Diffusion-ordered Spectroscopy Research Articles

NMR relaxometric probing of ionic liquid dynamics and diffusion under mesoscopic confinement within bacterial cellulose ionogels.

Bacterial cellulose ionogels (BCIGs) represent a new class of material comprising a significant content of entrapped ionic liquid (IL) within a porous network formed from crystalline cellulose microfibrils. BCIGs suggest unique opportunities in separations, optically active materials, solid electrolytes, and drug delivery due to the fact that they can contain as much as 99% of an IL phase by weight, coupled with an inherent flexibility, high optical transparency, and the ability to control ionogel cross-sectional shape and size. To allow for the tailoring of BCIGs for a multitude of applications, it is necessary to better understand the underlying principles of the mesoscopic confinement within these ionogels. Toward this, we present a study of the structural, relaxation, and diffusional properties of the ILs, 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([emim][Tf2N]) and 1-butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide ([bmpy][Tf2N]), using 1H and 19F NMR T1 relaxation times, rotational correlation times, and diffusion ordered spectroscopy (DOSY) diffusion coefficients, accompanied by molecular dynamics (MD) simulations. We observed that the cation methyl groups in both ILs were primary points of interaction with the cellulose chains and, while the pore size in cellulose is rather large, [emim]+ diffusion was slowed by ∼2-fold, whereas [Tf2N]- diffusion was unencumbered by incorporation in the ionogel. While MD simulations of [bmpy][Tf2N] confinement at the interface showed a diffusion coefficient decrease roughly 3-fold compared to the bulk liquid, DOSY measurements did not reveal any significant changes in diffusion. This suggests that the [bmpy][Tf2N] alkyl chains dominate diffusion through formation of apolar domains. This is in contrast to [emim][Tf2N] where delocalized charge appears to preclude apolar domain formation, allowing interfacial effects to be manifested at a longer range in [emim][Tf2N].

Nuclear Magnetic Resonance Spectroscopy

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Structure and dynamics of propylammonium nitrate-acetonitrile mixtures: An intricate multi-scale system probed with experimental and theoretical techniques.

In this article, we report the study of structural and dynamical properties for a series of acetonitrile/propylammonium nitrate mixtures as a function of their composition. These systems display an unusual increase in intensity in their X-ray diffraction patterns in the low-q regime, and their 1H-NMR diffusion-ordered NMR spectroscopy (DOSY) spectra display unusual diffusivities. However, the magnitude of both phenomena for mixtures of propylammonium nitrate is smaller than those observed for ethylammonium nitrate mixtures with the same cosolvent, suggesting that the cation alkyl tail plays an important role in these observations. The experimental X-ray scattering data are compared with the results of molecular dynamics simulations, including both ab initio studies used to interpret short-range interactions and classical simulations to describe longer range interactions. The higher level calculations highlight the presence of a strong hydrogen bond network within the ionic liquid, only slightly perturbed even at high acetonitrile concentration. These strong interactions lead to the symmetry breaking of the NO3- vibrations, with a splitting of about 88 cm-1 in the ν3 antisymmetric stretch. The classical force field simulations use a greater number of ion pairs, but are not capable of fully describing the longest range interactions, although they do successfully account for the observed concentration trend, and the analysis of the models confirms the nano-inhomogeneity of these kinds of samples.

Analysis of Polycyclic Aromatic Hydrocarbon (PAH) Mixtures Using Diffusion-Ordered NMR Spectroscopy and Adsorption by Powdered Activated Carbon and Biochar.

Analysis of polycyclic aromatic hydrocarbons (PAHs) in air and water sources is a key part of environmental chemistry research, since most PAHs are well known to be associated with negative health impacts on humans. This study explores an approach for analyzing PAH mixtures with advanced nuclear magnetic resonance (NMR) spectroscopic techniques including high-resolution one-dimensional (1D) NMR spectroscopy and diffusion-ordered NMR spectroscopy (DOSY NMR). With this method, different kinds of PAHs can be detected and differentiated from a mixture with high resolution. The adsorption process of PAH mixtures by PAC and biochar was studied to understand the mechanism and assess the method.

