(Press-News.org) YANG Nan, MAO ZongWan and SUN HongZhe et al., at the Department of Chemistry, University of Hong Kong and Sun Yat-sen University have characterized a series of bismuth citrate complexes by X-ray crystallography and modeled the structure of ranitidine bismuth citrate, a medicine used widely for the treatment of peptic ulcer and gastric reflux disease. The polymeric framework of bismuth citrate may serve as a "drug carrier" for delivery of other drugs in the human body. This significant contribution is reported in SCIENCE CHINA Chemistry 2010, 53(10).
Elements that possess anti-bacterial activity have significant medical applications. Bismuth, the heaviest stable element in the periodic table, exhibits anti-bacterial activity against Helicobacter pylori (H. pylori) with minimal toxicity. It is used widely to treat peptic ulcers and gastrointestinal diseases. Ranitidine bismuth citrate (RBC) is a bismuth citrate-based (Bi(cit)-based) drug, developed in 1991. It exhibits efficacy in first-, second- and third-line H. pylori infection therapies when used in combination with other antibiotics, and is more effective than proton pump inhibitor-based (PPI-based) therapy. Because of the importance of Bi(cit)-based drugs, enormous efforts have been made to elucidate their structures. However, there are few structures that reflect the nature of Bi(cit)-based drugs in the stomach.
In this work, the frameworks of four Bi(cit)-based complexes, obtained under acidic conditions to mimic conditions in the stomach, were resolved. A structural model of RBC was proposed based on the crystal structure of one of these frameworks. The decomposition behavior of Bi(cit)-based complexes in aqueous solution was investigated using ESI-MS.
Bi(cit)-based complexes form polymeric porous frameworks with bismuth citrate dimeric units ([Bi(cit)2Bi]2-) forming the skeleton. Since citrate anions in the frameworks are present in the fully deprotonated, tetraanionic form ([C6H4O7]4–), and coordinate with Bi3+ cations, the excess negative charges in these polyanionic frameworks must be balanced by further cations such as K+, [NH4]+, [H3NCH2CH2NH3]2+ or [C5H6N]+. This allows Bi(cit)-based complexes to encapsulate low-molecular mass molecules or ions, either by a diffusion process or via electrostatic interactions, similar to the "uptake process" of cations and small molecules by zeolites. Ranitidine cations were modeled into a simulated structure based on one experimental framework, revealing hydrogen-bond formation between ranitidine molecules and the citrate tetraanions. ESI-MS data indicated that the Bi(cit)-based frameworks degrade from high molecular weight polymers to low molecular weight species in acidic solution.
This paper reports a series of structures of Bi(cit)-based complexes in acidic solution (mimicking the acidic environment of the stomach), establishes an in silico model of a widely used anti-ulcer drug (ranitidine bismuth citrate), and uses experimental ESI-MS data to propose a possible metabolic fate for Bi(cit)-based drugs under the acidic conditions found in the stomach.
INFORMATION:
This work was supported by the Research Grants Council of Hong Kong (HKU 703808P, HKU 704909P, HKU 107C and HKU 75209), the National Natural Science Foundation of China and Livzon Pharmaceutical Ltd.
See the article: Yang N, Mao Z W, Sun H Z et al. Polymeric architectures of bismuth citrate based on dimeric building blocks. Sci China Chem, 2010, 53: 2152-2158, doi: 10.1007/s11426-010-4113-x
DOI: 10.1007/s11434-010-9975-y
Polymeric porous framework of a bismuth citrate-based complex: A potential vehicle for drug delivery
2010-12-04
ELSE PRESS RELEASES FROM THIS DATE:
Faulty gene linked to disorders of sexual development
2010-12-04
Scientists have discovered that the alteration of a single gene could cause some male embryos to develop as females.
The breakthrough will improve diagnosis and clinical management of patients with disorders of sex development (DSD). These conditions occur when the testis or ovary does not develop properly in the embryo, causing genital abnormalities in one in 4500 babies.
An international team including researchers from the Murdoch Childrens Research Institute and the University of Melbourne identified the gene alteration in a group of patients including two families ...
Your Web surfing history is accessible (without your permission) via JavaScript
2010-12-04
The Web surfing history saved in your Web browser can be accessed without your permission. JavaScript code deployed by real websites and online advertising providers use browser vulnerabilities to determine which sites you have and have not visited, according to new research from computer scientists at the University of California, San Diego.
The researchers documented JavaScript code secretly collecting browsing histories of Web users through "history sniffing" and sending that information across the network. While history sniffing and its potential implications for ...
Graptolite fauna indicates the beginning of the Kwangsian Orogeny
2010-12-04
Our research at the State Key Laboratory of Palaeobiology and Stratigraphy, Nanjing Institute of Geology and Palaeontology, has shown, based on a refined division and correlation of the graptolite-bearing strata in southern Jiangxi, China, that the Kwangsian Orogeny commenced in the early Katian Age of the Late Ordovician. Because of its significant research value, this study is published in Issue 11 of Science China Earth Sciences.
An angular unconformity separating the Lower-Middle Devonian and underlying strata is widespread in the Zhujiang region of South China, and ...
India launch of food security report focuses on rice
2010-12-04
Mumbai, India – The International Rice Research Institute (IRRI) and the Asia Society launched a new food security report for Asia in Mumbai today, calling for increased investment in rice research.
The report, Never an empty bowl: sustaining food security in Asia, emphasizes the importance of rice as the primary staple food in Asia and a major source of income for Asian farmers. Existing global efforts to combat hunger and achieve food security are evaluated in the report, which also recommends more research on: climate change mitigation for farming, farming infrastructure, ...
Smashing fluids: The physics of flow
2010-12-04
VIDEO:
Hit it hard and it will fracture like a solid, but tilt it slowly and it will flow like a fluid. This is the intriguing property of a type of...
Click here for more information.
The new findings will be highly useful to the manufacturing industry because the processing and dispensing of everyday products like toothpaste, cosmetics, pharmaceuticals and foodstuffs depends on an understanding of the physical properties and behaviours of these fluids.
The research ...
What can ice reveal about fire?
2010-12-04
Scientists studying a column of Antarctic ice spanning 650 years have found evidence for fluctuations in biomass burning--the consumption of wood, peat and other materials in wildfires, cooking fires and communal fires--in the Southern Hemisphere.
The record, focused primarily on carbon monoxide (CO), differs substantially from the record in the Northern Hemisphere, suggesting changes may be necessary for several leading climate models.
The research appears in Science on Dec. 2, 2010, in an early online release.
The scientists studied variations in stable (non-radioactive, ...
New report summarizes key themes in American doctoral education
2010-12-04
A new report recently released by the National Science Foundation, titled "Doctorate Recipients from U.S. Universities: 2009," presents a statistical overview of the U.S. doctoral education system in snapshots and long-term trends.
It notes the American system of doctoral education is widely considered the world's best, as evidenced by the large number of international students who choose to pursue a doctorate at U.S. universities. But this status is subject to the many factors that shape U.S. doctoral education.
"Given the increased global engagement and economic prosperity ...
Researchers create high performance infrared camera based on type-II InAs/GaSb superlattices
2010-12-04
Researchers at Northwestern University have created a new infrared camera based on Type-II InAs/GaSb superlattices that produces much higher resolution images than previous infrared cameras.
Created by Manijeh Razeghi, Walter P. Murphy Professor of Electrical Engineering and Computer Science, and researchers in the Center for Quantum Devices in the McCormick School of Engineering and Applied Science, the long wavelength infrared focal plane array camera provides a 16-fold increase in the number of pixels in the image and can provide infrared images in the dark. Their ...
Researchers create new high-performance fiber
2010-12-04
Researchers at Northwestern University have nanoengineered a new kind of fiber that could be tougher than Kevlar.
Working in a multidisciplinary team that includes groups from other universities and the MER Corporation, Horacio Espinosa, James N. and Nancy J. Farley Professor in Manufacturing & Entrepreneurship at the McCormick School of Engineering and Applied Science, and his group have created a high performance fiber from carbon nanotubes and a polymer that is remarkably tough, strong, and resistant to failure. Using state-of-the-art in-situ electron microscopy testing ...
The gene-environment enigma
2010-12-04
Personalized medicine centers on being able to predict the risk of disease or response to a drug based on a person's genetic makeup. But a study by scientists at Washington University School of Medicine in St. Louis suggests that, for most common diseases, genes alone only tell part of the story.
That's because the environment interacts with DNA in ways that are difficult to predict, even in simple organisms like single-celled yeast, their research shows.
"The effects of a person's genes – and, therefore, their risk of disease – are greatly influenced by their environment," ...