Two-dimensional Nuclear Overhauser Enhancement Spectroscopy Research Articles

Synergism between betaine surfactants under high-salt conditions

Foam properties and surface dilational rheology of single and mixed LHSB (lauramidopropyl hydroxyl sulfobetaine)-OAB (oleic amide propyl betaine) surfactants were measured to investigate the synergism between the two components. Experimental results showed obvious synergistic effects in foam stability, dilational modulus, and phase angle between LHSB and OAB. Moreover, interaction parameters were calculated to quantitatively characterize the synergism. The negative interaction parameters between LHSB and OAB demonstrated that there was an attractive interaction between LHSB and OAB, and the attractive interaction contributed to forming the dense surfactant layer at the liquid/air layer, which in turn improved foam stability. The negative values of parameters reached their maximum when the LHSB: OAB molar ratio ranged from 1:1 to 1:2, the same time the foam stability reached its maximum. The interaction between LHSB and OAB was confirmed by 2D NOSEY (two-dimensional nuclear overhauser enhancement spectroscopy) experiments, the interaction between LHSB and OAB could be attributed to the hydrogen bonding or the electrostatic interaction between the hydrophilic groups of the two surfactants.

Tuning Cationic Micelle Properties with an Antioxidant Additive: A Molecular Perspective.

In this work, we characterize the micellization and morphology transition induced in aqueous cetyltrimethylammonium bromide (CTAB) solution by the addition of the antioxidant propyl gallate (PG) using tensiometry, rheology, and small-angle neutron scattering (SANS) techniques combined with the molecular dynamics (MD) simulation approach. The adsorption of CTAB at the air-water interface in the presence of varying [PG] revealed a progressive decrease in the critical micelle concentration (CMC), while the changes in different interfacial parameters indicated enhancement of the hydrophobicity induced by PG in the CTAB micellar system. The dynamic rheology behavior indicated an increase in the flow viscosity (η) as a function of [PG]. Moreover, the rheological components (storage modulus, G', and loss modulus, G″) depicted the viscoelastic features. SANS measurements depicted the existence of ellipsoidal micelles with varying sizes and aggregation number (Nagg) as a function of [PG] and temperature. Computational simulation performed using density functional theory (DFT) calculations and molecular dynamics (MD) provided an insight into the atomic composition of the examined system. The molecular electrostatic potential (MEP) analysis depicted a close proximity of CTAB, i.e., emphasized favorable interactions between the quaternary nitrogen of CTAB and the hydroxyl group of the PG monomer, further validated by the two-dimensional nuclear Overhauser enhancement spectroscopy (2D-NOESY), which showed the penetration of PG inside the CTAB micelles. In addition, various dynamic properties, viz., the radial distribution function (RDF), the radius of gyration (Rg), and solvent-accessible surface area (SASA), showed a significant microstructural evolution of the ellipsoidal micelles in the examined CTAB-PG system, where the changes in the micellar morphology with a more elongated hydrophobic chain and the increased Rg and SASA values indicated the notable intercalation of PG in the CTAB micelles.

Solid-Phase Microcontact Printing for Precise Patterning of Rough Surfaces: Using Polymer-Tethered Elastomeric Stamps for the Transfer of Reactive Silanes.

We present a microcontact printing (μCP) routine suitable to introduce defined (sub-) microscale patterns on surface substrates exhibiting a high capillary activity and receptive to a silane-based chemistry. This is achieved by transferring functional trivalent alkoxysilanes, such as (3-aminopropyl)-triethoxysilane (APTES) as a low-molecular weight ink via reversible covalent attachment to polymer brushes grafted from elastomeric polydimethylsiloxane (PDMS) stamps. The brushes consist of poly{N-[tris(hydroxymethyl)-methyl]acrylamide} (PTrisAAm) synthesized by reversible addition–fragmentation chain-transfer (RAFT)-polymerization and used for immobilization of the alkoxysilane-based ink by substituting the alkoxy moieties with polymer-bound hydroxyl groups. Upon physical contact of the silane-carrying polymers with surfaces, the conjugated silane transfers to the substrate, thus completely suppressing ink-flow and, in turn, maximizing printing accuracy even for otherwise not addressable substrate topographies. We provide a concisely conducted investigation on polymer brush formation using atomic force microscopy (AFM) and ellipsometry as well as ink immobilization utilizing two-dimensional proton nuclear Overhauser enhancement spectroscopy (1H–1H-NOESY-NMR). We analyze the μCP process by printing onto Si-wafers and show how even distinctively rough surfaces can be addressed, which otherwise represent particularly challenging substrates.

Interaction of Phenyl-Substituted Diazaperylenium with Cucurbit[n]uril: Complex versus Supramolecular Polymer.

A phenyl-substituted diazaperylenediium dication (DAP) was synthesized that shows concentration-dependent aggregation in water. The host–guest complexation of DAP was studied with the macrocyclic host cucurbit[n]uril (n = 7, 8) in water. With CB[7], it forms a 1:2 complex by placing two aryl substituents inside the CB[7]; whereas, with CB[8], a supramolecular polymer is formed. The resulting complex and supramolecular polymer have been characterized by ITC (isothermal titration calorimetry), ESI-MS (electrospray ionization mass spectrometry), 1H NMR (proton nuclear magnetic resonance), 2D NOESY (two-dimensional nuclear Overhauser enhancement spectroscopy), and DOSY (diffusion-ordered spectroscopy) spectra.

Supramolecular redox-responsive substrate carrier activity of a ferrocenyl Janus device

Supramolecular Janus compounds have recently attracted increasing attention owing to their dynamic reversible properties, distinct topological structures, and remarkable physicochemical characteristics, e.g., amphiphilicity, heterofunctionality, and high-density of terminal groups. Herein, a new redox-responsive supramolecular Janus device was designed and synthesized involving β-cyclodextrin and 2-fold ferrocene host-guest interactions. The complex formation was analyzed via one-dimensional 1H NMR and two-dimensional Nuclear Overhauser Enhancement Spectroscopy. FeCl3 and ascorbic acid were used as oxidation and reduction triggers, respectively, to modulate the self-assembly behavior in water through complexation/dissociation of β-cyclodextrin inclusion compounds resulting from redox-conversion of the ferrocenyl guest moieties. The redox-responsiveness of the obtained supramolecular micelles was studied via scanning electron microscopy and dynamic light scattering. Substrate-loading ability of the supramolecular micelles was confirmed with Rhodamine B, and the oxidation of ferrocenyl groups led to the release of the loaded cargos. The present work illustrates a valuable design example of supramolecular Janus systems using the host-guest complexation between β-cyclodextrin and ferrocenyl structures. The present supramolecular micelle may be used as a promising molecular vehicle for application in the field of stimuli-responsive drug delivery.

One-pot synthesis of water-soluble, β-cyclodextrin-based polyrotaxanes in a homogeneous water system and its use in bio-applications.

A small, nano-sized, water-soluble polyrotaxane (PR) was synthesized using a highly efficient one-pot synthesis strategy in a homogeneous water system, formed from β-cyclodextrin-(COOH)2, poly(propylene glycol)bis(2-aminopropyl ether) (PPG, 2 kDa) and a mono-(6-azido-6-desoxy)-β-cyclodextrin stopper via room temperature click chemistry. β-cyclodextrin-(COOH)2 and PR were characterized by one- and two-dimensional NMR as well as by high resolution transmission electron microscopy (HR-TEM). The number of carboxyl groups in one PR was determined by 1H NMR. Two-dimensional diffusion-ordered NMR spectroscopy (2D DOSY) and nuclear Overhauser enhancement spectroscopy (2D NOESY) show that β-cyclodextrin-(COOH)2 and PPG successfully formed an inclusion complex. HR-TEM revealed the morphology of water-soluble PR as a spherical nanoparticle with a size of approximately 3.5 nm ± 1.5 nm. PR was labeled with rhodamine to assess its biocompatibility and cell membrane penetrability in vitro. The in vivo real-time fluorescent imaging biodistribution experiments indicated that water-soluble PR can actively target tumor sites using an enhanced permeability and retention (EPR) effect, with a significantly prolonged blood circulation time in tumor-bearing mice.

Concurrently optimized cooperative pulses in robust quantum control: application to broadband Ramsey-type pulse sequence elements

A general approach is introduced for the efficient simultaneous optimization of pulses that compensate each otherʼs imperfections within the same scan. This is applied to Ramsey-type experiments for a broad range of frequency offsets and scalings of the pulse amplitude, resulting in pulses with significantly shorter duration compared to individually optimized broadband pulses. The advantage of the cooperative pulse approach is demonstrated experimentally for the case of two-dimensional nuclear Overhauser enhancement spectroscopy. In addition to the general approach, a symmetry-adapted analysis of the optimization of Ramsey sequences is presented. Furthermore, the numerical results led to the disovery of a powerful class of pulses with a special symmetry property, which results in excellent performance in Ramsey-type experiments. A significantly different scaling of pulse sequence performance as a function of pulse duration is found for characteristic pulse families, which is explained in terms of the different numbers of available degrees of freedom in the offset dependence of the associated Euler angles.

Dissimilar effects of solubilized p-toluidine on the shape of micelles of differently charged surfactants

In the present study, pH controlled solubilization of p-toluidine (PTD) in micelles of surfactants having dissimilar head group charge is examined. A connection is revealed between viscosity enhancement and locus of solubilized PTD on the micelles of different surfactants viz. dodecyl trimethylammonium bromide (DTAB, cationic), sodium dodecyl sulfate (SDS, anionic) and dodecyl-N,N-dimethyl-3-amino-1-propane sulfonate (DDMPS, zwitterionic), dodecyl-dimethyl amine oxide (DMDAO, cationic–nonionic) and p-tert-octylphenoxy polyethylene (9.5) ether, Triton X-100 (nonionic) was examined by viscosity, dynamic light scattering and 2D NOESY studies. PTD works as cationic hydrotrope in acidic pH and remains neutral in basic pH. DTAB and DDMPS did not show any significant growth with solubilized p-toluidine, while pH dependant micellar growth/transitions were observed for SDS, DMDAO and TX-100. Dissimilar effects were observed for different surfactants; DMDAO micelles showed maximum growth at pH ∼5.0–6.0 with almost no effect in more acidic pH, SDS micelles grew only in acidic conditions, while Triton X-100 micelles grew more in basic media. The effect of temperature on DMDAO and Triton X-100 micelles in the presence of PTD was also examined. The location of PTD in micelle was obtained from two-dimensional nuclear Overhauser enhancement spectroscopy (2D-NOESY).

NMR Analysis of a Kinetically Trapped Intermediate of a Disulfide-Deficient Mutant of the Starch-Binding Domain of Glucoamylase

A thermally unfolded disulfide-deficient mutant of the starch-binding domain of glucoamylase refolds into a kinetically trapped metastable intermediate when subjected to a rapid lowering of temperature. We attempted to characterise this intermediate using multidimensional NMR spectroscopy. The 1H–15N heteronuclear single quantum coherence spectrum after a rapid temperature decrease (the spectrum of the intermediate) showed good chemical shift dispersion but was significantly different from that of the native state, suggesting that the intermediate adopts a nonnative but well-structured conformation. Large chemical shift changes for the backbone amide protons between the native and the intermediate states were observed for residues in the β-sheet consisting of strands 2, 3, 5, 6, and 7 as well as in the C-terminal region. These residues were found to be in close proximity to aromatic residues, suggesting that the chemical shift changes are mainly due to ring current shifts caused by the aromatic residues. The two-dimensional nuclear Overhauser enhancement (NOE) spectroscopy experiments showed that the intermediate contained substantial, native-like NOE connectivities, although there were fewer cross peaks in the spectrum of the intermediate compared with that of the native state. It was also shown that there were native-like interresidue NOEs for residues buried in the protein, whereas many of the NOE cross peaks were lost for the residues involved in a surface-exposed aromatic cluster. These results suggest that, in the intermediate, the aromatic cluster at the surface is structurally less organised, whereas the interior of the protein has relatively rigid, native-like side-chain packing.