Improving reliability of chemometric models for authentication of species origin of heparin by switching from 1D to 2D NMR experiments

Nuclear magnetic resonance (NMR) spectroscopy is regarded as one of the most powerful and versatile analytical approaches to assure the quality of heparin preparations. In particular, it was recently demonstrated that by using 1H NMR coupled with chemometrics heparin and low molecular weight heparin (LMWH) samples derived from three major animal species (porcine, ovine and bovine) can be differentiated [Y.B. Monakhova et al. J. Pharm. Anal. 149 (2018) 114–119].In this study, significant improvement of existing chemometric models was achieved by switching to 2D NMR experiments (heteronuclear multiple-quantum correlation (HMQC) and diffusion-ordered spectroscopy (DOSY)). Two representative data sets (sixty-nine heparin and twenty-two LMWH) belonged to different batches and distributed by different commercial companies were investigated. A trend for animal species differentiation was observed in the principal component analysis (PCA) score plot built based on the DOSY data. A superior model was constructed using HMQC experiments, where individual heparin (LMWH) clusters as well as their blends were clearly differentiated. The predictive power of different classification methods as well as unsupervised techniques (independent components analysis, ICA) clearly proved applicability of the model for routine heparin and LMWH analysis.The switch from 1D to 2D NMR techniques provides a wealth of additional information, which is beneficial for multivariate modeling of NMR spectroscopic data for heparin preparations.

Elucidating the Solution-Phase Structure and Behavior of 8-Hydroxyquinoline Zinc in DMSO.

The solution-phase structure and electronic relaxation dynamics of zinc bis-8-hydroxyquinoline [Zn(8HQ)2] in dimethyl sulfoxide (DMSO) were examined using a broad array of spectroscopic techniques, complimented by ab initio calculations of molecular structure. The ground-state structure was determined using extended X-ray absorption fine structure (EXAFS) data collected on the Zn K-edge and diffusion ordered spectroscopy (DOSY) NMR. The complex was found to be monomeric and octahedral, with two bidentate 8-hydroxyquinolate ligands and two DMSO molecules coordinated to the zinc through oxygen atoms. Electronic relaxation dynamics were examined with ultrafast transient absorption spectroscopy and complementary density functional calculations. Electronic relaxation was observed to proceed through both singlet and triplet pathways. This solution-phase data provides a deeper physical understanding of the behavior of this molecule, which has a variety of uses such as sensing, OLEDs, and biological applications.

Effect of Cation–π Interaction on Macroionic Self‐Assembly

AbstractA series of rod‐shaped polyoxometalates (POMs) [Bu4N]7[Mo6O18NC(CH2O)3MnMo6O18(OCH2)3CNMo6O18] and [Bu4N]7[ArNMo6O17NC(CH2O)3MnMo6O18(OCH2)3CNMo6O17NAr] (Ar=2,6‐dimethylphenyl, naphthyl and 1‐methylnaphthyl) were chosen to study the effects of cation–π interaction on macroionic self‐assembly. Diffusion ordered spectroscopy (DOSY) and isothermal titration calorimetry (ITC) techniques show that the binding affinity between the POMs and Zn2+ ions is enhanced significantly after grafting aromatic groups onto the clusters, leading to the effective replacement of tetrabutylammonium counterions (TBAs) upon the addition of ZnCl2. The incorporation of aromatic groups results in the significant contribution of cation–π interaction to the self‐assembly, as confirmed by the opposite trend of assembly size vs. ionic strength when compared with those without aromatic groups. The small difference between two aromatic groups toward the Zn2+ ions is amplified after combining with the clusters, which consequently triggers the self‐recognition behavior between two highly similar macroanions.

Effect of Cation-π Interaction on Macroionic Self-Assembly.

A series of rod-shaped polyoxometalates (POMs) [Bu4 N]7 [Mo6 O18 NC(CH2 O)3 MnMo6 O18 (OCH2 )3 CNMo6 O18 ] and [Bu4 N]7 [ArNMo6 O17 NC(CH2 O)3 MnMo6 O18 (OCH2 )3 CNMo6 O17 NAr] (Ar=2,6-dimethylphenyl, naphthyl and 1-methylnaphthyl) were chosen to study the effects of cation-π interaction on macroionic self-assembly. Diffusion ordered spectroscopy (DOSY) and isothermal titration calorimetry (ITC) techniques show that the binding affinity between the POMs and Zn2+ ions is enhanced significantly after grafting aromatic groups onto the clusters, leading to the effective replacement of tetrabutylammonium counterions (TBAs) upon the addition of ZnCl2 . The incorporation of aromatic groups results in the significant contribution of cation-π interaction to the self-assembly, as confirmed by the opposite trend of assembly size vs. ionic strength when compared with those without aromatic groups. The small difference between two aromatic groups toward the Zn2+ ions is amplified after combining with the clusters, which consequently triggers the self-recognition behavior between two highly similar macroanions.

Exploring Strategies To Bias Sequence in Natural and Synthetic Oligomers and Polymers.

Millions of years of biological evolution have driven the development of highly sophisticated molecular machinery found within living systems. These systems produce polymers such as proteins and nucleic acids with incredible fidelity and function. In nature, the precise molecular sequence is the factor that determines the function of these macromolecules. Given that the ability to precisely define sequence emerges naturally, the fact that biology achieves unprecedented control over the unit sequence of the monomers through evolved enzymatic catalysis is incredible. Indeed, the ability to engineer systems that allow polymer synthesis with precise sequence control is a feat that technology is yet to replicate in artificial synthetic systems. This is the case because, without access to evolutionary control for finely tuned biological catalysts, the inability to correct errors or harness multiple competing processes means that the prospects for digital control of polymerization have been firmly bootstrapped to biological systems or limited to stepwise synthetic protocols. In this Account, we give an overview of strategies that have been used over the last 5 years in efforts to program polymer synthesis with sequence control in the laboratory. We also briefly explore how the use of robotics, algorithms, and stochastic chemical processes might lead to new understanding, mechanisms, and strategies to achieve full digital control. The aim is to see whether it is possible to go beyond bootstrapping to biological polymers or stepwise chemical synthesis. We start by describing nonenzymatic techniques used to obtain sequence-controlled natural polymers, a field that lends itself to direct application of insights gleaned from biology. We discuss major advances, such as the use of rotaxane-based molecular machines and templated approaches, including the utilization of biological polymers as templates for purely synthetic chains. We then discuss synthetic polymer chemistry, whose array of techniques allows the production of polymers with enormous structural and functional diversity, but so far with only limited control over the unit sequence itself. Synthetic polymers can be subdivided into multiple classes depending on the nature of processes used to synthesize them, such as by addition or condensation. Consequently, varied approaches for sequence control have been demonstrated in the area, including but not limited to click reactions, iterative solid-phase chemistry, and exploiting the chemical affinity of the monomers themselves. In addition to those, we highlight the importance of environmental bias in possible control of polymerization at the single-unit level, such as using catalyst switching or external stimuli. Even the most successful experimental sequence control approach needs appropriate tools to verify its scope and validity; therefore, we devote part of the present Account to possible analytical approaches to sequence readout, starting with well-established tandem mass spectrometry techniques and touching on those more applicable to specific classes of processes, such as diffusion-ordered NMR spectroscopy. Finally, we discuss progress in modeling and automation of sequence-controlled polymers. We postulate that developments in analytical chemistry, bioinformatics, and computer modeling will lead to new ways of exploring the development of new strategies for the realization of sequence control by means of sequence bias. This is the case because treating the assembly of polymers as a network of chemical reactions will enable the development of control strategies that can bias the outcome of the polymer assembly. The grand aim would be the synthesis of complex polymers in one step with a precisely defined digital sequence.

Biodegradable PHB from rac-β-Butyrolactone: Highly Controlled ROP Mediated by a Pentacoordinated Aluminum Complex

The diphenoxyimine five-coordinated aluminum complex [AlMeL2] (1), (L = N-(2,6-diisopropylphenyl)phenoxyimine), has been synthesized and fully characterized. The mononuclear structure observed in the solid state by X-ray diffraction analysis is maintained in solution, as shown by diffusion-ordered NMR spectroscopy (DOSY). Complex 1 is an active ROP catalyst able to provide well-controlled living ring-opening polymerization of rac-BBL at 100 °C, with PDI = 1.03, in the presence of BnOH to give the biodegrable polyester poly(hydroxybutyrate) (PHB). The suggested active species of this catalytic process, the aluminum complex [Al(OBn)L2] (2), has been synthesized and fully characterized. DFT calculations have been carried out to study the influence of the catalytic active species pocket over the polymer molecular weight control. Moreover, 1 is also active in the copolymerization of rac-β-butyrolactone and l-lactide to provide random copolymers.

DOSY Plus Selective TOCSY: An Efficient NMR Combination for Analyzing Hydrogenation/Hydrogenolysis Mixtures of Biomass-Derived Platform Compounds

Analyzing the mixtures obtained from hydrogenation or hydrogenolysis reactions of biomass-derived platform chemicals is challenging work. With the development and improvement of NMR techniques, the NMR spectrometer proves to be an alternative and highly efficient piece of equipment for the rapid analysis of complex mixtures without the need for tedious purification. Herein, diffusion-ordered spectroscopy (DOSY) is applied in analyzing four model mixtures, which consist of the reactants and products from hydrogenation/hydrogenolysis reactions of biomass-derived platform chemicals. The results show that the DOSY technique can pseudoseparate most components in the model mixtures. The 1D selective gradient TOCSY technique is used as a supporting tool in the cases where the DOSY technique cannot clearly distinguish between the components of the mixtures. This is generally a problem when components in the mixture have very similar diffusion coefficients or severe overlap of peaks. The results show that DOSY and...

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 generalized to cover a range of solvents and temperatures.

Higher-generation type III-B rotaxane dendrimers with controlling particle size in three-dimensional molecular switching

Type III-B rotaxane dendrimers (T3B-RDs) are hyperbranched macromolecules with mechanical bonds on every branching unit. Here we demonstrate the design, synthesis, and characterization of first to third (G1–G3), and up to the fourth (G4) generation (MW > 22,000 Da) of pure organic T3B-RDs and dendrons through the copper-catalyzed alkyne–azide cycloaddition (CuAAC) reaction. By utilizing multiple molecular shuttling of the mechanical bonds within the sphere-like macromolecule, a collective three-dimensional contract-extend molecular motion is demonstrated by diffusion ordered spectroscopy (DOSY) and atomic force microscopy (AFM). The discrete T3B-RDs are further observed and characterized by AFM, dynamic light scattering (DLS), and mass spectrometry (MS). The binding of chlorambucil and pH-triggered switching of the T3B-RDs are also characterized by 1H-NMR spectroscopy.

Determination of the Molecular Weight of Conjugated Polymers with Diffusion-Ordered NMR Spectroscopy

Size exclusion chromatography (SEC) is not well suited for characterizing the molecular weight (MW) and MW distribution of conjugated polymers, especially those that absorb strongly at the detection wavelengths, or those that interact with and adsorb on the walls of SEC columns. We demonstrate diffusion-ordered NMR spectroscopy (DOSY) as a complementary method for characterizing the size and size distribution of conjugated polymers. Starting with four batches of poly(3-hexylthiophene), whose distinct and narrow MW distributions had been fully characterized, as a model system, we establish a power-law relationship between the weight-average MW and the diffusion coefficient measured through DOSY. We extend this approach to characterizing poly[4-(4,4-dihexadecyl-4H-cyclopenta[1,2-b:5,4-b′]dithiophen-2-yl)-alt-[1,2,5]thiadiazolo-[3,4-c]pyridine], whose absorption properties preclude its characterization with light scattering based techniques, including SEC. By applying the same power law on the diffusion coef...

A Constrained Tetrapeptide as a Model of Cu(I) Binding Sites Involving Cu4S6 Clusters in Proteins.

Peptide design is an efficient strategy to create relevant models of natural metal binding sites found in proteins. The two short tetrapeptides Ac-Cys-dPro-Pro-Cys-NH2 (CdPPC) and Ac-Cys-Pro-Gly-Cys-NH2 (CPGC) were synthesized and studied as mimics of Cu(I) binding sites involved in Cu homeostasis. Both sequences contain β turn inducing motifs to rigidify the peptide backbone structure and thereby preorganize the metal-binding side chains. The more constrained structure of the peptide CdPPC with respect to CPGC was evidenced by the measurements of the temperature coefficients of the amide protons by 1H NMR, which suggest a solvent-shielded intramolecular hydrogen bond in CdPPC, and no H-bond in CPGC. The Cu(I) complexes were studied by UV, circular dichroism (CD), and NMR spectroscopies as well as electrospray ionization mass spectrometry (ESI-MS) experiments in aqueous solution at physiological pH. The complexes formed with CPGC showed a complicated speciation with the possible formation of many polymetallic species. By contrast, the better preorganization in CdPPC leads to the formation of a unique Cu4L3 complex involving a Cu4S6 core. The formation of this specific cluster was confirmed by ESI-MS and by diffusion-ordered NMR spectroscopy in solution. The affinity of CdPPC for Cu(I) (β11pH7.4 = 1017.5 calculated for a CuL complex) is more than 1 order of magnitude larger than the affinity measured for the less constrained peptide CPGC. Besides, this stability constant value is very similar to those reported with proteins. Therefore, the Cu(I) complex formed with the simple tetrapeptide CdPPC in water at physiological pH represents a very good model of Cu(I)-thiolate clusters found in proteins. The extremely large selectivity (1011) in favor of Cu(I) with respect to Zn(II), an abundant competitor in cells, makes it a promising candidate to be targeted to the liver cells for the localized treatment of Cu overload in Wilson's disease.

Diffusion-Ordered Spectroscopy Nuclear Magnetic Resonance as an Alternative Technique to Improve Asphaltene Characterization

An asphaltene sample from a light Arabian crude oil was characterized using several analytical techniques, such as thermogravimetric analysis, nuclear magnetic resonance, Fourier transform infrared spectroscopy, and elemental analysis. The results showed that the sample has a high sulfur content and highly condensed aromatic compounds and the average molecular structure is predominantly of continental/island type; however, the presence of a significant amount of methylene carbons in long alkyl chains is clear. A diffusion-ordered spectroscopy nuclear magnetic resonance experiment (DOSY-NMR) was carried out to detect the presence of asphaltene aggregates, evaluate their size, and shed light on the presence of maltenic occluded species and entrained residual solvent. In the DOSY spectrum, some sample signals were attributed to non-asphaltenic molecules, showing that it is possible to achieve key features of the sample complexity in “one shot”.

Automatic differential analysis of NMR experiments in complex samples.

