2-Naphthalenethiol is a slightly water soluble, white to tan colored solid with a sulfurous, mushroom-like odor. This product provides a sulfurous, meaty, and egg-like taste with a slight nutty nuance to meats, soups, gravies, and many other food applications. 2-Naphthalenethiol has the CAS number 91-60-1.

HPLC-UV/Vis Method Using Chemical Derivatization with 2-Naphthalenethiol

Sulforaphane (SFN) is a naturally occurring sulfur-containing isothiocyanate enriched in natural products, such as broccoli, brussels sprouts, cauliflower, or cabbage. SFN has received significant attention because of its ability to suppress cancer development or metastasis in multiple tissues through different mechanisms. Accordingly, downstream studies for assessing the pharmacokinetics (PK) and pharmacodynamics (PD) profiles of SFN are required for both preclinical and clinical stages of the drug discovery process. Of different derivatizing reagents, such as Cys-ME, mercaptoethanol, benzenethiol, or 2-naphthalenethiol (2-NT), 2-naphthalenethiol (2-NT) exhibits high molar absorptivity and longer and/or specific wavelengths (≥230 nm; 234, 280, and 320 nm), and sensitive detection with reduced interference from the sample matrix can be achieved in comparison to others. Despite such benefits, no studies have employed 2-NT as a derivatizing reagent for SFN quantification measured by the HPLC-UV/Vis method. In the present study, therefore, we utilized the chemical derivatization reaction using 2-naphthalenethiol (2-NT) to improve the detectability of SFN, followed by the development of specific HPLC-UV/Vis analytical conditions and justified each validation characteristic within acceptable limits. Moreover, we successfully applied the proposed method to study rat pharmacokinetics (PK) following oral administration of SFN.[1]

The derivatization process of SFN or its internal standard (IS) isothiocynate using 2-NT is shown. The derivatization condition was optimized by changing various parameters, i.e., the concentration of the derivatization agent 2-Naphthalenethiol (0.05–0.5 M), range of pH (4.0–10.0), incubation temperature (25 to 60 °C), and period of incubation (10–180 min). As such, the optimal derivatization conditions were obtained with 0.3 M of 2-NT in acetonitrile with phosphate buffer (pH 7.4) by incubation for 60 min at 37 °C. While prior studies established the HPLC-UV/Vis methods without chemical derivatization, which exhibited that UV absorbance at a short wavelength (202–210 nm) causes a relatively high background and low sensitivity, the use of 2-Naphthalenethiol derivatization significantly increases the UV absorption at a wavelength of 234 nm, helping to improve the detectability of SFN. Moreover, the advantage of this method lies in its low limit of detection (LOD) of 0.0078 μg/mL compared to a previous HPLC assay with an LOD of 0.01 μg/mL. The assay was fully validated, with good selectivity and linearity over a large range of 0.01–2.0 μg/mL. SFN was stable in the solvent employed in this study and plasma for at least 6 months and 1 month, respectively.

Electrochemical Characterization of 2-Naphthalenethiol Self-Assembled Monolayers

Self-assembled monolayer (SAM) refers to a single layer of molecules on a substrate, which are adsorbed spontaneously by chemisorption and exhibit a high degree of orientation, molecular ordering, and packing density.  They have received a great deal of attention in recent times because of their potential application in a variety of fields, such as sensors,  photolithography, nonlinear optical materials, high-density memory storage devices,  and corrosion protection. Whitesides et al. investigated the metal?insulator?metal junction based on the SAM of 2-naphthalenethiol on Au and Ag by measuring the breakdown voltage and found that the SAM on the Au junction is mechanically stable but immediately breaks down on application of potential.  To the best of our knowledge, there is no report in the literature on the monolayer formation and characterization of naphthalenethiol on gold, except by Randall and Joseph.  These authors reported the formation of SAMs of 2-naphthalenethiol and bis(2-naphthyl) disulfide onto bulk gold using liquid chromatography and diode array spectroscopy and showed that the naphthalene ring is tilted to the Au surface normal. There is, however, no report on the electrochemical characterization, determination of surface coverage based on pinhole defect analysis, study on kinetics of SAM formation, or structural arrangement of SAMs of 2-naphthalenethiol on Au.[2]

