Decisive Role of Hydrophobicity on the Effect of Alkylammonium Chlorides on Protein Stability: A Terahertz Spectroscopic Finding Debasish Das Mahanta, Nirnay Samanta, and Rajib Kumar Mitra* Chemical, Biological and Macromolecular Sciences, S. N. Bose National Centre for Basic Sciences Block-JD, Sector-III, Salt Lake, Kolkata, 700106, India * S Supporting Information ABSTRACT: Many biologically important processes involve a subtle interplay between Columbic and hydrophobic interactions among molecular groups with water. A comprehensive under- standing of such processes, specially while occurring simultaneously in the same molecule is of practical importance. In this contribution, we report the ultrafast (subpicosecond to pico- second) collective hydrogen bond dynamics of water in the extended hydration layers in a series of alkylammonium chloride salts using THz time domain spectroscopic (TTDS) technique (0.3-1.6 THz (10-55 cm -1 )). We found the THz absorption coefficient (α) of the salt solutions systematically vary with the salt type. We obtain the hydrogen bond relaxation dynamics by fitting the frequency dependent dielectric constants in a multiple Debye dielectric relaxation model. We found these salts to transform from being a water “structure breaker” to “structure maker” with increasing carbon content. We also investigate their effect on a model protein “bovine serum albumin” and found a systematic trend toward disrupting the protein secondary structure. The associated changes in the protein hydration in the presence of these salts have also been investigated using TTDS. ■ INTRODUCTION Nonpolar hydrophobic molecules in water are believed to increase disorder due to their inability to form a H-bond with the polar water molecules. 1 However, they can also enhance the ordering in their surrounding water network. 2 The notion of hydrophobic hydration, still a popular topic of research, is highly specific on the solute type and dimension. Either small hydrophobic solutes get arrested within the polyhedral cage formed by the under- or uncoordinated water molecules with dangling O-H bonds 2,3 or the solutes as well as the solvent separately aggregate to form clusters 4 with an enhanced H- bond network. Larger solutes can even disrupt the tetrahedral network of water. In both cases, there exist defects in the water H-bonded network, 3 which is the key driving factor that governs most of the physicochemical and biological pro- cesses. 5-9 Likewise, ion-water interaction also plays important role in biology and chemistry. 10,11 Electrolytes perturb the H- bonded structure in liquid water, thereby either strengthen- ing 12,13 or rupturing the water network, 12,14 the extent being highly ion specific in nature. 15-17 Bakker et al. have shown that hydration dynamics of ions is cooperative in nature and depends on the hydration of the counterions also. 18 THz spectroscopic investigation by Havenith et al. 19,20 established a strong correlation between hydration dynamics and the “rattling” motion of metal ions. A direct correlation between H-bonding and water structure making/breaking ability of ions is highly debatable. Strongly hydrated ions tend to align the static dipoles of their surrounding water molecules. Such effect could be extended beyond the second or third solvation shell of the ions. 12,21 Structural information on ion hydration has so far been realized using neutron and X-ray diffraction, 22 X-ray absorption spectroscopy, 23 IR and Raman spectroscopy 24 while the corresponding dynamics has been revealed using various techniques including fs IR pump-probe spectroscopy, 18,25 broadband dielectric spectroscopy, 26,27 2D IR vibrational echo experiments, 28,29 optical Kerr rotation spectroscopy 30 vibra- tional sum frequency generation spectroscopy 31,32 and various computer simulation studies. 13,33,34 Instead of understanding electrostatic and hydrophobic interactions individually, it is of practical importance to study them while operating simultaneously. In this regard, cations consisting of water repelling moieties have recently attracted attention among researchers owing to their unique hydration behavior. 32, 35-39 Alkylammonium halides are the most extensively studied salts that possess the rare combination of ionic and hydrophobic characters in the same molecule, with a tunable hydrophobicity. Such molecules contain short chain alkanes and unlike amphiphilic molecules do not usually aggregate at moderate concentrations. 36 There have been several studies about the physical nature of water around these molecules using various experimental and simulation techni- ques. 37,40-44 These studies have questioned the popular belief Received: May 1, 2017 Revised: July 24, 2017 Published: July 25, 2017 Article pubs.acs.org/JPCB © XXXX American Chemical Society A DOI: 10.1021/acs.jpcb.7b04088 J. Phys. Chem. B XXXX, XXX, XXX-XXX