DOSY NMR Experiments as a Tool for the Analysis of Constitutional and Motional Dynamic Processes: Implementation for the Driven Evolution of Dynamic Combinatorial Libraries of Helical Strands

Giuseppone, Nicolas; Schmitt, Jean‐Louis; Allouche, Lionel; Lehn, Jean‐Maríe

doi:10.1002/anie.200703168

Cited by 87 publications

(54 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[44][45][46][47][48][49] Namely, a measurement of self-diffusion coefficient (SDC), e.g., by 2D DOSY method that combines the advantages of high-resolution NMR spectroscopy with diffusivity data, could be of use.…”

Section: Resultsmentioning

confidence: 99%

Structure, Conformation, and Dynamics of P,N-Containing Cyclophanes in Solution

et al. 2010

View full text Add to dashboard Cite

3D structures in solution of highly symmetrical N,P-containing macrocycles were established by a variety of 2D NMR correlation techniques. It was shown that a number of magnetically equivalent fragments in such symmetrical systems can be estimated by NMR diffusion measurement. The title compounds adopt a helical conformation of the macrocycles in solution. The extent of twisting and the size of the intramolecular cavity are determined by steric hindrance of the aromatic substituents on the exocyclic phosphorus atoms with phenylene and dimethylmethylene groups forming the macrocycle. In solution these macrocycles host aromatic guests inside the cavity.

show abstract

Section: Resultsmentioning

confidence: 99%

Structure, Conformation, and Dynamics of P,N-Containing Cyclophanes in Solution

et al. 2010

View full text Add to dashboard Cite

show abstract

“…While good results have been obtained by mass spectrometric analysis, the most promising techniques are multidimensional, allowing library members to be separated on the basis of two or more orthogonal characteristics. The most commonly used and probably most powerful technique is liquid chromatography -mass spectrometry ( LC -MS ), but also other techniques such a time -resolved heteronuclear single quantum correlation nuclear magnetic resonance ( HSQC NMR ) [6] or diffusion -ordered spectroscopy ( DOSY ) NMR [7] have found application, albeit as yet only in smaller libraries. These techniques are discussed in more detail in Sections 2.2.2 and 2.2.3 .…”

Section: Methodsmentioning

confidence: 99%

“…Two such approaches have been explored: Lehn et al have used DOSY NMR, where the differences in diffusion times of the library members are used as the second dimension [7] , and Jeannerat and Prins et al have used 1 H -13 C -HSQC NMR and also introduced a temporal dimension, by adding different building blocks at different times and monitoring the evolution of the two -dimensional ( 2 -D ) NMR spectrum [6] .…”

Section: Analysis By Nmrmentioning

confidence: 99%

“…This technique was used by Giuseppone et al in a proof -ofprinciple study on a DCL based on scandium trifl ate -mediated hydrazone exchange. After 12 h of data collection they were able to distinguish between fi ve different levels of diffusion rates that were assigned to linear hydrazones of different lengths ( n = 0 -4 in Scheme 2.3 ) [7] . It is encouraging that the relatively small changes in size of the library members were resolvable on the diffusion time axis.…”

Section: Analysis By Nmrmentioning

confidence: 99%

“…Building blocks used to generate a small DCL of linear hydrazides that can adopt helical conformations and that was analyzed by DOSY NMR to reveal fi ve different compounds ( n = 0 -4)[7] .The temporally resolved HSQC approach by Jeannerat and Prins et al has uncovered a wealth of kinetic and thermodynamic data on their small hydrazone DCL, reproduced inFigure 2.2 . The authors started by adding hydrazide B to a solution of hydrazone 10A and analyzed the mixture using HSQC, which is a 2 -D NMR technique in which the 13 C spectrum is plotted on one axis and correlated to the 1 H spectrum on the other axis.…”

mentioning

confidence: 99%

See 2 more Smart Citations

The Practice of Dynamic Combinatorial Libraries: Analytical Chemistry, Experimental Design, and Data Analysis

Otto

2010

Dynamic Combinatorial Chemistry

View full text Add to dashboard Cite

IntroductionDynamic combinatorial chemistry ( DCC ) [1 -3] was originally developed to solve the problem of obtaining compounds with distinctive molecular recognition properties. These could be either ligands for biomolecules or synthetic receptors for small -molecule guests. Obtaining such molecules by a design -and -synthesis approach remains a daunting task; we simply do not suffi ciently understand issues like conformation and cooperation of the many individually weak noncovalent interactions that together determine effi ciency in molecular recognition. In DCC this problem is circumvented by limiting the design to only small fragments, which are assembled into the desired structures under the direction of the molecules themselves. A description of the basic principles of DCC is provided in Chapter 1 . Chapters 3 and 5 in this book provide ample proof that this approach indeed facilitates effi cient access to synthetic receptors and small -molecule ligands alike. The concept of DCC has also been explored in the context of catalyst development (Chapter 4 ) and polymer chemistry (Chapter 6 ).In many of these applications of DCC the purpose is to identify a specifi c molecule with exceptional properties. The dynamic combinatorial library ( DCL ) is then merely a vehicle through which this molecule may be generated and discovered. In a typical experiment a library is prepared by mixing building blocks, and its composition is analyzed in the absence and presence of an added template molecule or some other stimulus. Any compound in the mixture that is signifi cantly amplifi ed upon addition of the template should be a strong binder. This principle still drives much of the work in DCC, but is arguably rather simplistic. DCLs are complex mixtures of species that are interconnected through a set of equilibria and mass balances, and can behave in ways that are not always immediately intuitive, particularly when the focus is on the amplifi cation of individual molecules. In order to fully appreciate the behavior of a DCL it should be regarded in its entirety as a molecular network that strives to attain the lowest overall Gibbs energy. One of the implications is that the extent to which template binding and amplifi cation are correlated can vary, depending in part on how the experiments Dynamic Combinatorial Chemistry. Edited by Joost N. H. Reek and Sijbren Otto

show abstract