Exploring Crystal-Phase Molecular Dynamics of the Low-Viscous Mesogen 6CHBT: A Combined FFC and High-Field NMR Relaxometry Investigation.

The molecular dynamics study of thermotropic mesogens exhibiting the crystal phases is valuable in unraveling the complex global (collective) and local (noncollective) motions executed by liquid crystal molecules, which would further advance the existing knowledge on orientationally disordered crystalline (ODIC) phases. Toward the fulfillment of such a task, a combined nuclear magnetic resonance (NMR) relaxometry approach employing the fast field cycling (FFC) NMR (10 kHz-30 MHz) and high-field pulsed NMR (400 MHz) techniques is utilized to sample the broad frequency range offered by molecular motions in the crystal phase of 4-(trans-4'-n-hexylcyclohexyl)-isothiocyanatobenzene (6CHBT). The validity of the observed relaxation data is tested and interpreted by the Bloembergen-Purcell-Pound (BPP) model involving the superposition of four mutually independent Lorentzian spectral densities, reflecting molecular dynamical processes on different time scales. The salient feature of the detailed analysis reveals that the lengthening of temporal dynamics in the crystal phase due to molecular rotations by jumps, which are of intermolecular origin, is evident and further supports the presence of collective-like local dynamics. The analysis does permit decoupling of the molecular reorientations about their short axes (∼100 ns) as well as long axes (∼50 ns) and methyl group rotations (∼0.5 ns) on distinct time scales. The activation energies for reorientations about the short axes and methyl group rotations are found to be 27.3 ± 2.7 and 15.8 ± 1.1 kJ/mol, respectively. The fast methyl rotations in the crystal phase of 6CHBT obtained from FFC NMR are further well complemented by high-field NMR, where 1H NMR line shapes are relatively narrow when compared to those of the nematic phase.

Comprehensive NMR Investigation of Imidazolium-Based Ionic Liquids [BMIM][OSU] and [BMIM][Cl] Impact on Binding and Dynamics of the Anticancer Drug Doxorubicin Hydrochloride.

For the design of an efficient drug delivery system utilizing an ionic liquid (IL) as a carrier, it is prudent to gain molecular/atomistic level insights of a drug with IL in terms of binding and dynamics. In this scenario, the influence of anionic counterpart of imidazolium-based ILs, namely, 1-butyl-3-methyl-imidazolium octyl sulfate [BMIM][OSU] and 1-butyl-3-methyl-imidazolium chloride [BMIM][Cl] in their submicellar region ([IL] = 20 mM) on the model water-soluble anticancer drug doxorubicin hydrochloride (DOX) was probed by employing an arsenal of nuclear magnetic resonance (NMR) approaches. The salient feature of the present study includes the significant interaction of DOX with [BMIM][OSU], whereas the lack of such an interaction with [BMIM][Cl] is gauged by 1H NMR translation self-diffusometry and is further corroborated by 13C chemical shift perturbation. The two-step model was utilized to estimate the bound fraction (pb) and equivalent partition coefficient (K) of DOX with [BMIM][OSU]. A combination of selective and nonselective spin-lattice relaxation rates (R1SEL and R1NS, respectively) enables to gauze the significant interaction of DOX with [BMIM][OSU] over [BMIM][Cl]. Furthermore, 1D transient and truncated driven nuclear Overhauser enhancement (NOE) data analyses in the initial rate limit permits the evaluation of the cross-relaxation efficacy of DOX with the investigated ILs. An Arrhenius-type temperature dependence of the drug's self-diffusion was observed for DOX, DOX-[BMIM][OSU], and DOX-[BMIM][Cl] aqueous mixtures and the corresponding activation energies were evaluated.

Improving Hydrophobicity of Collagen with Silica Nanoparticles: Probing a Noncovalent Approach.

