Featured Research

from universities, journals, and other organizations

Century-old Rule Of Chemistry Overturned -- Major Implications For Drug Delivery

Date:
August 25, 2008
Source:
University of Warwick
Summary:
A new study has challenged a century old rule of pharmacology that defined how quickly key chemicals can pass across cell walls. The new observations of the chemists suggest that the real transport rates could be up to a hundred times slower than predicted by the century-old "Overton's Rule." This could have major implications for the development and testing of many future drugs.

A new study by research chemists at the University of Warwick has challenged a century old rule of pharmacology that defined how quickly key chemicals can pass across cell walls.

The new observations of the Warwick researchers suggest that the real transport rates could be up to a hundred times slower than predicted by the century old "Overton's Rule". This could have major implications for the development and testing of many future drugs.

Overton's rule says that the easier it is for a chemical to dissolve in a lipid (fat) the easier and faster it will be transported into a cell. The Rule was first outlined in the 1890s by Ernst Overton of the University of Zόrich. He declared that substances that dissolve in lipids pass more easily into a cell than those that dissolve in water. He then set forth an equation that predicted how fast that diffusion would happen. One of the key parameters in that equation is K which defines the lipophilicity (oil-liking nature) of the chemical. The higher the value of K, the faster the predicted cell permeation rate. For over a century, medicinal chemists have used this relationship to shape their studies and clinical trials.

A team of electrochemists from the University of Warwick used a combination of a confocal microscope and an ultramicroelectrode to study what really happens when a chemical crosses a cell membrane. Advances in technology enabled them to position an ultramicroelectrode incrediblely close to the membrane boundary (roughly 20 microns away; ca. 1/3rd the thickness of a human hair) where it was used to generate a range of acids that should be able to diffuse relatively easily into a cell. These techniques allowed every step of the diffusion process to be directly examined. Previous studies had not been able to observe every step of the process and often required artificial stirring of the solutions.

The results stunned the researchers. While the acids did diffuse across a lipid membrane, they did so at rates that were diametrically opposite to the predictions of the Rule, i.e. the most lipophilic molecules were actually transported slowest. The researchers studied four acids (acetic, butanoic, valeric, and hexanoic) that had increasingly larger "acyl" (or carbon) chains. The longer the carbon chain, the easier the chemical dissolves in lipids and, therefore, according to Overton, the faster they should diffuse across a lipid membrane. In fact, the University of Warwick researchers observed that for these four acids the exact opposite is true: the easier it is for an acid to dissolve in a lipid, the slower it is transported across the membrane.

The research team will now use their technique to examine the diffusion into cells of a range of other chemicals. The lead researcher on the study from the University of Warwick, Professor Patrick Unwin, said: "This was a surprising and exciting finding. Our direct observations appear to totally undermine a key rule that has withstood the test of time for over a century. We will now make observations with a range of other chemicals, and with other techniques, to further elucidate the molecular basis for our observations. Text books will have to be rewritten to revise a rule that has been relied on for over a century. Advanced techniques, such as the one we have developed, should give much clearer insight into the action of a wide range of drug molecules, which will be of significant interest to drug developers."


Story Source:

The above story is based on materials provided by University of Warwick. Note: Materials may be edited for content and length.


Journal Reference:

  1. John M. A. Grime, Martin A. Edwards, Nicola C. Rudd and Professor Patrick R. Unwin. Quantitative visualization of passive transport across bilayer lipid membranes. Proceedings of the National Academy of Sciences, August 26, 2008

Cite This Page:

University of Warwick. "Century-old Rule Of Chemistry Overturned -- Major Implications For Drug Delivery." ScienceDaily. ScienceDaily, 25 August 2008. <www.sciencedaily.com/releases/2008/08/080825174959.htm>.
University of Warwick. (2008, August 25). Century-old Rule Of Chemistry Overturned -- Major Implications For Drug Delivery. ScienceDaily. Retrieved July 24, 2014 from www.sciencedaily.com/releases/2008/08/080825174959.htm
University of Warwick. "Century-old Rule Of Chemistry Overturned -- Major Implications For Drug Delivery." ScienceDaily. www.sciencedaily.com/releases/2008/08/080825174959.htm (accessed July 24, 2014).

Share This




More Matter & Energy News

Thursday, July 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

TSA Administrator on Politics and Flight Bans

TSA Administrator on Politics and Flight Bans

AP (July 24, 2014) — TSA administrator, John Pistole's took part in the Aspen Security Forum 2014, where he answered questions on lifting of the ban on flights into Israel's Tel Aviv airport and whether politics played a role in lifting the ban. (July 24) Video provided by AP
Powered by NewsLook.com
Creative Makeovers for Ugly Cellphone Towers

Creative Makeovers for Ugly Cellphone Towers

AP (July 24, 2014) — Mobile phone companies and communities across the country are going to new lengths to disguise those unsightly cellphone towers. From a church bell tower to a flagpole, even a pencil, some towers are trying to make a point. (July 24) Video provided by AP
Powered by NewsLook.com
Algonquin Power Goes Activist on Its Target Gas Natural

Algonquin Power Goes Activist on Its Target Gas Natural

TheStreet (July 23, 2014) — When The Deal's Amanda Levin exclusively reported that Gas Natural had been talking to potential suitors, the Ohio company responded with a flat denial, claiming its board had not talked to anyone about a possible sale. Lo and behold, Canadian utility Algonquin Power and Utilities not only had approached the company, but it did it three times. Its last offer was for $13 per share as Gas Natural's was trading at a 60-day moving average of about $12.50 per share. Now Algonquin, which has a 4.9% stake in Gas Natural, has taken its case to shareholders, calling on them to back its proposals or, possibly, a change in the target's board. Video provided by TheStreet
Powered by NewsLook.com
Robot Parking Valet Creates Stress-Free Travel

Robot Parking Valet Creates Stress-Free Travel

AP (July 23, 2014) — 'Ray' the robotic parking valet at Dusseldorf Airport in Germany lets travelers to avoid the hassle of finding a parking spot before heading to the check-in desk. (July 23) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

    Health News

      Environment News

        Technology News



          Save/Print:
          Share:  

          Free Subscriptions


          Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

          Get Social & Mobile


          Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

          Have Feedback?


          Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
          Mobile iPhone Android Web
          Follow Facebook Twitter Google+
          Subscribe RSS Feeds Email Newsletters
          Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins