The gas-phase adsorption of 11-mercaptoundecanoic acid (HOOC(CH2)10SH) on Ni(111) in ultrahigh vacuum was studied using angle-dependent X-ray photoelectron spectroscopy (ADXPS) and temperature-programmed desorption (TPD). We present evidence which shows that 11-mercaptoundecanoic acid is adsorbed to Ni(111) via the sulfur atom with the carboxylic acid group disposed away from the surface. The monolayer thickness of this molecule, 10.4 ± 1.7 Å, estimated by photoelectron attenuation in ADXPS, was comparable to ellipsometric measurements of related n-alkanethiols on Au(111). The interaction of polar (CH3OH) and nonpolar (n-C6H14) probe molecules with this acid-terminated surface showed that the former interact more strongly than the latter as studied by TPD. A Redhead analysis was used to analyze the TPD spectra of CH3OH and n-C6H14 desorbing from this thiol-covered, acid-terminated Ni(111) surface. The calculated low-coverage desorption energy for CH3OH desorption from HOOC(CH2)10SH/Ni(111) was 41 kJ mol-1. The calculated low-coverage desorption energy for n-C6H14 desorption from HOOC(CH2)10SH/Ni(111) was 37 kJ mol-1.

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The interactions of vapor-deposited methanol, ethanol, 1-propanol, and 1-hexanol with an 11-mercaptoundecanoic acid (HOOC(CH2)10SH) self-assembled monolayer adsorbed on a nickel(111) single crystal were studied in ultrahigh vacuum by temperature-programmed desorption (TPD) and X-ray photoelectron spectroscopy (XPS). The peak shapes of the TPD spectra for methanol, ethanol, and propanol desorption are similar, suggesting that these alcohols undergo similar desorption processes. Their peak desorption temperatures at the lowest submonolayer fluences increased with the number of carbons in the alcohol, suggesting that the methyl and methylene groups, as well as the hydroxyl group, participate in the adsorbed alcohol monolayer's interactions at the acid-terminated self-assembled monolayer surface. Threshold TPD (TTPD) was used for a quantitative analysis of the desorption spectra as a function of coverage. The structure and behavior of hexanol's desorption spectra suggest a different desorption process than its lower-molecular-weight analogues. Of all the alcohols studied, hexanol exhibited the strongest interaction with the acid-terminated surface. The desorption energies calculated by the TTPD method for the straight-chain n-alcohols C1−C3 (15−20 kJ mol-1) and C6 (∼38 kJ mol-1) in the submonolayer regime were in the range expected (10−40 kJ mol-1) for hydrogen bonding.

The low limits of detection afforded by second harmonic generation (SHG) microscopy coupled with image analysis algorithms enabled quantitative modeling of the temperature-dependent crystallization of active pharmaceutical ingredients (APIs) within amorphous solid dispersions (ASDs). ASDs, in which an API is maintained in an amorphous state within a polymer matrix, are finding increasing use to address solubility limitations of small-molecule APIs. Extensive stability testing is typically performed for ASD characterization, the time frame for which is often dictated by the earliest detectable onset of crystal formation. Here a study of accelerated stability testing on ritonavir, a human immunodeficiency virus (HIV) protease inhibitor, has been conducted. Under the condition for accelerated stability testing at 50 °C/75%RH and 40 °C/75%RH, ritonavir crystallization kinetics from amorphous solid dispersions were monitored by SHG microscopy. SHG microscopy coupled by image analysis yielded limits of detection for ritonavir crystals as low as 10 ppm, which is about 2 orders of magnitude lower than other methods currently available for crystallinity detection in ASDs. The four decade dynamic range of SHG microscopy enabled quantitative modeling with an established (JMAK) kinetic model. From the SHG images, nucleation and crystal growth rates were independently determined.

Single-particle tracking of crystal growth performed in situ enables substantial improvements in the signal-to-noise ratio (SNR) for recovered crystal nucleation and growth rates by nonlinear optical microscopy. Second harmonic generation (SHG) is exquisitely sensitive to noncentrosymmetric crystals, including those produced by many homochiral active pharmaceutical ingredients (APIs). Accelerated stability testing at elevated temperatures and relative humidity informs design of pharmaceutical formulations. In the present work, we demonstrate reduction in the Poisson noise associated with the finite number of particles present in a given field of view through continuous monitoring during stability testing. Single-particle tracking enables recovery of crystal growth rates of individual crystallites and enables unambiguous direct detection of nucleation events. Collectively, these capabilities provide significant improvements in the signal-to-noise for nucleation and crystal growth measurements, corresponding to approximately an order of magnitude reduction in anticipated measurement time for recovery of kinetics parameters.