Two-dimensional Nuclear Overhauser Effect Research Articles

Enhancing the efficacy of monolaurin against SARS-CoV-2 and influenza A (H1N1) with a nanoemulsion formulation

Monolaurin was utilized to formulate temperature-driven phase inversion nanoemulsions containing lesser galangal essential oil, fixed oil, and Cremophor RH40, with aim for eradicating enveloped viruses. Results showed that the droplet size of the nanoemulsion depended on lesser galangal essential oil–fixed oil ratio, monolaurin concentration, and oil concentration. Nanoemulsions prepared from lesser galangal essential oil–perilla oil (60:40) exhibited approximately 50-nm nanosized droplets and high entrapment efficiency (98.68 % ± 2.45 %). After storage at 25 °C for 1 year, droplet size did not vary significantly from the initial size, and monolaurin content was >95 %, indicating good physical and chemical stability. The monolaurin was located at the oil–water interface as indicated by a two-dimensional nuclear Overhauser effect nuclear magnetic resonance spectroscope and computer simulation. The 0.2% w/v monolaurin nanoemulsion inhibited SARS-CoV-2 and influenza A (H1N1) viruses with efficacy more than 3 log reduction (99.90 %) and low cytotoxicity. Hence, the monolaurin nanoemulsion can successfully eradicate enveloped viruses, especially SARS-CoV-2 and influenza A (H1N1).

Insights into dynamic properties of water in lipidic cubic phases by 2D nuclear Overhauser effect (NOE) NMR spectroscopy

Two-dimensional NOE (nuclear Overhauser effect) NMR spectroscopy was employed to investigate the dynamic properties of water within lyotropic bicontinuous lipidic cubic phases (LCPs) formed by monoolein (MO). Experiments observed categorically different effective residence times of water molecules: (i) in proximity to the glycerol moiety of MO, and (ii) adjacent to the hydrophobic chain towards the hydrocarbon tail of MO, as evidenced by the opposite signs of intermolecular NOE cross peaks between protons of water and those of MO in 2D 1H–1H NOESY spectra. Spectroscopic data delineating the different effective residence times of water molecules within both the gyroid (QIIG) and diamond (QIID) phase groups corresponding to hydration levels of 35 and 40 wt%, respectively, are presented. Additionally, an increase in effective residence time of water molecules in proximity to the glycerol moiety of MO in LCPs was observed upon storage at ambient temperature and in the presence of an additive lipid, cholesterol. Atom-specific NOE build-up curves for protons of water and those of MO are also given. The results presented herein provide new insight into the physicochemical properties and behaviour of water in LCPs, and demonstrate an additional avenue for experimental study of water–lipid interactions and hydration dynamics in model membranes and nanomaterials using 2D NOE NMR spectroscopy.

Investigation of the Spatial Structure of Flufenamic Acid in Supercritical Carbon Dioxide Media via 2D NOESY

The search for new forms of already known drug compounds is an urgent problem of high relevance as more potent drugs with fewer side effects are needed. The trifluoromethyl group in flufenamic acid renders its chemical structure differently from other fenamates. This modification is responsible for a large number of conformational polymorphs. Therefore, flufenamic acid is a promising structural modification of well-known drug molecules. An effective approach in this field is micronization, employing "green" supercritical fluid technologies. This research raises some key questions to be answered on how to control polymorphic forms during the micronization of drug compounds. The results presented in this work demonstrate the ability of two-dimensional nuclear Overhauser effect spectroscopy to determine conformational preferences of small molecular weight drug compounds in solutions and fluids, which can be used to predict the polymorphic form during the micronization. Quantitative analysis was carried out to identify the conformational preferences of flufenamic acid molecules in dimethyl sulfoxide-d6 medium at 25 °C and 0.1 MPa, and in mixed solvent medium containing supercritical carbon dioxide at 45 °C and 9 MPa. The data presented allows predictions of the flufenamic acid conformational preferences of poorly soluble drug compounds to obtain new micronized forms.

A Tandem Semipinacol Rearrangement/Aldehyde Arylation or Alkylation of Trisubstituted 2,3-Epoxy Alcohols with Grignard Reagents for Functionalized 1,3-Diols

A tandem semipinacol rearrangement/aldehyde arylation or alkylation reaction leading to formation of functionalized 1,3-diols bearing three consecutive tertiary stereocenters is identified from the reaction of various new trisubstituted 2,3-epoxy alcohols with numerous Grignard reagents. This reaction is useful for stereoselective construction of three consecutive tertiary stereocenters. The observed 1,3-diols exist in the anti configuration, which is confirmed by two-dimensional nuclear Overhauser effect spectroscopy, the crystal structure of acetonide of 1,3-diol analogue 3ai, and further density functional theory studies.

Supramolecular Nanohelix Fabricated by Pillararene-Based Host–Guest System for Chirality Amplification, Transfer, and Circularly Polarized Luminescence in Water

Supramolecular Nanohelix Fabricated by Pillararene-Based Host–Guest System for Chirality Amplification, Transfer, and Circularly Polarized Luminescence in Water

Stable Diarylamine-Substituted Tris(2,4,6-trichlorophenyl)methyl Radicals: One-Step Synthesis, Near-Infrared Emission, and Redox Chemistry

Stable Diarylamine-Substituted Tris(2,4,6-trichlorophenyl)methyl Radicals: One-Step Synthesis, Near-Infrared Emission, and Redox Chemistry

Mechanistic Investigation of Drug Supersaturation in the Presence of Polysorbates as Solubilizing Additives by Solution Nuclear Magnetic Resonance Spectroscopy.

The introduction of solubilizing additives has historically been an attractive approach to address the ever-growing proportion of poorly water-soluble drug (PWSD) compounds within the modern drug discovery pipeline. Lipid-formulations, and more specifically micelle formulations, have garnered particular interest because of their simplicity, size, scalability, and avoidance of solid-state limitations. Although micelle formulations have been widely utilized, the molecular mechanism of drug solubilization in surfactant micelles is still poorly understood. In this study, a series of modern nuclear magnetic resonance (NMR) methods are utilized to gain a molecular-level understanding of intermolecular interactions and kinetics in a model system. This approach enabled the understanding of how a PWSD, 17β-Estradiol (E2), solubilizes within a nonionic micelle system composed of polysorbate 80 (PS80). Based on one-dimensional (1D) 1H chemical shift differences of E2 in PS80 solutions, as well as intermolecular correlations established from 1D selective nuclear Overhauser effect (NOE) and two-dimensional NOE spectroscopy experiments, E2 was found to accumulate within the palisade layer of PS80 micelles. A potential hydrogen-bonding interaction between a hydroxyl group of E2 and a carbonyl group of PS80 alkane chains may allow for stabilizing E2-PS80 mixed micelles. Diffusion and relaxation NMR analysis and particle size measurements using dynamic light scattering indicate a slight increase in the micellar size with increasing degrees of supersaturation, resulting in slower mobility of the drug molecule. Based on these structural findings, a theoretical orientation model of E2 molecules with PS80 molecules was developed and validated by computational docking simulations.

Aerobic α-hydroxylation of 2-Me-1-tetralone in 1-alkyl-3-methylimidazolium ionic liquids.

The aerobic α-hydroxylation of 2-Me-1-tetralone was investigated in imidazol-based ionic liquids (ILs), where reactions in 1-alkyl-3-methylimidazolium tetrafluoroborates were found to generate considerable products. By correlating the conversion at 2 h with viscosity, relative permittivity and the ET(30) value of ILs, we found that the local polarity in ILs represented by the ET(30) value or the chemical shift of α-proton at the substrate was the critical factor influencing the reaction rate. Furthermore, two-dimensional nuclear Overhauser effect spectroscopy (2D NOESY) was used to characterize the distribution of 2-Me-1-tetralone in ILs. As a result, the mesoscopic structures in ILs were recommended to have crucial influences on the distribution of the substrate in ILs, and the caused local polarity could affect the activation of 2-Me-1-tetralone. These findings revealed the solvent effects of ILs with different structures on the α-hydroxylation of 2-Me-1-tetralone, and may encourage the explorations of more types of aerobic oxidations in ILs.

The Influence of the Strength of Drug-Polymer Interactions on the Dissolution of Amorphous Solid Dispersions.

