Micellar Environment Research Articles

Use of green RPLC methods as an alternative to conventional RPLC methods in the determination of the pKa values of some H2 receptor antagonists

In this study, the chromatographic retention behavior and dissociation constants (pKa ) of H2 receptor antagonists ranitidine and famotidine were determined by the green reverse phase liquid chromatography (RPLC) and hybrid micellar chromatography methods, which are widely used today. Replicate analyses were performed on a Gemini NX C18 (250 × 3.0 mm ID, 5 μm) column at constant temperature (37 °C) and flow rate (1 mL/min). The obtained data analyses were evaluated with the linear solvation energy relationship (LSER) approach and the consistency of the data was assessed by calculating the theoretical retention time values. The pK a 1 s s and pK a 2 s s values obtained in ethanol–water binary mixtures containing 11%, 13%, 15%, and 20% (v/v) ethanol were also calculated with this approach. The pKa values of these compounds in water and pure micellar environment were calculated with pK a s s values and solvent. It was observed that the p K a w w data obtained by three different methods were compatible. Accordingly, with the hybrid micelles method, p K a 2 w w and p K a 3 w w values for famotidine were calculated as 7.305 and 9.869, respectively, and p K a 1 w w and p K a 2 w w values for ranitidine were calculated as 2.952 and 8.589. The environmental impacts of the methods applied in the study were evaluated using green metric tools.

Towards antimicrobial agents: Design and antibacterial activity of a hybrid fluorophore where porphyrin and Rose Bengal moieties are linked through the hydroxyl group of a xanthene dye

The axial complex of Sn(IV)-tetra(4-sulfophenyl)porphyrin (SnP) with Rose Bengal (RB) was obtained where RB axial binding is realized through the hydroxyl groups of the xanthene dye [SnP(RB)2]. The luminescent properties of the SnP(RB)2 (fluorescence and ability to generate singlet oxygen at room temperature) in aqueous media with additives of surfactant cetylpyridinium chloride (CPC) and ε-poly-l-lysine (EPL) were studied. It was found that nature of the medium (surfactant additives of different concentrations) determines the effectiveness of the photoinduced energy transfer from the RB fragment to the SnP fragment of the hybrid fluorophore (HF). It has been established that the ability of the HF to generate singlet oxygen in D2O and D2O-micellar media is higher than that of its constituent fragments. The dark and photodynamic antibacterial activity of the HF against two microorganisms [Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus)] was determined and analyzed. It was shown how the antibacterial activity of the HF depends on the nature of the bacteria, the micellar environment and radiation dose.

Mild and Effective Method for the Nickel-Catalyzed Arylation of Glycosyl Thiols in Aqueous Surfactant Solution.

Aryl thioglycosides have broad applicability as both glycosyl donors and glycomimetic compounds. Their synthesis via the cross-coupling of glycosyl thiols with aryl halides has become a popular method for their construction because it allows better selectivity for anomeric configuration as well as a wider functional group tolerance compared to traditional methods. Herein, we report a nickel-catalyzed method for the synthesis of aryl thioglycosides which utilizes an aqueous micellar environment as the reaction medium. This alternative method allows for mild conditions while circumventing expensive palladium, leading to the successful synthesis of over 30 aryl thioglycosides, including challenging 1,2-cis thioglycoside products.

Kinetic and Mechanistic Investigation of L‐Phenylalanine Oxidation by Alkaline Cu(III) Periodate in CPC Micellar Medium

