Quantitative NMR (qNMR) for pharmaceutical analysis: The pioneering work of George Hanna at the US FDA

In the last two decades, quantitative NMR (qNMR) has become increasingly important for the analysis of pharmaceuticals, chemicals, and natural products including dietary supplements. For the purpose of quality control and chemical standardization of a large variety of pharmaceutical, chemical, and medicinal products, qNMR has proven to be a valuable orthogonal quantification method and a compelling alternative to chromatographic techniques. This work reviews a fundamental component of the early development of qNMR, reflected in the pioneering work of the late George M. Hanna during the years between 1984 and 2006 at the US Food and Drug Administration (FDA). Because Hanna performed the majority of his groundbreaking work on a 90‐MHz instrument, his legacy output connects with recent progress in low‐field benchtop NMR instrumentation. Hanna gradually established the utility of qNMR for the routine quality control analyses practiced in pharmaceutical and related operations well ahead of his peers. His work has the potential to inspire new developments in qNMR applied to small molecules of biomedical importance.     

The effect of external forces on the initial dissociation of RDX (1,3,5‐trinitro‐1,3,5‐triazine): A mechanochemical study

Experimental and theoretical studies have proposed different initiation reactions for the decomposition of hexahydro‐1,3,5‐trinitro‐1,3,5‐triazine (RDX). Three primary reactions are considered to start RDX decomposition: homolytic N? N bond fission, HONO elimination, and concerted fission of C? N bonds. The focus of this article is to study the effect of external forces on the energy barrier and reaction energies of all three mechanisms. We used the Nudged Elastic Band method along with ab initio Density Functional Theory within the framework of a generalized force‐modified potential energy surface (G‐FMPES) to calculate the minimum energy paths at different compressive (corresponding to pressure between approximately 6 and 294 MPa) and expansive force values (between 10 and 264 pN). For all three reactions, the application of an expansive force increases the exothermicity and lowers the energy barriers to different extents, while a compressive force decreases the exothermicity and raises the energy barrier to different extents.     

In situ PM‐IRRAS studies of organothiols and organosilane monolayers–ZnO interfaces at high water activities

In situ photoelastic‐modulated Fourier transform infrared reflection absorption spectroscopy has been applied for the investigation of interfacial stability of organothiol and organosilane monolayer films on nanocrystalline zinc oxide thin films. It has been shown that for octadecyltriethoxysilane films, exposure to high water activities results in physisorption of water in the cross‐linked film. This high water activity at the interface leads to a reversible wet de‐adhesion of the interfacial silanol groups from the ZnO surface. However, the organothiol seems to form a denser monolayer and a stable by S–Zn bond that is resistant to the competition with adsorbed water. The reversible attachment for cross‐linked organosilanol films has been demonstrated for the first time by means of an in situ spectroscopic method on model ZnO surfaces. Copyright © 2016 John Wiley & Sons, Ltd.     

Thermodynamics of alcohols and monosaccharides in aqueous solutions of thiourea at 25°C

The excess enthalpies of twelve ternary aqueous solutions of alcohols or monosaccharides containing thiourea have been determined by flow microcalorimetry at 25°C. The coefficients of the virial expansion of the excess enthalpies are compared with those reported in the literature for the same ternary solutions containing urea in place of thiourea. The cross-interaction coefficients are positive for the thiourea-alcohol systems and depend on the length and branching of the alkyl chain of the alcohols. On the other hand, they are negative for the thiourea-monosaccharide systems. Thus, thiourea, as urea, can be used as a probe to reveal differences in the behavior of families of solutes characterized by the same functional groups. The results can be interpreted in terms of the relative stabilities of hydration cospheres of hydrophobic or hydrophilic solutes toward a chaotropic agent such as thiourea.Presented at the sixth Italian meeting on Calorimetry and Thermal Analysis (AICAT) held in Naples, December 4–7, 1984.     

Partial least-squares modelling of dye fastness to light

Several physicochemical properties (¹³C-n.m.r., spectrophotometric, chromatographic, calorimetric) were measured for a series of 38 azo dyes in order to test the existence of relationships between one or more of these data sets and the fastness of the dyes on polyester fabric. The partial least-squares method was applied; it had previously proved useful in establishing structure/property relationships for the same dyes. It is shown that ¹³C-n.m.r. data can be used successfully to predict dye fastness to light. These data are quickly and cheaply obtained with small amounts of compound.     

Synthesis of pyrazolo[4,5-d]- and pyrazolo[4,5-c][1]benzazepine derivatives. IV

Following our reports on synthetic tricyclic analogues of antitumor anthramycin the synthesis of some isomers pyrazolo[4,5-d]- and pyrazolo[4,5-c][1]benzazepine derivatives is reported.     

Quantitative surface analysis performed with an imaging photoelectron spectrometer

The paper gives an outline of the basic principle of our imaging technique for XPS. The advantage of the concept is its excellent applicability to quantitative pixel information. This idea is verified by two examples which are representative for routine problems in XPS. These are quantitative surface analysis and determination of overlayer thicknesses. A lateral resolution of at least 0.2 mm is achieved and thus a pixel size of 0.2 mm × 0.2 mm can be quantified automatically by means of numerical algorithms without need of reference samples.Dedicated to Professor Günther Tölg on the occasion of his 60th birthday     

Catenation and Aggregation of Multi‐Cavity Coordination Cages

A series of metal‐mediated cages, having multiple cavities, was synthesized from Pd^II cations and tris‐ or tetrakis‐monodentate bridging ligands and characterized by NMR spectroscopy, mass spectrometry, and X‐ray methods. The peanut‐shaped [Pd₃L¹₄] cage deriving from the tris‐monodentate ligand L¹ could be quantitatively converted into its interpenetrated [5Cl@Pd₆L¹₈] dimer featuring a linear {[Pd‐Cl‐]₅Pd} stack as an unprecedented structural motif upon addition of chloride anions. Small‐angle neutron scattering (SANS) experiments showed that the cigar‐shaped assembly with a length of 3.7 nm aggregates into mono‐layered discs of 14 nm diameter via solvophobic interactions between the hexyl sidechains. The hepta‐cationic [5Cl@Pd₆L¹₈] cage was found to interact with polyanionic oligonucleotide double‐strands under dissolution of the aggregates in water, rendering the compound class interesting for applications based on non‐covalent DNA binding.