Issue 22, 2011
From the journal:

Organic & Biomolecular Chemistry

Comparison of diffusion coefficients for matched pairs of macrocyclic and linear molecules over a drug-like molecular weight range†

Andrew R. Bogdan,a   Nichola L. Daviesb  and  Keith James*a  

* Corresponding authors

a Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California, USA
E-mail: kjames@scripps.edu
Fax: +1 858 784 7550
Tel: +1 858 784 2507

b Pfizer Worldwide Research, Sandwich, Kent, UK

Abstract

The diffusion coefficients of a series of closely matched pairs of macrocyclic and linear molecules have been compared using NMR spectroscopy. The macrocyclic series was designed both to overlap with and extend beyond the molecular weight range typically employed for drug-like molecules. The linear molecules each represent a carbogenic fission of their macrocyclic counterparts, designed to minimize differences in functionality and physicochemical properties. Each series of molecules was prepared using copper catalyzed azide-alkyne cycloaddition (CuAAC) reactions conducted in a flow using a copper tube. The macrocyclic series exhibited consistently higher diffusion across the entire molecular weight range studied. The fold difference in diffusion coefficients between the macrocyclic and linear analogues appeared to be independent of either solvent viscosity or dielectric environment.

Graphical abstract: Comparison of diffusion coefficients for matched pairs of macrocyclic and linear molecules over a drug-like molecular weight range

About
Cited by
Related
Download options Please wait...

Supplementary files

Article information

DOI
https://doi.org/10.1039/C1OB05996C
Article type
Paper
Submitted
20 Jun 2011
Accepted
05 Sep 2011
First published
05 Sep 2011

Org. Biomol. Chem., 2011,9, 7727-7733

Permissions

Request permissions

Comparison of diffusion coefficients for matched pairs of macrocyclic and linear molecules over a drug-like molecular weight range

A. R. Bogdan, N. L. Davies and K. James, Org. Biomol. Chem., 2011, 9, 7727 DOI: 10.1039/C1OB05996C

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements