Titrations without the Additions: The Efficient Determination of pKa Values Using NMR Imaging Techniques

It can be very informative to acquire NMR spectra of a sample as a function of the solution pH. Examples can be found in the design of host–guest complexes or in the determination of the pKa values of organic molecules. In the conventional procedure, a series of spectra must be recorded and the pH of the sample adjusted manually between successive NMR measurements. As an alternative to this laborious procedure, we demonstrate how controlled pH gradients may be established in 5 mm NMR tubes and analyzed using standard NMR equipment in a “single shot” experiment. Using 1H NMR imaging techniques and a set of NMR pH indicator compounds, we are able to measure the pH of a sample as a function of position along a pH gradient. We are thus able to obtain the necessary set of 1H NMR spectra as a function of pH from a single sample in a single NMR experiment. As proof of concept, we demonstrate how the technique may be employed for the determination of the pKa values of small organic molecules. We are able to measure pKa values from 1 to 11 to within 0.1 units of their literature values. The method is robust to variations in the setting of the pH gradients and can be readily implemented through an automated sample changer

Efficient pKa Determination in a Nonaqueous Solvent Using Chemical Shift Imaging

Efficient pKa Determination in a Nonaqueous Solvent Using Chemical Shift Imagin

Polyanionic Ligand Platforms for Methyl- and Dimethylaluminum Arrays

Trimethylaluminum finds widespread applications in chemical and materials synthesis, most prominently in its partially hydrolyzed form of methylalumoxane (MAO), which is used as a cocatalyst in the polymerization of olefins. This work investigates the sequential reactions of trimethylaluminum with hexaprotic phosphazenes (RNH)6P3N3 (=XH6) equipped with substituents R of varied steric bulk including tert-butyl (1H6), cyclohexyl (2H6), isopropyl (3H6), isobutyl (4H6), ethyl (5H6), propyl (6H6), methyl (7H6), and benzyl (8H6). Similar to MAO, the resulting complexes of polyanionic phosphazenates [XHn]n−6 accommodate multinuclear arrays of [AlMe2]+ and [AlMe]2+. Reactions were monitored by 31P NMR spectroscopy, and structures were determined by single-crystal X-ray diffraction. They included 1H4(AlMe2)2, 1H3(AlMe2)3, 2H3(AlMe2)3, 3(AlMe2)4AlMe, 4H­(AlMe2)5, 4(AlMe2)6, {5H­(AlMe2)4}2AlMe, 5(AlMe2)6, 6(AlMe2)6, {7(AlMe2)4AlMe}2, and 8(AlMe2)6. The study shows that subtle variations of the steric properties of the R groups influence the reaction pathways, levels of aggregation, and fluxional behavior. While [AlMe2]+ is the primary product of the metalation, [AlMe]2+ is utilized to alleviate overcrowding or to aid aggregation. At the later stages of metalation, [AlMe2]+ groups start to scramble around congested sites. The ligands proved to be very robust and extremely flexible, offering a unique platform to study complex multinuclear metal arrangements

Methanol as hydrogen source: transfer hydrogenation of aromatic aldehydes with a rhodacycle

A cyclometalated rhodium complex has been shown to perform highly selective and efficient reduction of aldehydes, deriving the hydrogen from methanol. With methanol as both the solvent and hydrogen donor under mild conditions and an open atmosphere, a wide range of aromatic aldehydes were reduced to the corresponding alcohols, without affecting other functional groups