In an earlier report, ionic interactions between ketoconazole (KTZ), a weakly basic drug, and poly(acrylic acid) (PAA), an anionic polymer, resulted in a dramatic decrease in molecular mobility as well as reduced crystallization propensity of amorphous solid dispersion (ASD) in the solid state. On the other hand, weaker dipole-dipole interactions between KTZ and polyvinylpyrrolidone (PVP) resulted in ASDs with higher crystallization propensity (Mistry Mol Pharm., 2015, 12 (9), 3339-3350). In this work, we investigated the behavior of the ketoconazole (KTZ) solid dispersions in aqueous media. In vitro dissolution tests showed that the PAA ASD maintained the level of supersaturation for a longer duration than the PVP ASD at low polymer contents (4-20% w/w polymer). Additionally, the PAA ASDs were more resistant to drug crystallization in aqueous medium when measured with synchrotron X-ray diffractometry. Two-dimensional 1H nuclear Overhauser effect spectroscopy (NOESY) NMR cross peaks between ketoconazole and PAA confirmed the existence of drug-polymer interactions in D2O. The interaction was accompanied by a reduced drug diffusivity as monitored by 2D diffusion ordered spectroscopy (DOSY) NMR and enthalpy-driven when characterized by isothermal titration calorimetry (ITC). On the other hand, drug-polymer interactions were not detected between ketoconazole and PVP in aqueous solution, with NOESY, DOSY, or ITC. The results suggest that interactions that stabilize ASDs in the solid state can also be relevant and important in sustaining supersaturation in solution.

Cation–Anion and Anion–CO2 Interactions in Triethyl(octyl)phosphonium Ionic Liquids with Aprotic Heterocyclic Anions (AHAs)

Ionic liquids with aprotic heterocyclic anions (AHAs) have been developed for postcombustion CO2 capture applications. The anions of AHA ILs play a significant role in tuning anion-CO2 complexation. In addition, AHAs are able to trigger the abstraction of acidic protons located at the α position of phosphonium cations by forming hydrogen bonds between cations and anions, eventually leading to cation-driven CO2 complexation. Here we investigate the role of the anion in cation-anion hydrogen bonding and ylide formation. Using CO2 uptake measurements, 31P nuclear magnetic resonance (NMR), attenuated total reflection-Fourier transform infrared (ATR-FTIR) deuterium exchange equilibrium and rates, two-dimensional nuclear Overhauser effect spectroscopy (2D NOESY), and density functional theory calculations, we show that the key is the proximity of the negatively charged nitrogen atoms on the anion to the α protons, which is governed not just by anion basicity but by sterics. Thus, we show that triethyl(octyl)phosphonium 3-methyl-5-trifluoromethylpyrazolide is much more effective in hydrogen-bonding with and deprotonating the cation than the equivalent [P2228] ILs with more basic 2-cyanopyrrolide and 3-trifluoromethylpyrazolide anions.

Pillar[5]arene-Based [2]Rotaxane: Synthesis, Characterization, and Application in a Coupling Reaction.

Mechanically interlocked molecules are a class of smart supramolecular species because of their interesting topological structure and application in various areas, such as biology and nanoscience. In this work, we used "multicomponent reaction" to fabricate a new [2]rotaxane based on pillar[5]arene from different small-sized molecules. The molecular structure of the obtained [2]rotaxane R was confirmed by 1H and 13C NMR, high-resolution electrospray ionization mass spectrometry, two-dimensional nuclear Overhauser effect spectroscopy, and density functional theory studies. Interestingly, the [2]rotaxane-based organometallic cross-linked catalyst (Pd@R) was easily constructed via the coordination between triazole groups and Pd(NO3)2. Pd@R proved to be a good catalyst for the Suzuki-Miyaura coupling reaction with excellent stability and repeatability.

Micellization Behavior of Conventional Cationic Surfactants within Glycerol-Based Deep Eutectic Solvent.

