterial activity against three G+ bacterial strains and anticancer activity against breast cancer cell line (MCF-7) and cervical carcinoma cell line (HeLa) was evaluated. Among all the tested compounds, 6h , 6i , and 8b exhibited potent antibacterial activity against tested gram-positive bacterial strains. The anticancer activity screening results of 8f , 8h , and 8i exhibited potent cytotoxic activity against two cancer cell lines with IC₅₀ values nearer to the standard drug, doxorubicin. The remaining compounds have shown good to moderate activity against the tested cell lines. On the basis of the results obtained, a structure-activity relationship (SAR) is discussed.     

Determination of polyethylene glycol end group functionalities by combination of selective reactions and characterization by matrix assisted laser desorption/ionization time-of-flight mass spectrometry

End groups play a critical role in macromolecular coupling reactions for building complex polymer architectures, yet their identity and purity can be difficult to ascertain using traditional analytical technique. Recent advances in mass spectrometry techniques have made matrix-assisted laser desorption/ionization time-of-fight (MALDI-TOF) mass spectrometry a rapid and powerful tool for providing detailed information about the identity and purity of homopolymer end groups. In this work, MALDI-TOF mass spectrometry was used to study end groups of linear polyethylene glycols. In particular, the identifications of alcohol, amine and thiol end groups are investigated because these nucleophilic moieties are among the most common within biological and synthetic macromolecules. Through comparative characterization of alcohol, amine, and thiol end groups, the exact identification of these end groups could be confirmed by selective and quantitative modification. The precision of this technique enables the unambiguous differentiation of primary amino groups relative to hydroxyl groups, which differ by only 1 mass unit. In addition, the quantitative conversion of various polyethylene glycol end groups using highly efficient coupling reactions such as the thiol-ene and azide-alkyne click reactions can be confirmed using MALDI-TOF mass spectrometry.     

Heterocyclizations via POCl3-Based Multicomponent Reactions: A New Approach to One-Pot Synthesis of a New Spirosystem, 7-Methyl-5-[4-(aryl/heteryl)thiazol-2-yl]-5,6-diazaspiro[2,4]hept-6-en-4-ones

A novel multicomponent reaction involving phenacylbromide, thiosemicarbazide, and α-acetyl-γ-butyrolactone in the presence of POCl₃, forming 7-methyl-5-[4-(aryl/heteryl)thiazole-2-yl]-5,8-diaza spiro[2,4]hept-6-en-4-ones in good yields, is described.     

A Short-Lived but Highly Cytotoxic Vanadium(V) Complex as a Potential Drug Lead for Brain Cancer Treatment by Intratumoral Injections

The chemistry and short lifetimes of metal-based anti-cancer drugs can be turned into an advantage for direct injections into tumors, which then allow the use of highly cytotoxic drugs. The release of their less toxic decomposition products into the blood will lead to decreased toxicity and can even have beneficial effects. We present a ternary V^V complex, 1 ([VOL¹L²], where L¹ is N-(salicylideneaminato)-N′-(2-hydroxyethyl)ethane-1,2-diamine and L² is 3,5-di-tert-butylcatechol), which enters cells intact to induce high cytotoxicity in a range of human cancer cells, including T98g (glioma multiforme), while its decomposition products in cell culture medium were ≈8-fold less toxic. 1 was 12-fold more toxic than cisplatin in T98g cells and 6-fold more toxic in T98g cells than in a non-cancer human cell line, HFF-1. Its high toxicity in T98g cells was retained in the presence of physiological concentrations of the two main metal-binding serum proteins, albumin and transferrin. These properties favor further development of 1 for brain cancer treatment by intratumoral injections.     

Pixel size and pitch measurements of liquid crystal spatial light modulator by optical diffraction

We present a simple technique for the determination of pixel size and pitch of liquid crystal (LC) based spatial light modulator (SLM). The proposed method is based on optical diffraction from pixelated LC panel that has been modeled as a two-dimensional array of rectangular apertures. A novel yet simple, two-plane measurement technique is implemented to circumvent the difficulty in absolute distance measurement. Experimental results are presented for electrically addressed twisted nematic LC-SLM removed from the display projector.     

Extraction of fracture mechanics parameters from steady-state dynamic crack-tip fields

A procedure for determining the fracture mechanics parameters of interest from full-field optical mechanics data is presented. Examples are presented for crack-tip stress fields recorded using dynamic photoelasticity. Stress-field representations in series form, when combined with local collocation procedures, are shown to be a powerful tool for reliable and accurate parameter determination. The methodology is illustrated and applied to two cases of dynamic crack propagation, one pertaining to opening-mode crack propagation and the other to a smoothly curving crack. Emphasis has been placed on giving guidance to a user on how best to approach implementation of the methodology from a practical standpoint.