Micellization of a cationic gemini surfactant in aqueous solutions with different alkanols and alkanediols as additives: Effect of nonpolar chain and position of hydroxyl groups

The gemini surfactant N-N′bis(dimethyldodecyl)-1,4-butanediammonium dibromide (12-4-12) was synthesized and its critical micelle concentrations (CMCs) and degree of counterion dissociation ( α) in aqueous solutions in the presence of alkanols viz ethanol, isomeric butyl alcohols, 1-hexanol and alkanediols (ethanediol, 1,4-butanediol, 1,2-hexanediol, 2,5-hexanediol 1,6-hexanediol, and 1,8-octanediol) determined from electrical conductivity are reported. While ethanol, ethanediol, 1,4-butanediol showed an increase in CMC, a decrease was seen for isomeric butyl alcohols, 1-hexanol, isomeric hexanediols and 1,8-octanediol. For butyl alcohols the CMC decrease showed the trend 1° >2° > 3°; in C 6 diols, 1,2-hexanediol exerted more decrease as compared to 2,5-hexanediol and 1,6-hexanediol.The results are explained on the basis of the structure and hydrophobicity of alcohols that determine their effect as cosolvent or cosurfactant (partitioning in micelles). Two-dimensional nuclear overhauser enhancement spectroscopy (2D-NOESY) was used to examine the location for 1-butanol and 1,4-butanediol in micellar systems as representative additives from alkanols and alkanediols showing CMC decreasing and increasing effect respectively.

1H NMR Spectroscopic Investigations on the Conformation of Amphiphilic Aromatic Amino Acid Derivatives in Solution: Effect of Chemical Architecture of Amphiphiles and Polarity of Solvent Medium

In this study, the conformation of the amphiphilic lauryl esters of L-tyrosine (LET) and L-phenylalanine (LEP) in water and dimethyl sulfoxide is established. The alkyl chain protons of LEP in D(2)O appear at δ 1.010-1.398 and show an upfield shift and large line width, suggesting the proximity of the phenyl ring to the alkyl chain in contrast to that of LET. Quite interestingly, in DMSO-d(6), the (1)H NMR spectra of LET and LEP show a strong similarity that is suggestive of an orientation that positions the aromatic ring and aliphatic chain away from each other. These results are substantiated with two-dimensional nuclear Overhauser enhancement spectroscopy (2D NOSEY). Theoretical molecular models of the conformation at the interface corroborate the experimental findings. Investigations of the solvent polarity and chemical structure-dependent conformation are discussed.

PSEUDO-DEWETTING BEHAVIOR OF LOW MOLECULAR WEIGHT POLY(ETHYLENE OXIDE) MELTS ON MICA SURFACE

Micellization of a series of newly synthesized dialkyl benzene sulfonates was studied using proton chemical shift changes, spin-lattice, and spin-spin relaxation NMR spectroscopy, and two-dimensional nuclear Overhauser enhancement spectroscopy (2D NOESY). The o-substituted chains are normal alkyl chains with varying lengths, and the m-substituted ones are branched alkyl chains. The results showed that the longer the o-substituted normal alkyl chain, protons of more methylene groups participated in the formation of the rigid surface layer of the hydrophobic micellar core. Consequently, the larger was the area per molecule adsorbed on the interface between oil and water at saturation. The branched m-substituted alkyl chains of the dialkyl benzene sulfonates were less tightly packed than the o-substituted normal alkyl chains in the hydrophobic micellar cores. The shorter the m-substituted branched alkyl chains, the looser they were packed in the hydrophobic micellar core. The relative arrangement of the surfactant molecules in the micelles was elucidated.

Stacking Structure of Confined 1‐Butanol in SBA‐15 Investigated by Solid‐State NMR Spectroscopy

Understanding the complex thermodynamic behavior of confined amphiphilic molecules in biological or mesoporous hosts requires detailed knowledge of the stacking structures. Here, we present detailed solid-state NMR spectroscopic investigations on 1-butanol molecules confined in the hydrophilic mesoporous SBA-15 host. A range of NMR spectroscopic measurements comprising of (1)H spin-lattice (T(1)), spin-spin (T(2)) relaxation, (13)C cross-polarization (CP), and (1)H,(1)H two-dimensional nuclear Overhauser enhancement spectroscopy ((1)H,(1)H 2D NOESY) with the magic angle spinning (MAS) technique as well as static wide-line (2)H NMR spectra have been used to investigate the dynamics and to observe the stacking structure of confined 1-butanol in SBA-15. The results suggest that not only the molecular reorientation but also the exchange motions of confined molecules of 1-butanol are extremely restricted in the confined space of the SBA-15 pores. The dynamics of the confined molecules of 1-butanol imply that the (1)H,(1)H 2D NOESY should be an appropriate technique to observe the stacking structure of confined amphiphilc molecules. This study is the first to observe that a significant part of confined 1-butanol molecules are orientated as tilted bilayered structures on the surface of the host SBA-15 pores in a time-average state by solid-state NMR spectroscopy with the (1)H,(1)H 2D NOESY technique.