Collagen-based materials have a wide range of applications in wound care, tendon repair, cartilage repair, etc. Improving certain properties such as hydrophobicity can diversify the application areas. In this work, we investigated the noncovalent interactions of suitably functionalized silica nanoparticles with collagen for the possibility of improving hydrophobicity. Functionalization on silica nanoparticles was achieved via Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) or "click" reaction using surface grafting methods. Furthermore, we synthesized two different silica nanoparticles (SiNPs) functionalized with the fluorine-containing substrate or only with an aryl moiety (silica-g-4EMB and silica-g-ETFMB) for comparison. The functionalized SiNPs immobilized along with the model system trans-4-hydroxy-l-proline (HPA) (usually present in abundant quantities in collagen) have been probed using nuclear magnetic resonance (NMR) spin relaxation to appreciate the influence of SiNPs on HPA. Furthermore, we effectively utilized a saturated transfer difference (STD) NMR experiment to measure the interaction parameters between judiciously functionalized silica nanoparticles and substrates of interest. In essence, such a detailed study on noncovalent interactions employing an arsenal of experimental approaches facilitated the immobilization of suitably functionalized silica nanoparticles to collagen and leather (where collagen is a major constituent), leading to improvements in hydrophobicity.

pH-Induced Biophysical Perspectives of Binding of Surface-Active Ionic Liquid [BMIM][OSU] with HSA and Dynamics of the Formed Complex.

The influence of pH on the human serum albumin (HSA) interaction with ionic liquid (IL)1-butyl 3-methylimidazolium octyl sulfate ([BMIM][OSU]) at its sub-micellar concentration of 5 mM (well below CMC ∼31 mM at 25 °C) in aqueous solution has been monitored employing different methods, viz., circular dichroism (CD), fluorescence, electrokinetic determination of the zeta potential (ZP), nuclear magnetic resonance (NMR), small-angle neutron scattering (SANS), and molecular docking (MD). CD analysis indicated a noticeable reduction of the α-helical content of HSA by IL at pH 3. A significant interaction of the anionic part of IL with HSA was evident from the 1H chemical shifts and saturation transfer difference (STD) NMR. A strong binding between IL and HSA was observed at pH 3 relative to pH 5, revealing the importance of electrostatic and hydrophobic interactions assessed from global binding affinities and molecular correlation times derived from STD NMR and a combined selective/nonselective spin-relaxation analysis, respectively. ZP data supported the electrostatic interaction between HSA and the anionic part of IL. The nature of IL self-diffusion with HSA was assessed from the translational self-diffusion coefficients by pulse field gradient NMR. SANS results revealed the formation of prolate ellipsoidal geometry of the IL-HSA complex. MD identified the preferential binding sites of IL to the tryptophan centers on HSA. The association of IL with HSA was supported by fluorescence measurements, in addition to the structural changes that occurred in the protein by the interaction with IL. The anionic part of IL contributed a major interaction with HSA at the pH levels of study (3, 5, 8, and 11.4); at pH > 8 (effectively 11.4), the protein also interacted weakly with the cationic component of IL.

NMR Studies on the Interaction of Anticancer Drug Doxorubicin with Membrane Mimetic SDS.

In the formulation of efficient drug delivery systems, it is essential to unravel the structural and dynamical aspects of the drug's interaction with biological membranes. This has been done for the anticancer drug-membrane system comprising doxorubicin hydrochloride (DOX), a water-soluble anticancer drug, and the micellar sodium dodecyl sulfate (SDS), the latter serving as a useful mimic for membrane proteins. Using a multimodal NMR approach involving 1H, 2H, and 13C as probe nuclei and through the determination of chemical shifts, spin-relaxation, nuclear Overhauser enhancements (NOE), and translational self-diffusion (SD), the binding characteristics of the DOX with SDS have been determined. The perturbation to 13C chemical shifts of SDS indicate the penetration of DOX into the SDS micelle, which is further revealed by 1H-1H NOESY and SD measurements. 2H spin-relaxation measurements and their analysis using a two-step model show DOX induced SDS micellar volume changes, which determine the correlation times involved in the DOX-SDS mobility.

Molecular Dynamics in the Lyophases of Copolymer P123 Investigated with FFC NMR Relaxometry.