Using solution state NMR spectroscopy to probe NMR invisible gelators

Supramolecular hydrogels are formed via the self-assembly of gelator molecules upon application of a suitable trigger. The exact nature of this self-assembly process has been widely investigated as a practical understanding is vital for the informed design of these materials. Solution-state NMR spectroscopy is an excellent non-invasive tool to follow the self-assembly of supramolecular hydrogels. However, in most cases the self-assembled aggregates are silent by conventional 1H NMR spectroscopy due to the low mobility of the constituent molecules, limiting NMR spectroscopy to following only the initial assembly step(s). Here, we present a new solution-state NMR spectroscopic method which allows the entire self-assembly process of a dipeptide gelator to be followed. This gelator forms transparent hydrogels by a multi-stage assembly process when the pH of an initially alkaline solution is lowered via the hydrolysis of glucono-δ-lactone (GdL). Changes in the charge, hydrophobicity and relative arrangement of the supramolecular aggregates can be followed throughout the assembly process by measuring the residual quadrupolar couplings (RQCs) of various molecular probes (here, 14NH4+ and isopropanol-d8), along with the NMR relaxation rates of 23Na+. The initially-formed aggregates comprise negatively charged fibrils which gradually lose their charge and become increasingly hydrophobic as the pH falls, eventually resulting in a macroscopic contraction of the hydrogel. We also demonstrate that the in situ measurement of pH by NMR spectroscopy is both convenient and accurate, representing a useful tool for the characterisation of self-assembly processes by NMR

Probing the surface chemistry of self-assembled peptide hydrogels using solution-state NMR spectroscopy

The surface chemistry of self-assembled hydrogel fibres – their charge, hydrophobicity and ion-binding dynamics – is recognised to play an important role in determining how the gels develop as well as their suitability for different applications. However, to date there are no established methodologies for the study of this surface chemistry. Here, we demonstrate how solution-state NMR spectroscopy can be employed to measure the surface chemical properties of the fibres in a range of hydrogels formed from N-functionalised dipeptides, an effective and versatile class of gelator that has attracted much attention. By studying the interactions with the gel fibres of a diverse range of probe molecules and ions, we can simultaneously study a number of surface chemical properties of the NMR invisible fibres in an essentially non-invasive manner. Our results yield fresh insights into the materials. Most notably, gel fibres assembled using different tiggering methods bear differing amounts of negative charge as a result of a partial deprotonation of the carboxylic acid groups of the gelators. We also demonstrate how chemical shift imaging (CSI) techniques can be applied to follow the formation of hydrogels along chemical gradients. We apply CSI to study the binding of Ca2+ and subsequent gelation of peptide assemblies at alkaline pH. Using metal ion-binding molecules as probes, we are able to detect the presence of bound Ca2+ ions on the surface of the gel fibres. We briefly explore how knowledge of the surface chemical properties of hydrogels could be used to inform their practical application in fields such as drug delivery and environmental remediation

NMR spectroscopy in inorganic chemistry

90 hlm, ; ill, ; 25 cm

Analysis of the mesh size in a supramolecular hydrogel by PFG-NMR spectroscopy

Pulsed field gradient NMR (PFG-NMR) spectroscopy has been used to determine the network mesh size in stable hydrogels formed upon addition of Ca 2+ to solutions of naphthalene diphenylalanine (2FF). At pH 12, the solutions at 0.55 wt% 2FF comprise worm-like micelles. Addition of Ca 2+ results in cross-linking of these micelles. The self-diffusion of dextran guests of nominal 6, 40, 70, 100, 500, 670, 1400 and 2000 kDa, possessing hydrodynamic diameters (2Rh) similar to the expected pore sizes in these systems, was studied both in the precursor micellar solutions and in the hydrogels. The diffusivity of probes with 2Rh < 40 nm is restricted to a similar extent in both types of network with diffusion coefficients scaling as ∼Mr-0.5, where Mr is the nominal mass of the probe, consistent with relatively unrestricted diffusion. Diffusion coefficients fit well the equation Dn/D o = exp(-Rh/ξ), where Dn and Do are the diffusion coefficients in the presence and absence of network respectively and ξ is the mesh size, giving a mesh size of approximately 40 nm. The heaviest ca. 10% of the nominal 2000 kDa dextran fraction having approximate mass and hydrodynamic diameter 3300 kDa and 84 nm respectively was almost immobilised by the gel, consistent with this estimate of the mesh size. The restriction was much weaker in the micellar solution, which is attributed to the transient nature of this micellar network in the absence of Ca 2+. Finally, the mesh size for micellar solutions prepared at 1.1 wt% 2FF is smaller than that of micellar solutions prepared at lower concentrations of 2FF. However, the corresponding gels have a larger mesh size than those prepared at lower concentrations of 2FF. We attribute this to increased fibre aggregation at the higher 2FF concentration. This correlates with lower rheological moduli at higher 2FF concentrations