Thermodynamics of Mixed Micellization of Isomeric Hexanediols in Sodium Dodecyl Sulfate

The thermodynamic parameters of mixed micelle formation (Δ mic G°, Δ mic H°, Δ mic S°) have been determined for a series of mixed micelles consisting of two isomeric hexanediols (1,2-hexanediol and 1,6-hexanediol) in sodium dodecylsulfate micellar solutions. The enthalpies of micellization were determined directly from isoperibol solution calorimetry. Gibbs energies and entropies of micelle formation were obtained from the application of the charged pseudo-phase model of micelle formation to the calorimetric critical micelle concentration values. The location of the alcohols in the micellar palisade layer has been determined from two-dimensional nuclear Overhauser enhancement spectroscopy (NOESY) experiments. The calorimetric titration data indicates that the placement of the hydroxyl groups on the six carbon backbone greatly affects the energetics of the micelle formation process. From the NMR data, the location of the cosurfactant in the micelle has been determined. These results indicate that the locus of solubilization affects the subtle balance of forces responsible for the formation of the mixed aggregates.

Aggregation Behavior of Quaternary Ammonium Dimeric Surfactant C 14-s-C 14·2Br Micelles

The aggregation behavior of gemini surfactants 14-s-14 micelles in heavy water solutions was studied using 1H NMR relaxation and two-dimensional nuclear Overhauser enhancement spectroscopy (2D NOESY). Spin-lattice and spin-spin relaxation measurements of the protons showed that the motion of the spacer protons and a part of the methylene protons next to the polar head group was seriously restricted. Therefore, these protons should be involved in the formation of the surface layer of the hydrophobic micellar core. The hydrophobic protons that were away from the polar head group were situated internally in the micellar core and moved relatively freely. Relaxation measurements of the 14-s-14 series (s=2, 3, 4) also showed that the molecules were more tightly packed as the length of the spacer decreased. Their motion was relatively more restricted than those of TTAB, the monomeric homologue of 14-4-14. 2D NOESY spectrum of 14-4-14 exhibited the same pattern as that of 16-4-16. This showed that the micelles of 14-4-14 were spherical, and the surface exhibited a saw-toothed form, similar to that of 16-4-16. Consequently, the length of the alkyl chain did not have any effect on the relative arrangement of molecules in the micelles.

1D and 2D NMR investigations of the micelle-formation process in 8-phenyloctanoate micelles

The micellization process of sodium 8-phenyloctanoate in a deuterated aqueous solution was studied, using 1H NMR spectroscopy and two-dimensional (2D) nuclear Overhauser enhancement spectroscopy (NOESY). 1H NMR spectra, acquired for the sodium 8-phenyloctanoate before and after the critical micelle concentration (CMC) value, showed that large chemical-shift changes were observed for both the aromatic proton peaks and the peaks for the methylene protons near the terminal phenyl group. The plots for the methylene protons near the headgroup do not show these large chemical-shift changes. These observations support the view that the terminal phenyl ring of the surfactant is primarily located in the micellar interior. The 2D NOESY experiments show significant cross-peaks, between the phenyl protons and the methylene protons of the surfactant, that substantiate the conclusions on those drawn from NMR aromatic solute induced shift (ASIS) experiments on the same and similar systems. All these observations are consistent with the Gruen model of the micelle and previous NMR NOESY experiments for other surfactant systems.Key words: surfactants, micelles, NMR, NOESY.

Microstructures of 2,5-dialkyl benzene sulfonate micelles studied using 1H NMR

Micellization of a series of newly synthesized dialkyl benzene sulfonates was studied using proton chemical shift changes, spin-lattice and spin-spin relaxation NMR spectroscopy, and two-dimensional nuclear Overhauser enhancement spectroscopy (2D NOESY). The o-substituted chains are normal alkyl chains with varying lengths, and the m-substituted ones are branched alkyl chains. The results showed that the longer the o-substituted normal alkyl chain, the more the methylene groups participated in the formation of the rigid surface layers of the hydrophobic micellar cores. Consequently, the larger was the area per molecule adsorbed on the interface between oil and water at saturation. The branched m-substituted alkyl chains of the dialkyl benzene sulfonates were less tightly packed than the o-substituted normal alkyl chains in the hydrophobic micellar cores. The shorter the m-substituted branched alkyl chains, the looser they were packed in the hydrophobic micellar cores. The relative arrangement of the surfactant molecules in the micelles was elucidated.

