Experimental two-dimensional infrared spectra of methyl thiocyanate in water and organic solvents.

Thiocyanates, nitriles, and azides represent a versatile set of vibrational probes to measure the structure and dynamics in biological systems. The probes are minimally perturbative, the nitrile stretching mode appears in an otherwise uncongested spectral region, and the spectra report on the local environment around the probe. Nitrile frequencies and lineshapes, however, are difficult to interpret, and theoretical models that connect local environments with vibrational frequencies are often necessary. However, the development of both more accurate and intuitive models remains a challenge for the community. The present work provides an experimentally consistent collection of experimental measurements, including IR absorption and ultrafast two-dimensional infrared (2D IR) spectra, to serve as a benchmark in the development of future models. Specifically, we catalog spectra of the nitrile stretching mode of methyl thiocyanate (MeSCN) in fourteen different solvents, including non-polar, polar, and protic solvents. Absorption spectra indicate that π-interactions may be responsible for the line shape differences observed between aromatic and aliphatic alcohols. We also demonstrate that a recent Kamlet-Taft formulation describes the center frequency MeSCN. Furthermore, we report cryogenic infrared spectra that may lead to insights into the peak asymmetry in aprotic solvents. 2D IR spectra measured in protic solvents serve to connect hydrogen bonding with static inhomogeneity. We expect that these insights, along with the publicly available dataset, will be useful to continue advancing future models capable of quantitatively describing the relation between local environments, line shapes, and dynamics in nitrile probes.

BoxCARS 2D IR spectroscopy with pulse shaping.

BoxCARS and pump-probe geometries are common implementations of two-dimensional infrared (2D IR) spectroscopy. BoxCARS is background-free, generally offering greater signal-to-noise ratio, which enables measuring weak vibrational echo signals. Pulse shapers have been implemented in the pump-probe geometry to accelerate data collection and suppress scatter and other unwanted signals by precise control of the pump-pulse delay and carrier phase. Here, we introduce a 2D-IR optical setup in the BoxCARS geometry that implements a pulse shaper for rapid acquisition of background-free 2D IR spectra. We show a signal-to-noise improvement using this new fast-scan BoxCARS setup versus the pump-probe geometry within the same configuration.

Origin of thiocyanate spectral shifts in water and organic solvents.

Vibrational spectroscopy is a useful technique for probing chemical environments. The development of models that can reproduce the spectra of nitriles and azides is valuable because these probes are uniquely suited for investigating complex systems. Empirical vibrational spectroscopic maps are commonly employed to obtain the instantaneous vibrational frequencies during molecular dynamics simulations but often fail to adequately describe the behavior of these probes, especially in its transferability to a diverse range of environments. In this paper, we demonstrate several reasons for the difficulty in constructing a general-purpose vibrational map for methyl thiocyanate (MeSCN), a model for cyanylated biological probes. In particular, we found that electrostatics alone are not a sufficient metric to categorize the environments of different solvents, and the dominant features in intermolecular interactions in the energy landscape vary from solvent to solvent. Consequently, common vibrational mapping schemes do not cover all essential interaction terms adequately, especially in the treatment of van der Waals interactions. Quantum vibrational perturbation (QVP) theory, along with a combined quantum mechanical and molecular mechanical potential for solute-solvent interactions, is an alternative and efficient modeling technique, which is compared in this paper, to yield spectroscopic results in good agreement with experimental FTIR. QVP has been used to analyze the computational data, revealing the shortcomings of the vibrational maps for MeSCN in different solvents. The results indicate that insights from QVP analysis can be used to enhance the transferability of vibrational maps in future studies.

MANUSCRIPT Local Crowd, Local Probe: Strengths and Drawbacks of Azidohomoalanine as a Site-Specific Crowding Probe.

Every residue on a protein can be characterized by its interaction with water, in lack or in excess, as water is the matrix of biological systems. Infrared spectroscopy and the implementation of local azidohomoalanine (AHA) probes allow us to move beyond an ensemble or surface-driven conceptualization of water behavior and toward a granular, site-specific picture. In this paper, we examined the role of crowding in modulating both global and local behavior on the ß-hairpin, TrpZip2 using a combination of Fourier-transform infrared spectroscopy (FTIR) spectroscopy, two-dimensional infrared (2D IR) spectroscopy, and molecular dynamics simulations. We found that, at the amino acid level, crowding drove dehydration of both sheet and turn peptide sites as well as free AHA. However, the subpicosecond dynamics showed highly individualized responses based on the local environment. Interestingly, while steady-state FTIR measurements revealed similar responses at the amino-acid level to hard versus soft crowding (dehydration), we found that PEG and glucose had opposite stabilizing and destabilizing effects on the protein secondary structure, emphasizing an important distinction in understanding the impact of crowding on protein structure as well as the role of crowding across length scales.

Forced Interactions: Ionic Polymers at Charged Surfactant Interfaces.

Characterizing electrostatic interactions at heterogeneous interfaces is critical for developing a fundamental description of the dynamic processes at charged interfaces. Water-in-oil reverse micelles (RMs) offer a high degree of tunability across composition, polarity, and temperature, making them ideal systems for studying interactions at heterogeneous liquid-liquid interfaces. In the present study, we use a combination of ultrafast two-dimensional infrared spectroscopy and molecular dynamics (MD) simulations to determine the picosecond interfacial dynamics in RMs containing binary compositions of sorbitan monostearate and anionic or cationic cosurfactants, which are used to tune the ratio of charged to nonionic surfactants at the interface. The positively charged polyethylenimine (PEI) polymer is encapsulated within the RMs, and the carbonyl stretching mode of sorbitan monostearate reports on the interfacial hydrogen-bond populations and dynamics. The results show that hydrogen-bond populations are altered through the inclusion of both negatively and positively charged cosurfactants. Charged surfactants increase interfacial water penetration into the surfactant layer, and the surface localization of polymers decreases water penetration. Local hydrogen-bond dynamics undergo a slowdown with the inclusion of charged surfactants, and the encapsulation of polymers results in similar effects, irrespective of the charge.