The aggregation behavior of two cationic surfactants, i.e., cetyldimethylethanolammonium bromide (CDMEAB) and cetyltributylphosphonium bromide (CTBPB), within an aqueous deep eutectic solvent (DES) is studied. The synthesized DES is composed of 1:2 mole ratio of choline chloride and glycerol and is further characterized by Fourier transform infrared (FTIR) and 1H NMR spectroscopy techniques. The critical micellar concentration (CMC), micellar size, and intermolecular interaction in surfactants within Gly-based DES solutions are investigated by various techniques including surface tension, conductivity, fluorescence, dynamic light scattering (DLS), FTIR, 1H NMR, and two-dimensional (2D) nuclear Overhauser effect spectroscopy (NOESY). The various interfacial properties and thermodynamic parameters are determined in the presence of 5 wt % glyceline (Gly)-based DES in an aqueous solution. The CMC, aggregation number (Nagg), and Stern–Volmer constant (Ksv) have also been determined by a steady-state fluorescence method. DLS is used to obtain information regarding the size of the aggregates formed by the cationic surfactants in DES solutions. FTIR spectroscopy is used to study the surfactant–DES interactions that tune the micellar structure of the surfactants within the Gly-based DES solution. The functional groups involved in the interactions (H-bonding and electrostatic) are the head groups (HO–CH2–CH2–N+ ion for CDMEAB and quaternary phosphonium (P+) ion for CTBPB) of the surfactants with the −OH-containing Gly DES. The hydrophobic moieties are involved in the hydrophobic interactions. The 1H NMR data show that differences in chemical shifts can provide significant information about the interactions taking place within the system. 1H NMR and NOESY techniques are further employed to strengthen our claim on the feasible structural arrangements within the aqueous surfactant–DES self-assembled structures. It is observed that both the cationic surfactants, i.e., CDMEAB and CTBPB, form self-assembled nanostructures in the Gly-based DES solutions. The present results are expected to be useful for colloidal solutions of DES and their mixtures with water.

Interpreting In Vitro Release Performance from Long-Acting Parenteral Nanosuspensions Using USP-4 Dissolution and Spectroscopic Techniques.

Injectable sustained release dosage forms have emerged as desirable therapeutic routes for patients that require life-long treatments. The prevalence of drug molecules with low aqueous solubility and bioavailability has added momentum toward the development of suspension-based long-acting parenteral (LAP) formulations; the previously undesirable physicochemical properties of Biopharmaceutics Classification System (BCS) Class II/IV compounds are best suited for extended release applications. Effective in vitro release (IVR) testing of crystalline suspensions affirms product quality during early-stage development and provides connections with in vivo performance. However, before in vitro-in vivo correlations (IVIVCs) can be established, it is necessary to evaluate formulation attributes that directly affect IVR properties. In this work, a series of crystalline LAP nanosuspensions were formulated with different stabilizing polymers and applied to a continuous flow-through (USP-4) dissolution method. This technique confirmed the role of salt effects on the stability of polymer-coated nanoparticles through the detection of disparate active pharmaceutical ingredient (API) release profiles. The polymer stabilizers with extended hydrophilic chains exhibited elevated intrapolymer activity from the loss of hydrogen-bond cushioning in dissolution media with heightened ionic strength, confirmed through one-dimensional (1D) 1H NMR and two-dimensional nuclear Overhauser effect spectroscopy (2D NOESY) experiments. Thus, steric repulsion within the affected nanosuspensions was limited and release rates decreased. Additionally, the strength of interaction between hydrophobic polymer components and the API crystalline surface contributed to suspension dissolution properties, confirmed through solution- and solid-state spectroscopic analyses. This study provides a unique perspective on the dynamic interface between the crystalline drug and aqueous microenvironment during dissolution.

Photoresponsive Behavior of Wormlike Micelles Constructed by Gemini Surfactant 12-3-12·2Br- and Different Cinnamate Derivatives.

The photoresponsive wormlike micelles constructed by Gemini surfactants and cinnamate derivatives play a great role in the field of smart materials. However, how the structure of cinnamate derivatives affects the photoresponsive behavior of micelles is still a hotspot for scientists to research. Here, three kinds of aromatic salts with different ortho-substituted groups including trans- o-methoxy cinnamate ( trans-OMCA), trans- o-hydroxy cinnamate ( trans-OHCA), and trans-cinnamate ( trans-CA) were introduced into Gemini surfactant 12-3-12·2Br- aqueous solutions to construct photoresponsive wormlike micelles through their noncovalent interactions. Their properties were researched using the rheological method, cryo-transmission electron microscopy, and 1H NMR and two-dimensional nuclear Overhauser effect spectra. The results show that these cinnamate derivatives could well construct wormlike micelles with 12-3-12·2Br-. Furthermore, subtle differences in the ortho substituents' structure have a significant effect on the photoresponsive behavior of formed wormlike micelles. Specifically, the zero viscosity (η0) of 40 mM 12-3-12·2Br-/24 mM trans-OHCA mixed solution decreases from 26.72 to 2.6 Pa·s with the shortening of the length of wormlike micelles after UV irradiation. Correspondingly, the η0 for the same ratio of 12-3-12·2Br-/ trans-OMCA decreases from 2.42 to 0.06 Pa·s and the wormlike micelles are transited into rodlike micelles and even spherical micelles after the same UV irradiation time. However, the variation of wormlike micelles in the 12-3-12·2Br-/ trans-CA system induced by UV light is not obvious with η0 being maintained at around 2.89 Pa·s. This study will help us better understand the effects of chemical groups on macrophenomena and microinteraction for micellar systems. It provides a theoretical basis for the construction of photoresponsive micelles, thus widening their application in the field of soft materials.

