1H NMR spectroscopic investigation of β-cyclodextrin inclusion compounds with parecoxib

The inclusion complexes of β-CD and parecoxib [PRB] in aqueous solution were investigated using ¹H NMR spectroscopic study revealed the existence of four different equilibria for 1:1 inclusion complexes in which both the aromatic rings of the guest are tightly held by the host cavity. The NMR spectra of the PRB studied in the presence of β-CD are fully assigned and interpreted by means of COSY spectrum for the unambiguous assignment of guest aromatic ring protons. The parallel interpretation of β-CD chemical shift changes and dipolar contacts, with the aid of 2D ROESY, allows the mode of binding to be established for four possible structures of 1:1 PRB-β-CD inclusion complexes.     

Quantitative TLC of Toxic Elements on Inorganic Ion-exchangers. VI. Separation and Determination of Cadmium

JPC – Journal of Planar Chromatography – Modern TLC -     

Biotinylation of Peptides/Proteins Using Biocytin Hydrazide

Biocytin hydrazide is widely used to biotinylate the carbohydrate moieties of glycoproteins. In this study, however, biocytin hydrazide was found to be able to directly biotinylate peptides and proteins. This phenomenon may cause false identification of non‐glycopeptides/non‐glycoproteins as glycopeptides/glycoproteins. Here, we report a systematic investigation of the reaction of peptides/proteins with biocytin hydrazide. Matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry is used to analyze the biotinylation reaction between peptides/proteins and biocytin hydrazide. Peptides/proteins were reacted with biocytin hydrazide in diverse solvent systems with different biocytin hydrazide concentrations for up to 96 h at temperatures ranging from 4 °C to 65 °C. Singly biotinylated or multiply biotinylated peptides/proteins are observed. The efficiency of the biotinylation reaction increases with higher temperature, higher biocytin hydrazide concentration, or longer reaction time. The influence of buffer pH on the biotinylation reaction of peptides/proteins is less pronounced. The biotinylation efficiency is optimum at neutral pH. Data suggests that the peptides are biotinylated as efficiently as proteins. The observation that peptides/proteins condense only with biocytin hydrazide, 2‐iminobiotin hydrazide, adipic dihydrazide and phenyl hydrazine but not with biocytin HCl and 2‐iminobiotin, indicates that the biotinylation reaction of peptides/proteins occurs with the hydrazide moiety but not with biotin moiety of the biotinylated reagent. The postsource decay data of biotinylated P₁₄R indicates that biocytin hydrazide condenses with the guanidino group of arginine's side chain of P₁₄R, indicating that besides N‐terminal and lysine residue of peptides/proteins, arginine residue is capable of reacting with biocytin hydrazide.     

Polymeric alkenoxy amino acid surfactants: I. Highly selective class of molecular micelles for chiral separation of beta-blockers

Two amino acid-based alkenoxy micelle polymers were synthesized for this study. These include polysodium N-undecenoxy carbonyl-L-leucinate (poly-L-SUCL) and polysodium N-undecenoxy carbonyl-L-isoleucinate (poly-L-SUCIL). The polymerization time and concentration of the synthesized micelle polymers were optimized by (1)H-nuclear magnetic resonance (NMR) and capillary electrophoresis (CE) experiments. Detailed physicochemical properties ((1)H NMR, critical micelle concentration (CMC), optical rotation, partial specific volume, aggregation number, and polarity) were determined, and these molecular micelles were introduced as a pseudostationary phase in micellar electrokinetic chromatography to study the molecular recognition and to develop a method for simultaneous separation of eight chiral beta-blockers. It is found that poly-L-SUCL gives overall better chiral resolution and wider chiral window than poly-L-SUCIL. After optimizing the type of micelle polymer, injection size and temperature, simultaneous separation and enantioseparation of eight beta-blockers were achieved in less than 35 min. A comparison with the amide-type surfactants of the same polar head group and alkyl chain length showed that carbamate-type surfactants always work better than the corresponding amide-type surfactant.     

The importance of impurity analysis in pharmaceutical products: an integrated approach

To purify a material and remove the excess impurities one should first recognize that whether they are actually present and what their nature is. In the past, this was not always done. But presently drug analysis and pharmaceutical impurities are the subjects of constant review in the public interest. The International Conference on Harmonisation (ICH) guidelines achieved a great deal in harmonizing the definitions of the impurities in new drug substances. It is necessary to perform all the investigations on appropriate reference standards of drug and impurities to get meaningful specifications. In order to meet the challenges to ensure high degree of purity of drug substances and drug products, a scheme is proposed for profiling drug impurity. Finally, analytical methods based on analytical instrumentation must be employed to quantitate drug substance and its impurities. Important aspects and suggestions related to drug analysis and pharmaceutical impurities are discussed.     