STM studies have been used to characterize the structure of the monolayer at the molecular level and also to understand the nature of the adsorbed film. Figure 11a shows the constant current STM image of the bare gold surface, which was used to form the monolayer film at a 6 × 6 nm range. Though the atomic features could not be resolved, the surface has a predominantly Au(111) orientation, as determined by X-ray diffraction studies. Figure 11b shows the Fourier filtered constant height images of the 2-naphthalenethiol monolayer adsorbed on the evaporated gold surface at a 6 × 6 nm range. The chemisorbed S?S bond distance is determined to be 5 ? in the adjacent columns of the image. The vertical bright spots correspond to the individual molecules of 2-naphthalenethiol adsorbed on Au. The possible structure of 2-naphthalenethiol orientations on gold is modeled on the basis of the features of the molecular arrangement shown in Figure 11c. The schematic structure, with respect to the underlying gold surface, is shown in Figure 11d along with the dimensions. It can be seen that the surface structure can be described as a √3 × 3 R30° overlayer structure of 2-naphthalenethiol on gold.

The 2-Naphthalenethiol Dimer

π-Stacking is a common descriptor for face-to-face attractive forces between aromatic hydrocarbons. However, the physical origin of this interaction remains debatable. Here we examined π-stacking in a model homodimer formed by two thiol-substituted naphthalene rings. Two isomers of the 2-naphthalenethiol dimer were discovered using rotational spectroscopy, sharing a parallel-displaced crossed orientation and absence of thiol–thiol hydrogen bonds. The monomer of 2-naphthalenethiol adopts two planar cis or trans conformations, depending on the orientation of the thiol group. The results constitute the first rotational detection of π-stacking isomerism in bicyclic aromatic hydrocarbons, offering insight on the PES and the structural and electronic properties of these weak noncovalent interactions. cis-2-Naphthalenethiol is the global minimum but quite similar in energy to the trans conformer. For the 2-naphthalenethiol dimer, 47 cis/cis (CC), cis/trans (CT), or trans/trans (TT) structures were investigated computationally. The noncovalent interactions (NCIs in the 2-naphthalenethiol dimers have been analyzed using structural, energetic, and electronic information. Despite only a few bicyclic aromatic hydrocarbon dimers having been detected so far in the gas phase, some structural patterns now become apparent.[3]

In conclusion, gas-phase intermolecular clusters constitute chemically specific models of molecular aggregation. However, most studies have focused on hydrogen-bonding, and the observation of π-stacking aggregates has remained elusive. The detection of the 2-naphthalenethiol dimer significantly expands our understanding of π-stacking on substituted bicyclic aromatic hydrocarbons, offering valuable insight about their electronic properties, energetics, noncovalent interactions, and internal dynamics. Several conclusions are worth noticing. The 2-naphthalenethiol dimer maintains the π-stacking arrangement predicted for naphthalene, but its shallow PES increases in complexity and difficulty, offering a large number of low-lying isomers in the sub-kJ mol–1 window, difficult to model computationally. However, the substituent effect of the thiol group is mostly noticed in the increased dimer stabilization compared to the naphthalene or naphthol dimers (increase of +53% or +12%, respectively, in complexation energy). The energy decomposition analysis confirms the dominant character of dispersion forces, common to the three π-stacking structures and distinctive element with respect to hydrogen-bonded clusters. π-Stacking interactions are described through NCI plots as extended diffuse interactions, with localized attractive pockets compatible with the recent descriptions balancing dispersion forces and Pauli repulsion.

References

[1]Shin KO, Park K. A Newly Developed HPLC-UV/Vis Method Using Chemical Derivatization with 2-Naphthalenethiol for Quantitation of Sulforaphane in Rat Plasma. Molecules. 2021 Sep 8;26(18):5473. doi: 10.3390/molecules26185473. PMID: 34576944; PMCID: PMC8467300.

[2]Ganesh, V, and V Lakshminarayanan. “Scanning tunneling microscopy, Fourier transform infrared spectroscopy, and electrochemical characterization of 2-naphthalenethiol self-assembled monolayers on the Au surface: a study of bridge-mediated electron transfer in Ru(NH3)6(2+)/Ru(NH3)6(3+) redox reactions.” The journal of physical chemistry. B vol. 109,34 (2005): 16372-81. doi:10.1021/jp052489u

[3]Saragi RT, Calabrese C, Juanes M, Pinacho R, Rubio JE, Pérez C, Lesarri A. π-Stacking Isomerism in Polycyclic Aromatic Hydrocarbons: The 2-Naphthalenethiol Dimer. J Phys Chem Lett. 2023 Jan 12;14(1):207-213. doi: 10.1021/acs.jpclett.2c03299. Epub 2022 Dec 30. PMID: 36583611; PMCID: PMC9841560.