Improving the Interpretation of Small Molecule Diffusion Coefficients

Diffusion-ordered NMR spectroscopy (DOSY) is increasingly widely used for the analysis of mixtures by NMR spectroscopy, dispersing the signals of different species according to their diffusion coefficients. DOSY is used primarily to distinguish between the signals of different species, with the interpretation of the diffusion coefficients observed usually being purely qualitative, for example to deduce whether one species is bigger or smaller than another. In principle the actual values of diffusion coefficient obtained carry important information about the sizes of different species and on interactions between species, but the relationship between diffusion coefficient and molecular mass is in general a very complex one. Here a recently-proposed analytical relationship between diffusion coefficient and molecular mass for the restricted case of small organic molecules is tested against a wide range of data from the scientific literature, and generalised to cover a range of solvents and temperatures

DOSY experiments using 19F NMR for the study of complex mixtures

Orientador: Cláudio Francisco TormenaDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de QuímicaResumo: DOSY ("Espectroscopia de Difusão Ordenada") baseia-se na capacidade de separação de sinais de compostos diferentes de acordo com o seu coeficiente de difusão, e por isto, dificuldades surgem quando sinais se sobrepõem ou quando os compostos possuem tamanhos muito semelhantes. O que é uma situação muito comum em análises de soluções de isômeros ou quando espécies quimicamente semelhantes estão presentes. A sobreposição de sinais pode ser evitada pelo uso de um núcleo diferente do tradicional 1H, tal como o 19F, cujos espectros possuem uma gama espectral grande, o que tipicamente leva a sinais bem resolvidos. Quanto aos componentes de tamanho semelhante, o progresso em MAD ("DOSY Auxiliado por Matriz") solucionou este problema e reforçou o DOSY como uma ferramenta poderosa. MAD dá ao analista o poder de manipular o comportamento de difusão dos compostos, por interação com uma matriz, geralmente um agente surfactante ou um agente de complexação, que interage diferente com cada componente da mistura. Aqui se demonstra a utilização de uma sequência de pulsos de 19F DOSY para vários benzenos fluorados. Para os compostos com constantes de acoplamento nJFF, a "modulação devido ao J" pode ser suprimida usando a sequência Oneshot45. Também se avalia a eficiência de micelas de SDS e AOT como agentes de separação para soluções dos isômeros de fluorfenóis e fluoranilinas. O sitio de interação, entre solutos e surfactantes, foram investigados utilizando experimentos medindo o efeito Overhauser nuclear. 19F MAD fornece uma ferramenta poderosa para a análise de misturas, com o potencial de ser muito útil para o estudo de medicamentos, em particular, no estudo de degradação de fármacosAbstract: DOSY (Diffusion-Ordered Spectroscopy) analysis is based on the ability to separate signals from different compounds depending on their diffusion coefficient, and can therefore struggle when NMR signals overlap or when the compounds are of very similar size. This is naturally a common situation in drug analysis, where isomers and other chemically similar species are present. Signal overlap can be avoided by using a nucleus such as 19F instead of the traditional 1H, because 19F NMR spectra are typically very sparse and have a much larger spectral range, leading to well-resolved signals. As for the similar size components, developments in "Matrix-Assisted DOSY" (MAD) have alleviated this problem and further strengthened DOSY as a powerful tool. MAD gives the analyst the power to manipulate diffusion behaviour by differential interaction with a matrix, commonly a surfactant or a complexation agent, binding differently with the each component of the mixture. Here, we demonstrate the use of a modified 19F DOSY experiment for various fluorinated benzenes. For compounds with significant nJFF coupling constants, as is common, the undesirable "J-modulation" can be efficiently suppressed using the Oneshot45 pulse sequence. We have also evaluate the efficiency of SDS (normal) and AOT (reverse) micelles as separation agents for mixtures containing positional isomers of fluorophenols and fluoroanilines using 19F MAD. The interaction sites between solutes and surfactants were investigated using different Nuclear Overhauser Effect experiments. 19F MAD provides a powerful tool for mixture analysis by NMR with the potential to be very useful for the study of pharmaceutical formulations, in particular in the study of drug degradationMestradoQuimica OrganicaMestre em QuímicaCNP