Crystal structure,shape analysis and bioactivity of new LiI,NaI and MgII complexes with 1,10‐phenanthroline and 2‐(3,4‐dichlorophenyl)acetic acid

Reactions of 1,10‐phenanthroline (phen) and 2‐(3,4‐dichlorophenyl)acetic acid (dcaH) with M_n(CO₃) (M = Li^I, Na^I and Mg^II; n = 1 and 2) in MeOH yield the mononuclear lithium complex aqua[2‐(3,4‐dichlorophenyl)acetato‐κO](1,10‐phenanthroline‐κ²N,N′)lithium(I), [Li(C₈H₅Cl₂O₂)(C₁₂H₈N₂)(H₂O)] or [Li(dca)(phen)(H₂O)] ( 1 ), the dinuclear sodium complex di‐μ‐aqua‐bis{[2‐(3,4‐dichlorophenyl)acetato‐κO](1,10‐phenanthroline‐κ²N,N′)sodium(I)}, [Na₂(C₈H₅Cl₂O₂)₂(C₁₂H₈N₂)₂(H₂O)₂] or [Na₂(dca)₂(phen)₂(H₂O)₂] ( 2 ), and the one‐dimensional chain magnesium complex catena‐poly[[[diaqua(1,10‐phenanthroline‐κ²N,N′)magnesium]‐μ‐2‐(3,4‐dichlorophenyl)acetato‐κ²O:O′] 2‐(3,4‐dichlorophenyl)acetate monohydrate], {[Mg(C₈H₅Cl₂O₂)(C₁₂H₈N₂)(H₂O)₂](C₈H₅Cl₂O₂)·H₂O}_n or {[Mg(dca)(phen)(H₂O)₂](dca)·H₂O}_n ( 3 ). In these complexes, phen binds via an N,N′‐chelate pocket, while the deprotonated dca^? ligands coordinate either in a monodentate (in 1 and 2 ) or bidentate (in 3 ) fashion. The remaining coordination sites around the metal ions are occupied by water molecules in all three complexes. Complex 1 crystallizes in the triclinic space group P with one molecule in the asymmetric unit. The Li⁺ ion adopts a four‐coordinated distorted seesaw geometry comprising an [N₂O₂] donor set. Complex 2 crystallizes in the triclinic space group P with half a molecule in the asymmetric unit, in which the Na⁺ ion adopts a five‐coordinated distorted spherical square‐pyramidal geometry, with an [N₂O₃] donor set. Complex 3 crystallizes in the orthorhombic space group P2₁2₁2₁, with one Mg²⁺ ion, one phen ligand, two dca^? ligands and three water molecules in the asymmetric unit. Both dcaH ligands are deprotonated, however, one dca^? anion is not coordinated, whereas the second dca^? anion coordinates in a bidentate fashion bridging two Mg²⁺ ions, resulting in a one‐dimensional chain structure for 3 . The Mg²⁺ ion adopts a distorted octahedral geometry, with an [N₂O₄] donor set. Complexes 1 – 3 were evaluated against urease and α‐glucosidase enzymes for their inhibition potential and were found to be inactive.     

cis-Selective synthesis of 2,5-disubstituted pyrrolidines

A concise approach to cis-2,5-disubstituted pyrrolidines is reported, which relies upon N-tert-butoxycarbonylmethyl substitution in a substrate derived from pyroglutamic acid. The method is especially noteworthy since a significant improvement in the conditions for a key Lawesson’s reaction have been established. Regioselective enolate generation and alkylation permits extension of the C-5 side chain.     

Controlled release of 2‐heptanone using starch gel and polycaprolactone matrices and polymeric films

Varroa jacobsoni is a parasitic mite that is threatening the honeybee industry in many parts of the world. 2‐Heptanone, a natural product made by honeybees at low concentrations, is effective at elevated concentrations in controlling mite populations in honeybee colonies, especially when released over a 42 day period. An extrusion process was used to encapsulate 14, 18, and 25% 2‐heptanone in a polycaprolactone (PCL) matrix. Less than 18% of the 2‐heptanone was encapsulated in the PCL matrix. The high vapor permeability of PCL to 2‐heptanone resulted in a high flux rate and limited the usefulness of PCL as an encapsulation matrix for controlled‐release devices. A starch gel containing three times its weight in 2‐heptanone was prepared from starch‐based microcellular foam (MCF). The gel had compressive, tensile, and flexural strength values in the range of 0.56 to 1.9 MPa. 2‐Heptanone quickly evaporated from non‐laminated gels. However, when the gel was laminated with different polymeric films, a wide range of flux rates was obtained. The T₅₀ for gels laminated or coated with poly(vinyl alcohol) (PVAL, 99% hydrolyzed) and ethylene‐vinyl alcohol copolymer (EVAL) was 72 and 1030 days, respectively. The most promising film was a starch/glycerol film that released 50% of the 2‐heptanone (T₅₀) in approximately 13 days. Copyright © 2007 John Wiley & Sons, Ltd.     

Incorporation of peptide bonds in the synthesis of polyazamacrocyclic complexes

Summary A new series of 15- and 16-membered dioxotetraamine macrocyclic complexes, [ML¹X₂] and [ML²X₂] (M = Mn^II, Co^II, Ni^II, Cu^II or Zn^II; X = Cl or NO₃), respectively, were prepared by reacting o-aminobenzoic acid, diaminoethane or 1,3-diaminopropane with 2,4-pentanedione in the presence of metal ions. The complexes were identified by analytical data, i.r., ¹H-n.m.r., e.p.r. and u.v.-vis. spectroscopies, and by conductivity and magnetic moment measurements. They exhibit an octahedral geometry leaving the peptide oxygen uncoordinated. They are air stable and insoluble in water and most organic solvents, but soluble in DMSO and DMF. The low conductivity suggests that the complexes are non-ionic.     

Structure and biological activity of a new rotenoid from Pongamia pinnata

Pongarotene (1), a new rotenoid and karanjin (2), a known flavonol, were isolated from the seeds of Pongamia pinnata. The structure determination of these compounds were based on spectral analyses including 2D-NMR. The antifungal, antibacterial and phytotoxicity results of pure compounds 1 and 2 as well as of the methanol (M) and ethyl acetate (E) crude extracts are also being reported.