ABSTRACTAmino acid oxidation is fascinating because different oxidants produce diverse compounds. No research has examined how metal catalysts affect amino acid oxidation by diperiodatocuprate (III) (DPC) in micellar environments. This research is crucial to understanding amino acids in redox processes and identifying active species of Ru(III) and DPC. The study will evaluate how cationic surfactant affects Ru(III)‐facilitated L‐phenylalanine (L‐Pheala) oxidation utilizing DPC in an alkaline medium. The reaction's advancement has been assessed employing the pseudo‐first‐order condition as a gauge for [OH−], [DPC], ionic strength, [L‐Pheala], [Ru(III)], [IO4−], [Surfactant], and temperature. L‐Pheala and DPC interact stoichiometrically in a ratio of 1:4. Across the spectrum of concentrations examined, the reported reaction reflects less than unit order kinematics in relation to both [L‐Pheala] (0.61 in the aqueous medium and 0.58 in the CPC micellar medium) and [OH−] (0.47 in the aqueous medium and 0.51 in the CPC micellar medium), first‐order reliance on the [DPC] and [Ru(III)], and negative fractional‐order for [IO4−] (−0.54 in the aqueous medium and −0.56 in the CPC micellar medium). A zero salt effect is suggested by the observed constancy in oxidation rate with the inclusion of electrolytes. The oxidation rate is significantly enhanced by Ru(III) solution (as a catalyst) at ppm concentration. Cetylpyridinium chloride (CPC) micellar media facilitate an additional enhancement (four times) in the rate of the reaction. CPC thus exhibits an excellent compatibility with Ru(III) for the L‐Pheala oxidation using (DPC).

Unveiling the role of solubilization of metformin hydrochloride assimilated in nonionic surfactants mediated mixed micellar assemblies

This study examines the distribution of an antidiabetic drug metformin hydrochloride (MNH) between water and mixed micellar environments produced by nonionic surfactants Tween 80 (TW-80) and Triton X-100 (TX-100). In our research, we described the UV–visible absorption spectra of a drug at various surfactant concentrations above and below critical micelle concentration (CMC). When employing TX-100, the absorbance spectra appeared to shift towards shorter wavelengths (blue shift) and there was an increase in absorbance intensity (hyperchromic shift), while using Tween 80, absorbance intensity increased (hyperchromic shift). We estimated the partition coefficient (Kx) from differential absorption data and utilized it to derive the free energy of partition (∆Gp). The partition coefficient in a single micellar system was found to be 7.82×106 and 1.79×106 in the presence of TW-80 and TX-100, respectively. The partition coefficient for the MNH/TW-80 system in a mixed micellar system reaches its maximum value of 1.08×107 when TX-100 is present at 1.26×106 M, indicating a considerable increase in the solubilizing power of micelles. The results showed that mixed micelles of TX-100/TW-80 were more effective for the solubilization of MNH than their individual micelles. It was crystal clear from the negative values of ∆Gb that binding is also spontaneous.

Active Site Environment and Reactivity of Copper-Aβ in Membrane Mimetic SDS Micellar Environment.

Alzheimer's disease (AD) is characterized by the abnormal aggregation of amyloid β (Aβ) peptide in extracellular deposits generated upon proteolysis of Amyloid Precursor Protein (APP). While copper (Cu(II)) binds to Aβ in soluble oligomeric and aggregated forms, its interaction with membrane-bound Aβ remains elusive. Investigating these interactions is crucial for understanding AD pathogenesis. Here, utilizing SDS micelles as a simplified membrane mimic, we focus on elucidating the interplay between membrane-anchored Aβ and copper, given their pivotal roles in AD. We employed spectroscopic techniques including UV, CD, and EPR to characterize the active site of Cu-Aβ complexes. Our findings demonstrate that copper interacts with Aβ peptides in membrane-mimicking micellar environments similarly to aqueous buffer solutions. Cu-Aβ complexes in this medium also induce higher hydrogen peroxide (H2O2) production, potentially contributing to AD-related oxidative stress. Moreover, we observe an increased oxidation rate of neurotransmitter such as dopamine by Cu-Aβ complexes. These results enhance our understanding of Cu-Aβ interactions in AD pathology and offer insights into potential therapeutic interventions targeting this interaction.

Photophysical Response of Propranolol in Biomimetic Micellar Media of Alkyltrimethylammonium Bromide Surfactants: Effect of pH and Alkyl Chain Length.