On the use of simulated annealing to automatically assign decorrelated components in second-order blind source separation

In this paper, an automatic assignment tool, called BSS-AutoAssign, for artifact-related decorrelated components within a second-order blind source separation (BSS) is presented. The latter is based on the recently proposed algorithm dAMUSE, which provides an elegant solution to both the BSS and the denoising problem simultaneously. BSS-AutoAssign uses a local principal component analysis (PCA)to approximate the artifact signal and defines a suitable cost function which is optimized using simulated annealing. The algorithms dAMUSE plus BSS-AutoAssign are illustrated by applying them to the separation of water artifacts from two-dimensional nuclear overhauser enhancement (2-D NOESY) spectroscopy signals of proteins dissolved in water.

Solution Structure of the Human Immunodeficiency Virus Type 1 p6 Protein

The human immunodeficiency virus type 1 p6 protein represents a docking site for several cellular and viral binding factors and fulfills major roles in the formation of infectious viruses. To date, however, the structure of this 52-amino acid protein, by far the smallest lentiviral protein known, either in its mature form as free p6 or as the C-terminal part of the Pr55 Gag polyprotein has not been unraveled. We have explored the high resolution structure and folding of p6 by CD and NMR spectroscopy. Under membranous solution conditions, p6 can adopt a helix-flexible helix structure; a short helix-1 (amino acids 14-18) is connected to a pronounced helix-2 (amino acids 33-44) by a flexible hinge region. Thus, p6 can be subdivided into two distinct structural and functional domains; helix-2 perfectly defines the region that binds to the virus budding factor AIP-1/ALIX, indicating that this structure is required for interaction with the endosomal sorting complex required for transport. The PTAP motif at the N terminus, comprising the primary late assembly domain, which is crucial for interaction with another cellular budding factor, Tsg101, does not exhibit secondary structure. However, the adjacent helix-1 may play an indirect role in the specific complex formation between p6 and the binding groove in Tsg101. Moreover, binding studies by NMR demonstrate that helix-2, which also comprises the LXXLF motif required for incorporation of the human immunodeficiency virus type 1 accessory protein Vpr into budding virions, specifically interacts with the Vpr binding region, indicating that under the specific solution conditions used for structure analysis, p6 adopted a functional conformation.

NMR structures of anti-HIV d-peptides derived from the N-terminus of viral chemokine vMIP-II

The viral macrophage inflammatory protein-II (vMIP-II) encoded by Kaposi’s sarcoma-associated herpesvirus has unique biological activities in that it blocks the cell entry by several different human immunodeficiency virus type 1 (HIV-1) strains via chemokine receptors including CXCR4 and CCR5. In this paper, we report the solution structure of all- d-amino acid peptides derived from the N-terminus of vMIP-II, which have been shown to have strong CXCR4 binding activity and potently inhibit HIV-1 entry via CXCR4, by using long mixing time two-dimensional nuclear Overhauser enhancement spectroscopy experiments. Both of all- d-peptides vMIP-II (1–10) and vMIP-II (1–21), which are designated as DV3 and DV1, respectively, have higher CXCR4 binding ability than their l-peptide counterparts. They are partially structured in aqueous solution, displaying a turn-like structure over residues 5–8. The small temperature coefficients of His-6 amide proton for both peptides also suggest the formation of a small hydrophobic pocket centered on His-6. The structural features of DV3 are very similar to the reported solution structure of all- l-peptide vMIP-II (1–10) [M.P. Crump, E. Elisseeva, J. Gong, I. Clark-Lewis, B.D. Sykes, Structure/function of human herpesvirus-8 MIP-II (1–71) and the antagonist N-terminal segment (1–10), FEBS Lett. 489 (2001) 171], which is consistent with the notion that d- and l-enantiomeric peptides can adopt mirror image conformations. The NMR structures of the d-peptides provide a structural basis to understand their mechanism of action and design new peptidomimetic analogs to further explore the structure–activity relationship of d-peptide ligand binding to CXCR4.