David Edward Budil

MnSb is a metallic ferromagnet with a high Curie temperature (∼587 K) and strong spin–orbit coupling, making it attractive for room-temperature spintronic and magnetic sensing applications. We report heteroepitaxial growth of MnSb on GaAs (111) by molecular beam epitaxy, yielding locally epitaxial, strain-relaxed island structures with multiple dominant crystallographic orientations. Structural analysis reveals the coexistence of basal-plane- and pyramidal-plane-oriented domains, enabling investigation of magneto-crystalline anisotropy in an orientationally inhomogeneous ferromagnetic system. Room-temperature magnetic characterization using magnetic force microscopy, scanning nitrogen-vacancy center magnetometry, and angle-dependent ferromagnetic resonance demonstrates a strongly anisotropic, orientation-dependent magnetic response across multiple length scales. Correlating these magnetic responses with crystal structure and local stray fields reveals the role of structural inhomogeneity in governing magnetic anisotropy and spin dynamics in MnSb thin film. These results establish MnSb thin films as a promising platform for vector magnetic-field sensing and orientation-encoded spintronic device concepts.

Objectives: The effect of 2-hydroxpropyl-β-cyclodextrin (2HPβCD) with or without divalent metal ions (Ca²⁺, Mg²⁺, and Zn²⁺) on the stability of dalbavancin in acetate buffer was investigated. Methods: Dalbavancin recovery from formulations with 2HPβCD and divalent metal ions after four weeks of storage at 5 °C and 55 °C was measured by RP-HPLC and HP-SEC; a longer-term study was carried out over six months at 5 °C, 25 °C, and 40 °C. Binding of 2HPβCD was characterized by isothermal titration calorimetry (ITC) and nuclear magnetic resonance (NMR). Results: The stability of the dalbavancin formulations after 4 weeks at 55 °C in 10 mM acetate buffer was significantly improved with 0.6 mM, 5.5 mM, and 55 mM 2HPβCD relative to without 2HPβCD. No further improvement was observed with the addition of any of the divalent cations. Dalbavancin in a 1:10 molar ratio with 2HPβCD was more stable at a concentration of 1 mg/mL than at 20 mg/mL under accelerated conditions at 40 °C for six months. ITC revealed two 2HPβCD binding sites to dalbavancin in 10 mM acetate: one with a 1:1 stoichiometry and thermodynamics consistent with known cyclodextrin–drug interactions, and a second with 0.1:1 stoichiometry, a positive binding enthalpy, and an unusually large entropy of binding. NMR spectroscopy indicates that dalbavancin exhibits aggregation in acetate buffer that is disrupted by 2HPβCD binding. Conclusions: 2HPβCD significantly improves the short- and long-term heat stability of dalbavancin in pH 4.5 acetate buffer at and above molar ratios of 1:1. The strong 1:1 binding of 2HPβCD to dalbavancin demonstrated by ITC confirms that this stability is conferred by the formation of a stable complex. This observation, combined with the NMR results, points to the aliphatic hydrocarbon chain of the glycone moiety as the most likely site of 2HPβCD–dalbavancin interaction.

Heisenberg spin exchange between nitroxide (Tempone) spin probes has been measured as a function of concentration in the aqueous phase of the hydrated ion exchange membrane Nafion 117. The observed fast-motional electron paramagnetic resonance spectra were analyzed in terms of the stochastic Liouville equation lineshape calculation of Freed and coworkers and the “new paradigm” for interpreting spin exchange effects proposed by Salikhov. Differences between the effective spin exchange measured from the spectrum by these methods are presented and compared, and indicate that dipolar interactions make a significant contribution to spin exchange in this system. In acidic Nafion membranes, the spin probes are deactivated over time, allowing simultaneous measurement of the decay kinetics and spin exchange as a function of paramagnetic probe concentration. Both these processes deviate from the behavior that would be expected from classical chemical kinetics in isotropic media. The results are discussed in terms of currently available models for diffusion and reaction in a percolation network.

Purpose The effect of monovalent (Na⁺ and K⁺) and divalent (Ca²⁺, Mg²⁺, and Zn²⁺) metal ions combined with citrate or acetate buffers (pH 4.5) on the stability of dalbavancin in aqueous solutions was investigated. Method RP-HPLC and HP-SEC were used to evaluate the stability of aqueous solutions of dalbavancin in different combinations of buffers and metal ions after four weeks of storage at 5°C and 55°C. A long-term study of formulations with divalent metal ions was conducted over six months at 5°C., 25°C and 40°C using RP-HPLC. Results All formulations in citrate buffered solutions precipitated. Dalbavancin solutions in 10 mM acetate buffer at 55°C were more stable in 10 mM CaCl₂, 5 mM ZnCl₂ and 10 mM MgCl₂ than those containing 2 mM NaCl or 5 mM KCl, although the MgCl₂ formulations precipitated slightly. No significant effect was observed for any of the divalent metal ions at 40°C for six months. Conclusion Dalbavancin’s stability in solution was improved by a combination of acetate and divalent metal ions at 55°C for four weeks. No effect was observed with acetate or metal ions alone, and no effect was observed after six months at 40°C suggesting that acetate and divalent metal ions together interact with dalbavancin via a thermally activated step to inhibit hydrolysis of the drug.

Historically, the primary result of an EPR experiment is the CW EPR spectrum, typically displayed as the first derivative of the absorption spectrum as a function of the magnetic field. Beyond very qualitative assessments, the detailed analysis of an experimental EPR spectrum is a difficult inverse problem. Given a set of parameters and a model, it is easy to calculate a spectrum, but given an EPR spectrum, it is a challenge to decide on the correct model and find all defining parameters of interest. Programs to simulate and fit CW EPR spectra have been around for a long time. Except for a very well-defined model system, an experimental spectrum of a spin labeled protein is typically a mix of multiple states. This article focuses on the analysis of the CW spectrum in several stages of detail, from qualitative to detailed. The use of the EPR lineshape fitting program MultiComponent developed in the Hubbell lab is used to illustrate common approaches to extract information relevant to protein structure, function, dynamics, and thermodynamics.

Heisenberg spin exchange (HSE) between nitroxide (Tempone) spin probes has been measured as a function of concentration in the aqueous phase of the hydrated ion exchange membrane Nafion 117. The observed fast-motional electron paramagnetic resonance spectra were analyzed in terms of the perturbation expressions given by Bales and Peric based on the earlier monograph of Molin et al., as well as by the full stochastic Liouville equation lineshape calculation of Freed and coworkers. Differences between the methods for determining HSE from the spectrum are presented and discussed. In acidic Nafion membranes, the spin probes are deactivated over time, allowing simultaneous measurement of the decay kinetics and HSE as a function of paramagnetic probe concentration. Both processes deviate from the behavior that would be expected based on classical diffusion and chemical kinetics in isotropic media. The results are discussed in terms of currently available models for diffusion and reaction in a percolation network.

Purpose New formulations of the glycopeptide drug dalbavancin containing 2-hydroxpropyl-β-cyclodextrin (2HPβCD) with or without divalent metal ions in phosphate buffer (pH 7.0) were tested to evaluate whether these excipients influence the aqueous solution stability of dalbavancin. Method Recovery of dalbavancin from phosphate buffered solutions at pH 7.0 with different concentrations of 2HPβCD and a divalent metal ion (Ca²⁺, Mg²⁺, or Zn²⁺) was evaluated by RP-HPLC and HP-SEC after four weeks of storage at 5°C and 55°C. A long-term study of formulations with 2HPβCD and Mg²⁺ was carried out over six months at 5°C, 25°C, and 40°C using RP-HPLC. Results Dalbavancin solutions with either 5.5 mM or 55 mM 2HPβCD were significantly more stable with Mg²⁺ than with the other divalent metal ions, both at 55°C for four weeks and at 40°C for six months. Dalbavancin was found to be more stable in aqueous solutions at a concentration of 1 mg/mL than at 20 mg/mL with 2HPβCD and Mg²⁺ at 40°C for six months. Conclusion The results suggest that 2HPβCD forms an inclusion complex with dalbavancin that slows the formation of the major degradant, mannosyl aglycone (MAG). The effect of 2HPβCD is increased in the presence of Mg²⁺ and phosphate at pH 7.0, and the complex is more stable at a dalbavancin concentration of 1 mg/mL than at 20 mg/mL. These observations point towards the possibility of formulating a dalbavancin injection solution with a long shelf life at room temperature and physiological pH.

Heat stress studies have been conducted in support of developing a heat-stable liquid solution of dalbavancin. The degradation products that form in heat-stressed buffered dalbavancin solutions have been identified, including the known major degradation product, mannosyl aglycone (MAG), and four previously uncharacterized compounds. Liquid chromatography-mass spectrometry/mass spectrometry (LC–MS/MS) was used to identify the degradation products of dalbavancin in acetate- and phosphate-buffered solutions under thermal stress at 70 °C and the changes in the degradation pattern in the presence of 2HPβCD and divalent metal ions. Although Ca²⁺, Mg²⁺, and Zn²⁺ did not reduce dalbavancin degradation under thermal stress in acetate buffer, 2HPβCD significantly reduced its overall degradation, in particular, the formation of MAG. This protective effect was enhanced by the addition of Ca²⁺ to the formulation. In phosphate buffer, MAG formation was also reduced by the addition of 2HPβCD, although significant increases in other degradation products were observed in this case. The addition of Mg²⁺ to 2HPβCD significantly reduced the overall degradation while increasing MAG formation somewhat. The results strongly suggest that 2HPβCD forms a complex with the hydrophobic glycone tail of dalbavancin, suppressing hydrolysis of the glycosidic bond.

Glycopeptide antimicrobials are a class of naturally occurring or semi-synthetic glycosylated products that have shown antibacterial activity against gram-positive organisms by inhibiting cell-wall synthesis. In most cases, these drugs are prepared in dry powder (lyophilized) form due to chemical and physical instability in aqueous solution; however, from an economic and practical point of view, liquid formulations are preferred. Researchers have recently found ways to formulate some glycopeptide antibiotic therapeutic drugs in aqueous solution at refrigerated or room temperature. Chemical degradation can be significantly slowed by formulating them at a defined pH with specific buffers, avoiding oxygen reactive species, and minimizing solvent exposure. Sugars, amino acids, polyols, and surfactants can reduce physical degradation by restricting glycopeptide mobility and reducing solvent interaction. This review focuses on recent studies on glycopeptide antibiotic drug stability in aqueous solution. It is organized into three sections: (i) glycopeptide antibiotic instability due to chemical and physical degradation, (ii) strategies to improve glycopeptide antibiotic stability in aqueous solution, and (iii) a survey of glycopeptide antibiotic drugs currently available in the market and their stability based on published literature and patents. Antimicrobial resistance deaths are expected to increase by 2050, making heat-stable glycopeptides in aqueous solution an important treatment option for multidrug-resistant and extensively drug-resistant pathogens. In conclusion, it should be possible to formulate heat stable glycopeptide drugs in aqueous solution by understanding the degradation mechanisms of this class of therapeutic drugs in greater detail, making them easily accessible to developing countries with a lack of cold chains.

Phase change materials help realize voltage tunable spin dynamics.