Studies on the preparation and photostability of avobenzone and (2-hydroxy)propyl-β-cyclodextrin inclusion complex

The inclusion complex of avobenzone and (2-hydroxy)propyl-β-cyclodextrin (2-HP-β-CD) was prepared successfully. The effects of the inclusion behavior of avobenzone with 2-HP-β-CD were investigated in both solution and the solid state with the following methods: UV–vis spectrophotometry (UV–vis), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TG), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM), proton nuclear magnetic resonance (1H-NMR) and two-dimensional rotational frame nuclear overhauser effect spectroscopy (2D ROESY). The photostability of avobenzone and its inclusion complex were both investigated by UV–vis spectrophotometry. The Benesi-Hildebrand’s method showed that avobenzone formed 1:2 stoichiometric inclusion complex with 2-HP-β-CD. The solubility, thermal stability and the photostability of avobenzone were all improved after encapsulating by the 2-HP-β-CD. Therefore, it can be a potentially promising way to promote its cosmetic preparations in UVA sunscreen.

Binding and structure-kinetic relationship analysis of selective TLR4-targeted immunosuppressive self-assembling heparin nanoparticles

Self-assembling aliphatic heparin derivatives were shown to inhibit the immune system by antagonizing Toll-like receptor 4/myeloid differentiation protein 2 (TLR4/MD2). In the present study, glycol split heparin–d-erythro-sphingosine conjugates (NAHNP) and its regioselectively desulfated derivatives with shortened aliphatic chains were investigated regarding their biophysical properties in the interaction with TLR4/MD2. Two-dimensional nuclear Overhauser effect spectroscopy studies showed that upon glycol splitting, the heparin backbone gains extra adaptability that facilitates binding to proteins. However, unlike native heparin or glycol split non-anticoagulant heparin (NAH), hydrophobic derivatization of NAH forces sulfated iduronic acid residues to change configuration from a 2S0 skew-boat to a 1C4 chair form. Whereas neither heparin nor NAH had any appreciable effect, NAHNP significantly inhibited lipopolysaccharide-induced activation of the NF-κB transcription factor. We showed that NAHNP binds to TLR4/MD2 with an affinity of 62.3 nM. In line with computational studies, biosensor-based structure-kinetic relationship studies demonstrated that 6-O-sulfo groups of d-glucosamine residue were essential in binding to arginines of both TLR4 and MD2 domains of the receptor complex. The desulfation of 6-O-sulfo groups decreases the association kinetics from 4.2 × 104 M−1 s−1 to 3.8 × 103 M−1 s−1, which results in a decreased affinity of 800 nM. Two aliphatic chains of NAHNP bound to the MD2 pocket similarly to lipopolysaccharide. A decrease in chain length resulted in a loss of inhibitory activity on NF-κB transcription and binding affinity to TLR4/MD2. In conclusion, the present study characterizes the immunosuppressive effect of aliphatic heparin derivatives and provides a promising strategy to develop selective immunosuppressants for acute and chronic inflammatory disorders.

5-Hydroxy-3-(4-hydroxyphenyl)-8,8-dimethyl-6-(3-methylbut-2-enyl)pyrano[2,3-h]chromen-4-one

Natural and semi-synthetic compounds are being studied as novel phosphodiesterase 5 (PDE5) inhibitors for the treatment of erectile dysfunction, pulmonary hypertension, and lower urinary symptoms. Maclura pomifera is a source of flavonoids, one of the main classes of molecules investigated for these purposes. The extraction of the natural isoflavone osajin and its modification to obtain a semi-synthetic derivative are described in this short note. 1H and 13C-nuclear magnetic resonance spectroscopy (NMR), mass spectrometry, high-performance liquid chromatography (HPLC) and spectroscopic characterization of the title compound are also hereby provided. Two-dimensional (2D) nuclear Overhauser effect spectroscopy (NOESY) NMR, supported by in silico conformational studies, was used to achieve a complete assignment of the proton signals, assessing the correct chemical structure of the compound. Heteronuclear single quantum coherence spectroscopy (HSQC) and heteronuclear multiple bond correlation (HMBC) NMR experiments were performed to assign 13C chemical shifts. Calculated chemical properties and preliminary in silico docking suggest that this molecule might be a promising candidate as PDE5 inhibitor.