SCALPEL 3D

i) TopSpin files a) AU program: setscalpelpars b) Pulse sequence for BRUKER: SCALPEL_it2 c) Pulse sequence for BRUKER: SCALPEL_idiff d) Pulse sequence for BRUKER: gdp_2dsel_it2_dipsi e) Pulse sequence for BRUKER: gdp_2dsel_idiff_dipsi ii) SCALPEL data (BRUKER format) a)Glucose, glucose-6-phosphate and maltose, in D2O (FOLDER Glucose_gluc6P_maltose) 1 - 1H 2 - 2D 1H Oneshot45, with water pre-saturation 3 - 2D 1H iDESTO, with water pre-saturation 4 - 1H selective TOCSY 5 - 3D SCALPEL (using TOCSY-t1 and diffusion) b)Lactose and melibiose, in D2O (FOLDER Lactose_melibiose) 1 - 1H 2 - 2D 1H iREST2, with water pre-saturation 3 - 2D SCALPEL (first increment of TOCSY-t1 and relaxation decay), with water pre-saturation 4 - 3D SCALPEL (using TOCSY-t1 and relaxation), with water pre-saturation c)Mackeson Stout, with 20% added D2O (FOLDER Stout_20%D2O) 1 - 1H 2 - 2D 1H Oneshot45, with water pre-saturation 3 - 2D 1H iDESTO with, water pre-saturation 4 - 1H, with water pre-saturation 5 - {1H}13C 6 - 2D EA-HSQC 7 - 2D EA-HSQC-TOCSY 8 - 3D SCALPEL (using TOCSY-t1 and diffusion) 9 - 3D SCALPEL (using TOCSY-t1 and relaxation) 10 - 1H selective TOCSY 11 - 3D SCALPEL (using TOCSY-t1 and diffusion), with water pre-saturatio

MAGNATE

i) Current version of MAGNATE Matlab version (beta, 18 June 2018) ii) 3D Oneshot-HSQC data for mixture of B vitamins (MAGNATE format) iii) NMR data for mixture of B vitamins (BRUKER format) Folder - Experiment 1 - 1H 2 - {1H}13C 3 - 2D Echo/Antiecho-HSQC with spectrum aliasing 4 - 2D DOSY-Oneshot45 8 - 3D Oneshot-HSQC with spectrum aliasing iv) NMR data for mixture of rutin and quercetin (BRUKER format) Folder - Experiment 1 - 1H 2 - {1H}13C 3 - 2D EA-HSQC with spectrum aliasing 4 - 3D Oneshot-HSQC with spectrum aliasing v) 3D Oneshot-HSQC pulse sequence (BRUKER

A new tool for NMR analysis of complex systems:selective pure shift TOCSY

A new NMR experiment aids the identification of components in complex systems, including mixtures.</p

Dissect and Divide: Putting NMR spectra of mixtures under the knife

Efficient, practical, and nondestructive analysis of complex mixtures is vital in many branches of chemistry. Here we present a new type of NMR experiment that allows the study of very challenging intact mixtures, in which subspectra of individual components can be extracted when other NMR means fail, for the case of a single, intact, static (constant composition) sample. We demonstrate the new approach, SCALPEL (Spectral Component Acquisition by Localized PARAFAC Extraction of Linear components), on a natural fermented beverage, beer, and other carbohydrate mixtures, obtaining individual carbohydrate component subspectra. This new class of NMR experiment is based on dissecting the spectrum rather than the sample, using pulse sequences tailored to generate data suitable for powerful tensor decomposition methods to allow highly complex spectra to be analyzed stepwise, one small section at a time. It has the clear potential to attack problems beyond the reach of current methods