Associative block copolymers of the type (EO) x(PO) y(EO) x (where EO and PO represent ethylene and propylene oxides, respectively) in aqueous solution have far reaching commercial applications such as solubilization, controlled-drug delivery, etc. The molecular dynamics of a self-associating triblock copolymer (EO)20(PO)70(EO)20 (known as P123 with a molecular weight of ∼5800), in aqueous solution (D2O), consisting of various lyotropic liquid crystalline phases such as isotropic micellar, cubic, hexagonal, and lamellar phases, is investigated using the fast field cycling nuclear magnetic resonance (FFC NMR) relaxometry technique in the Larmor frequency range from 5 kHz to 30 MHz. A nuclear spin-relaxation model consisting of chain modes (Rouse modes) and order fluctuation (OF) modes typical for polymers and liquid crystals, respectively, is considered to explain the observed proton magnetic relaxation dispersion (PMRD) data in the lyophases under investigation. The PMRD analysis in both isotropic micellar and cubic phases revealed a Rouse frequency dependence of spin-lattice relaxation rate ( R1), i.e., R1 ∝ -τs ln(ωτs), in the entire frequency range of study. Hexagonal and lamellar phase data show Rouse modes as well as OF modes, leaving the signature of the latter as R1 ∝ ω- p, where p ∼ 0.5 is typical for nematic mesogens. The activation energies were also determined from segmental correlation times in the lyophases of study. To the best of our knowledge, the present FFC NMR relaxometry study is unique and quantitative in unraveling molecular dynamics of the associative copolymer P123 in aqueous solution.

Physicochemical Understanding of Self-Aggregation and Microstructure of a Surface-Active Ionic Liquid [C4mim] [C8OSO3] Mixed with a Reverse Pluronic 10R5 (PO8EO22PO8).

Physicochemical studies on aqueous mixtures of ionic liquids (ILs) and reverse pluronics are limited. Self-aggregation dynamics and microstructure of a surface-active IL (SAIL), 1-butyl-3-methylimidazolium octylsulfate [C4mim] [C8OSO3], in the presence of a reverse pluronic, PO8EO22PO8 (known as 10R5), were studied using isothermal titration calorimetry (ITC), high-resolution nuclear magnetic resonance (NMR), and small-angle neutron scattering (SANS) methods. Also, cryo-/freeze-fracture transmission electron microscopy was employed to determine the microstructures of SAIL/10R5 mixtures. The ITC and NMR results revealed facilitation of SAIL aggregation in the presence of 10R5 forming mixed aggregates as well as free SAIL micelles. 2H spin relaxation rate data pointed out the onset of slow dynamics of the aqueous SAIL/10R5 mixture with an increase in either the former or the latter. Globular morphologies of the mixed species as well as their individual components were corroborated from the measurements. The preferential location of interaction of the SAIL with the 10R5 was identified from 13C NMR chemical shift findings to be in the interfacial region of the assembled SAIL. The formed species were mixed interacted aggregates but not mixed micelles that arise from mixed surfactants. The physicochemical information acquired herein would enrich the literature on the 10R5/SAIL mixed microheterogeneous systems having importance in the making of useful green drug carrier systems and templates for the synthesis of nanomaterials.

Molecular Level Insights on Collagen-Polyphenols Interaction Using Spin-Relaxation and Saturation Transfer Difference NMR.

Interaction of small molecules with collagen has far reaching consequences in biological and industrial processes. The interaction between collagen and selected polyphenols, viz., gallic acid (GA), pyrogallol (PG), catechin (CA), and epigallocatechin gallate (EGCG), has been investigated by various solution NMR measurements, viz., (1)H and (13)C chemical shifts (δH and δC), (1)H nonselective spin-lattice relaxation times (T1NS) and selective spin-lattice relaxation times (T1SEL), as well as spin-spin relaxation times (T2). Furthermore, we have employed saturation transfer difference (STD) NMR method to monitor the site of GA, CA, PG, and EGCG which are in close proximity to collagen. It is found that -COOH group of GA provides an important contribution for the interaction of GA with collagen, as evidenced from (13)C analysis, while PG, which is devoid of -COOH group in comparison to GA, does not show any significant interaction with collagen. STD NMR data indicates that the resonances of A-ring (H2', H5' and H6') and C-ring (H6 and H8) protons of CA, and A-ring (H2' and H6'), C-ring (H6 and H8), and D-ring (H2″and H6″) protons of EGCG persist in the spectra, demonstrating that these protons are in spatial proximity to collagen, which is further validated by independent proton spin-relaxation measurement and analysis. The selective (1)H T1 measurements of polyphenols in the presence of protein at various concentrations have enabled us to determine their binding affinities with collagen. EGCG exhibits high binding affinity with collagen followed by CA, GA, and PG. Further, NMR results propose that presence of gallic acid moiety in a small molecule increases its affinity with collagen. Our experimental findings provide molecular insights on the binding of collagen and plant polyphenols.