Effect of hydrophilically modified ibuprofen on thermoresponsive gelation of pluronic copolymer

This paper concerns the effect of hydrophilically modified ibuprofen (IBU-PEO9, IP400), which is an amphiphilic anti-inflammatory drug, on the thermoresponsive gelation of Pluronic F127 (poly(ethylene oxide) poly(propylene oxide) poly(ethylene oxide), PEO97-PPO68-PEO97). Rheology, small angle X-ray scattering (SAXS), 1H nuclear magnetic resonance (1H NMR), two-dimensional nuclear Overhauser effect spectroscopy (2D-NOESY), and spin-lattice relaxation time (T1) are applied to investigate the interaction mechanism on both macroscopic scale and molecular level. The results show that the addition of IP400 strongly affects the gelation and the microstructure of gel. The addition of IP400 at low concentration facilitates the temperature-induced gelation of F127, while the body centered cubic structure of the gel is persevered. The results confirm that the hydrophobic interactions between PPO chains of F127 and the hydrophobic tails of IP400 are dominant in the enhancement of the micellization and subsequently the gelation of F127. At higher IP400 concentration, the promotion of the temperature-induced gelation by IP400 diminishes, and the gel with more primitive structure and weaker strength is formed. This is because the insertion of IP400 into F127 micelles results in the enhanced separation and mobility of PEO chains of F127, substantially the entanglement and interpenetration of the PEO chains are disturbed within the cubic structure. This information sheds some light on the prediction of the controlled release patterns of the modified drug in the mixed system.

Comparative Structural Characterization of Spiral Dextrin Inclusion Complexes with Vitamin E or Soy Isoflavone

In this study, the preparation and structural properties of spiral dextrin (SD)/vitamin E and SD/soy isoflavone inclusion complexes were studied. SD was obtained from debranched normal maize starch using isoamylases. After fractionation using a novel method of gradient ethanol precipitation, SD was separated into different fractions, among which SD-40 was found to be the optimal host molecule to prepare SD inclusion complexes with vitamin E or soy isoflavone. X-ray diffraction (XRD) and 13C cross-polarization magic angle spinning nuclear magnetic resonance (NMR) suggested that the crystalline structures of SD-40/vitamin E and SD-40/soy isoflavone were V6II and V6III types, respectively. Small-angle X-ray scattering revealed that the SD-40/vitamin E inclusion complex formed a tighter and more compact crystallite than the SD-40/soy isoflavone inclusion complex. Furthermore, the connection structures of inclusion complexes were investigated by two-dimensional nuclear Overhauser effect spectroscopy NMR, indicating that part of vitamin E with an alkyl chain was encapsulated in the helix cavity of SD-40, whereas the aromatic ring B of the soy isoflavone molecule was complexed by the helix cavity and screw of SD.

Role of the spacer of Gemini surfactants in solubilization into their micelles

We report the role of a spacer chain in gemini surfactants for solubilization of poor soluble compounds to the aqueous medium. Solubilization of n-alkylbenzenes into micellar solutions of alkanediyl-1,s-bis(dimethyltetradecylammonium bromide) (14-s-14,2Br−, s=2, 6, and 12) has been studied in the temperature range from 288.2 to 308.2K. The equilibrium concentrations of all the solubilizates are determined spectrophotometrically. The solubility of the solubilizates remains constant below the critical micelle concentration (cmc) and increases linearly with an increase in the surfactant concentration above the cmc. The hydrodynamic diameter of the micellar aggregates with or without the solubilizates is measured by means of dynamic light scattering (DLS). The enthalpy, entropy, and Gibbs energy changes for the solubilization of n-alkylbenzenes have been calculated to evaluate a driving force of a transfer of the solubilizates into the micelle. These results indicate that the driving force and solubilization site in the aggregates are changed depending on the spacer chain length of surfactants. Furthermore, the inner core of the solubilized aggregates has been investigated by Fourier transform infrared (FTIR) spectra and two-dimensional nuclear Overhauser effect spectroscopy (2-D NOESY).