The Cambridge Structural Database in Retrospect and Prospect

The Cambridge Crystallographic Data Centre (CCDC) was established in 1965 to record numerical, chemical and bibliographic data relating to published organic and metal–organic crystal structures. The Cambridge Structural Database (CSD) now stores data for nearly 700 000 structures and is a comprehensive and fully retrospective historical archive of small‐molecule crystallography. Nearly 40 000 new structures are added each year. As X‐ray crystallography celebrates its centenary as a subject, and the CCDC approaches its own 50th year, this article traces the origins of the CCDC as a publicly funded organization and its onward development into a self‐financing charitable institution. Principally, however, we describe the growth of the CSD and its extensive associated software system, and summarize its impact and value as a basis for research in structural chemistry, materials science and the life sciences, including drug discovery and drug development. Finally, the article considers the CCDC’s funding model in relation to open access and open data paradigms.     

Flow Injection Chemiluminescence Method for Nalbuphine Hydrochloride in Pharmaceutical Formulations Using Tris(2,2'-bipyridyl)ruthenium(II) Chloride-diperiodatocuprate(III) Reaction

Asensitive and selective method employing chemiluminescence(CL) coupled with flow injection(FI) is reported for nalbuphine hydrochloride(NAL) assay in pharmaceutical formulations. The enhancement effect of NAL on the CL reaction between tris(2,2'-bipyridyl)ruthenium(II) chloride-diperiodatocuprate(III) {Ru[(bpy)₃]²⁺-Cu(III) complex} in acidic medium is used as analytical measurement. The optimal conditions of the CL reaction were sulfuric acid 1.0×10^-3 mol/L, Ru[(bpy)₃]²⁺ 7.5×10^-5 mol/L, Cu(III)/Ag(III) complexes 4.0×10^-4/5.0×10^-4 mol/L, sample loop volume of 120 μL and flow rate of 2.5 mL/min. The sensitivities of the method in terms of detection(S/N=3) and quantification(S/N=10) limits are 5×10^-4 and 0.001 ppm(1 ppm=1 mg/L), respectively. The linear response of the instrument in the form of CL intensity with respect to NAL concentration is over the range 0.001-15.0 ppm(R²=0.9999) with relative standard deviation from 0.8% to 3.2% and injection throughput of 120 injection/h. The applications of the method include the quantitative analysis of NAL in pharmaceutical injection samples. Variations and the average results of the proposed method are not signi-ficantly different from the results of a reported method by applying F- and paired student t-test. The most likely CL reaction mechanism is written in accordance with spectrophotometric and CL studies.     

Increasing Complexity: A Practical Synthetic Approach to Three-Dimensional,Cyclic Sulfoximines and First Insights into Their in Vitro Properties

A short synthetic approach with broad scope to access five- to seven-membered cyclic sulfoximines in only two to three steps from readily available thiophenols is reported. Thus, simple building blocks were converted to complex molecular structures by a sequence of S-alkylation and one-pot sulfoximine formation, followed by intramolecular cyclization. Seventeen structurally diverse cyclic sulfoximines were prepared in high overall yields. In vitro evaluation of these underrepresented, three-dimensional, cyclic sulfoximines with respect to properties relevant to medicinal chemistry did not reveal any intrinsic flaw for application in drug discovery.     

The Role of Fluorine in Glycomimetic Drug Design

Glycans are well established to play important roles at various stages of infection and disease, and ways to modulate these interactions have been sought as novel therapies. The use of native glycan structures has met with limited success, which can be attributed to their characteristic high polarity (e.g., low binding affinities) and inherently poor pharmacokinetic properties (e.g., short drug–target residence times, rapid renal excretion), leading to the development of ′glycomimetics′. Fluorinated drugs have become increasingly common over recent decades, with fluorinated glycomimetics offering some unique advantages. Deoxyfluorination maintains certain electrostatic interactions, while concomitantly reducing net polarity through ′polar hydrophobicity′, improving residence times and binding affinities. Fluorination destabilizes the oxocarbenium transition state associated with metabolic degradation, and can restore exo- and endo-anomeric effects in C-glycosides and carbasugars. Lastly, it has shown great utility in radiotracer development and enhancement of antigenicity in glycan-based vaccines. Owing to synthetic challenges, fluorinated glycomimetics have been somewhat underutilized to date, but methodological improvements will advance their use in glycomimetic drugs.     

Voltammetric Study and Direct Analytical Determination of the Antiparkinson Drug Benserazide

For the first time, a simple differential pulse voltammetry methodology for direct determination of benserazide in presence of levodopa in tablets was developed without any redox mediator, modified electrodes, or the aplication of mathematic deconvolution of signals. Benserazide was studied by differential pulse voltammetry using glassy carbon electrode in aqueous media. The drug exhibited a main well-defined oxidation signal in a broad pH range (2–10), and two poorly resolved signals at higher potentials. We have found that levodopa does not interfere on the electrochemical response of benserazide at pH 6.0. Thus, at this pH value, the developed analytical method exhibited adequate repeatability and reproducibility (RSD < 2%), recoveries >98.5%, which permitted its successful application to both the assay and the uniformity content of benserazide. Also, hydrolytic degradation studies of benserazide were carried out by differential pulse voltammetry.     

Engyodontochones,Antibiotic Polyketides from the Marine Fungus Engyodontium album Strain LF069

Six new ( 2 , 4 – 8 ) and two known polyketides with a basic structure of an anthraquinone‐xanthone were isolated from mycelia and culture broth of the fungus Engyodontium album strain LF069. The structures and relative configurations of these compounds were established by spectroscopic means, and their absolute configurations were defined mainly by comparison of quantum chemical TDDFT calculated and experimental ECD spectra. Compounds 2 and 4 – 8 were given the trivial names engyodontochone A ( 2 ) and B–F ( 4 – 8 ). Compounds 5 – 8 represent the first example of a 23,28 seco‐beticolin carbon skeleton. The relative and absolute configurations of two known substances JBIR‐97/98 ( 1 ) and JBIR‐99 ( 3 ) were determined for the first time. All isolated compounds were subjected to bioactivity assays. Compounds 1 – 4 exhibited inhibitory activity against methicillin‐resistant Staphylococcus aureus (MRSA) that was 10‐fold stronger than chloramphenicol.     

Spectrophotometric Determination Of Rifampin in the Presence of its Degradation Products in Pharmaceutical Preparations

Abstract

The determination of rifampin in the presence of its main degradation products, 3-formyl rifampin and rifampin quinone using two spectrophotometric methods is described. Both Glenn's method and first derivative spectrophotometry were successfully adopted. No preliminary separation steps were required in either cases. Both methods gave accurate and reproducible results for the determination of the drug in dosage forms. The percentage recoveries ranged from 99.33% ±0.63 to 100.2% ± 0.44. The proposed methods are more simple, rapid than other existing methods and can be readily adopted in control laboratory.