Solvation of the thiocyanate ion in three different deep eutectic solvents (DES) was investigated by linear FTIR spectroscopy, and Two Dimensional IR spectroscopy. Linear infrared spectroscopy reveals that the thiocyanate ion forms a hydrogen bond through its sulphur atom, while its nitrile end remains free. Photon-echo vibrational spectroscopy shows that the thiocyanate has a frequency-frequency correlation function (FFCF) with two distinct dynamics occurring on the picosecond time scale in all of the studied solvents. The observed dynamics is assigned to in-place and diffusional motions of the components within the thiocyanate solvation shell. Molecular dynamics simulations and ab initio calculations confirm the experimental findings and their molecular interpretation. In addition, theoretical modeling of the thiocyanate nitrile stretch lineshape suggests that alcohol-based DES are more structurally disorganized than the amide-based analogue. However, the organization observed in the different DES is not sufficient to explain physical properties, such as density, indicating that the amount of defects (i.e., hole theory) is not sufficient to fully describe the properties of DES.

Deep eutectic solvents (DES) are a new class of designer solvents with a wide range of possible applications. DESs are typically made from an ionic compound and a hydrogen bond donor, but lately DESs made of nonionic compounds with interesting properties have started to appear. This study focuses on describing the structure, dynamics, and interactions of a nonionic DES composed of N-methylacetamide (NMA) and lauric acid (LA). Linear IR and time-resolved IR experiments show that LA–NMA DES is the result of hydrogen bond interaction between the two molecular components, though the interaction energy is only favored by ∼1 kJ/mol with respect to the pure components. The IR experiments also reveal the presence of molecular heterogeneities produced by the nanosegregation of polar and nonpolar domains formed by N-methylacetamide and lauric acid, respectively. In addition, it is observed that the hydrogen bond interaction between components occurs at the interface of the two distinct polarity domains. The proposed molecular picture is also supported by the observation of nanodomains with the approximate size of two lauric acids via small-angle X-ray scattering.

The liquid structure of five different amide-based deep eutectic solvents (DESs) as a function of the chemical structure of the hydrogen bond acceptor (HBA) was investigated by linear Fourier transform infrared (FTIR) and two-dimensional infrared (2DIR) spectroscopies. Linear FTIR spectroscopy shows that the amide band of the DESs is not significantly affected by the chemical structure and symmetry of the HBA cation. However, its excitonic nature does not allow us to draw further conclusions. Analysis of the C amide line shapes derived from the 2DIR spectra reveals that the different DESs do not show appreciable differences in the level of disorganization. The vibrational dynamics, derived from the photon echo experiments on theC amide, shows that there is a fast component with a time scale of ∼1 ps irrespective of the HBA. The ultrafast dynamics is assigned to hydrogen bond making and breaking between amides. In addition, a slow dynamical component is observed in the time evolution of the photon echo signal. This contribution appears to be correlated with the asymmetry and polarity of the moieties of the HBA. The overall dynamics is rationalized in terms of a microscopic heterogeneous structure of the DESs, where the heterogeneities create domains that slow the hydrogen bond making and breaking. Molecular dynamics simulations provide additional support for our modeling of the data. In addition, the presence of nanoscopic heterogeneities is consistent with the observation of an endortherm at 23 °C in the differential scanning calorimetry thermogram, which evidenced a phase transition at 23 °C, even though the tested DESs have a melting temperature below -40 °C.

Background: In the randomized phase III KEYNOTE-181 study, pembrolizumab prolonged overall survival (OS) compared with chemotherapy as second-line therapy in patients with advanced esophageal cancer and programmed death-ligand 1 (PD-L1) combined positive score (CPS) 10. We report a post hoc subgroup analysis of patients with esophageal squamous cell carcinoma (ESCC) enrolled in KEYNOTE-181 in Asia, including patients from the KEYNOTE-181 China extension study. Patients and methods: Three hundred and forty Asian patients with advanced/metastatic ESCC were enrolled in KEYNOTE-181, including the China cohort. Patients were randomly assigned 1 : 1 to receive pembrolizumab 200 mg every 3 weeks for 2 years or investigator's choice of paclitaxel, docetaxel, or irinotecan. OS, progression-free survival, response, and safety were analyzed without formal comparisons. OS was evaluated based on PD-L1 CPS expression level. Results: In Asian patients with ESCC, median OS was 10.0 months with pembrolizumab and 6.5 months with chemotherapy [hazard ratio (HR), 0.63; 95% CI 0.50-0.80; nominal P < 0.0001]. Median progression-free survival was 2.3 months with pembrolizumab and 3.1 months with chemotherapy (HR, 0.79; 95% CI 0.63-0.99; nominal P ¼ 0.020). Objective response rate was 17.1% with pembrolizumab and 7.1% with chemotherapy; median duration of response was 10.5 months and 7.7 months, respectively. In patients with PD-L1 CPS <1 tumors (pembrolizumab versus chemotherapy), the HR was 0.99 (95% CI 0.56-1.72); the HR (95% CI) for death was better for patients with PD-L1 CPS cut-offs >1 [CPS 1, 0.57 (0.44-0.75); CPS 5, 0.56 (0.41-0.76); CPS 10, 0.53 (0.37-0.75)]. Treatmentrelated adverse events were reported in 71.8% of patients in the pembrolizumab group and 89.8% in the chemotherapy group; grade 3-5 events were reported in 20.0% and 44.6%, respectively. Conclusions: Pembrolizumab monotherapy demonstrated promising efficacy in Asian patients with ESCC, with fewer treatment-related adverse events than chemotherapy. PD-L1 CPS 1 is an appropriate cut-off and a predictive marker of pembrolizumab efficacy in Asian patients with ESCC.

A new deep eutectic solvent (DES) was developed as a phase-selective gelator for oil-spill remediation. The newly designed nonionic DES is based on a combination of an amide (N-methylacetamide) and a long chain carboxylic acid (lauric acid) and does not require any synthetic procedure besides mixing. Our studies show that the DES works as gelator by forming a gel between lauric acid and the hydrocarbon, whereas the amide serves to form the DES and dissolves in water during the gelation process. In addition, the DES material has gelation properties comparable to those considered as state-of-the-art. Overall, the newly developed material shows a promising future in oil recovery methodologies.