Liquid state nuclear magnetic resonance (NMR) is a powerful tool for the analysis of complex mixtures of unknown molecules. This capacity has been used in many analytical approaches: metabolomics, identification of active compounds in natural extracts, and characterization of species, and such studies require the acquisition of many diverse NMR measurements on series of samples. Although acquisition can easily be performed automatically, the number of NMR experiments involved in these studies increases very rapidly, and this data avalanche requires to resort to automatic processing and analysis. We present here a program that allows the autonomous, unsupervised processing of a large corpus of 1D, 2D, and diffusion-ordered spectroscopy experiments from a series of samples acquired in different conditions. The program provides all the signal processing steps, as well as peak-picking and bucketing of 1D and 2D spectra, the program and its components are fully available. In an experiment mimicking the search of a bioactive species in a natural extract, we use it for the automatic detection of small amounts of artemisinin added to a series of plant extracts and for the generation of the spectral fingerprint of this molecule. This program called Plasmodesma is a novel tool that should be useful to decipher complex mixtures, particularly in the discovery of biologically active natural products from plants extracts but can also in drug discovery or metabolomics studies.

Bipyrrolidine salan alkoxide complexes of lanthanides: synthesis, characterisation, activity in the polymerisation of lactide and mechanistic investigation by DOSY NMR.

Four dimeric lanthanide alkoxide complexes bearing ONNO bipyrrolidine salan ligands (LMeH2/LtBuH2) have been prepared with Nd, Sm and Yb. Depending on the metal and substituents, these complexes adopt varying coordination geometries. While investigating the hydrolytic degradation of these complexes, three dimeric mixed alkoxide/hydroxide and bis-hydroxide products were also prepared, isolated and characterised. Despite paramagnetism, 1H NMR and diffusion ordered spectroscopy (DOSY) allowed additional characterisation alongside elemental and single-crystal X-ray diffraction analyses. These systems were very active for the controlled ring-opening polymerisation (ROP) of rac-lactide (LA), under industrially relevant melt conditions and in solution, yielding complete conversion within 5 minutes at [Ln] : [LA] ratios of up to 3000 : 1 in toluene, and at 80 °C, whilst retaining low dispersities (Đ = 1.1). 1H DOSY NMR spectroscopy was employed to monitor polymer growth from the metal centres in situ, and revealed a dinuclear catalytically active species.

Physicochemical Properties of α-Form Hydrated Crystalline Phase of 3-(10-Carboxydecyl)-1,1,1,3,5,5,5-heptamethyl Trisiloxane/Higher alcohol/Polyoxyethylene (5 mol) Glyceryl monostearate/Water System.

The α-form hydrated crystalline phase (often called as an α-gel) is one of the hydrated crystalline phases which can be exhibited by surfactants and lipids. In this study, a novel system of an α-form hydrated crystal was developed, composed of 3-(10-carboxydecyl)-1,1,1,3,5,5,5-heptamethyl trisiloxane (CDTS), polyoxyethylene (5 mol) glyceryl monostearate (GMS-5), higher alcohol. This is the first report to indicate that a silicone surfactant can form an α-form hydrated crystal. The physicochemical properties of this system were characterized by small and wide angle X-ray scattering (SWAXS), differential scanning calorimetry (DSC), and diffusion-ordered NMR spectroscopy (DOSY) experiments. SWAXS and DSC measurements revealed that a plurality of crystalline phases coexist in the CDTS/higher alcohol/water ternary system. By adding GMS-5 to the ternary system, however, a wide region of a single α-form hydrated crystalline phase was obtained. The self-diffusion coefficients (Dsel) from the NMR measurements suggested that all of the CDTS, GMS-5, and higher alcohol molecules were incorporated into the same α-form hydrated crystals.

Spatially encoded diffusion-ordered NMR spectroscopy of reaction mixtures in organic solvents.

Diffusion-ordered NMR spectroscopy (DOSY) is a powerful method for the analysis of mixtures. Classic DOSY methods require several minutes of acquisition, and we show here that DOSY experiments can be recorded in less than one second for the challenging case of solution mixtures in low-viscosity solvents. The proposed method relies on a spatial encoding of the diffusion dimension, for which convection-compensation and spectral-selection strategies are introduced. The method is illustrated with the analysis of a reaction mixture, and more accurate estimates of the diffusion coefficients are obtained.