The photophysical behavior of a β-blocker drug propranolol (PPL) in micellar environments, formed by alkyltrimethylammonium bromide surfactants viz.; Cetyltrimethylammonium bromide (CTAB), Tetradecyltrimethylammonium bromide (TTAB), and Dodecyltrimethylammonium bromide (DTAB), has been investigated through fluorescence and UV-visible spectroscopic techniques at pH levels of 3.5, 7.4, and 10.4. The impact of pH on the critical micelle concentration (cmc) and micropolarity of micelles were assessed using pyrene as a photophysical probe. The cmc values were found to be lower at pH 10.4 compared to pH 7.4 and pH 3.5. Fluorescence emission intensities of PPL at 323nm, 338nm, and 352nm were significantly influenced by pH, hydrophobic alkyl chain length of surfactants, and their concentrations. Quenching experiments with Cetylpyridinium chloride (CpCl) indicated the localization of charged and uncharged forms of PPL within micelles, with quenching constant (Ksv) values dependent on alkyl chain length and pH. At pH < pKa, PPL is positioned near the Stern layer, whereas at pH 10.4, its naphthalene moiety resides near the hydrophobic micellar core. UV spectroscopy showed that the charged form of PPL interacted with micelles only above cmc, while the neutral form interacted even below the cmc. Density Functional Theory (DFT) reveals the HOMO of the surfactants to be localized on the hydrocarbon chains, and the LUMO localized around the quaternary ammonium unit. Upon complexation with PPL, both HOMO and LUMO shifted to the drug, thereby decreasing energy levels. The findings are explained based on weak noncovalent interactions, further supported and analyzed through Reduced Density Gradient (RDG) and Noncovalent Interaction (NCI) methods, confirming synergistic non-covalent interactions in surfactant-PPL complexes.

Thermodynamics of the polymerisation of polyglycerols in an acidic and micellar environment

Thermodynamics of the polymerisation of polyglycerols in an acidic and micellar environment

A novel bioresponsive self-immolative spacer based on aza-quinone methide reactivity for the controlled release of thiols, phenols, amines, sulfonamides or amides.

A stimuli-sensitive linker is one of the indispensable components of prodrugs for cancer therapy as it covalently binds the drug and releases it upon external stimulation at the tumour site. Quinone methide elimination has been widely used as the key transformation to release drugs based on their nucleofugacity. The usual approach is to bind the drug to the linker as a carbamate and release it as a free amine after a self-immolative 1,6-elimination. Although this approach is very efficient, it is limited to amines (as carbamates), alcohols or phenols (as carbonates) or other acidic functional groups. We report here a self-immolative spacer capable of directly linking and releasing amines, phenols, thiols, sulfonamides and carboxyamides after a reductive stimulus. The spacer is based on the structure of (5-nitro-2-pyrrolyl)methanol (NPYM-OH), which was used for the direct alkylation of the functional groups mentioned above. The spacer is metabolically stable and has three indispensable sites for bioconjugation: the bioresponsive trigger, the conjugated 1,6 self-immolative system and a third arm suitable for conjugation with a carrier or other modifiers. Release was achieved by selective reduction of the nitro group over Fe/Pd nanoparticles (NPs) in a micellar aqueous environment (H2O/TPGS-750-M), or by NADH mediated nitroreductase activation. A DFT study demonstrates that, during the 1,6 elimination, the transition state formed from 5-aminopyrrole has a lower activation energy compared to other 5-membered heterocycles or p-aminobenzyl derivatives. The NPYM scaffold was validated by late-stage functionalisation of approved drugs such as celecoxib, colchicine, vorinostat or ciprofloxacin. A hypoxia-activated NPYM-based prodrug (HAP) derived from HDAC inhibitor ST7612AA1 was also produced, which was active in cancer cells under hypoxic conditions.

Main chain selective polymer degradation: controlled by the wavelength and assembly.

The advent of reversible deactivation radical polymerization (RDRP) revolutionized polymer chemistry and paved the way for accessing synthetic polymers with controlled sequences based on vinylic monomers. An inherent limitation of vinylic polymers stems from their all-carbon backbone, which limits both function and degradability. Herein, we report a synthetic strategy utilizing radical ring-opening polymerization (rROP) of complementary photoreactive cyclic monomers in combination with RDRP to embed photoresponsive functionality into desired blocks of polyvinyl polymers. Exploiting different absorbances of photoreactive cyclic monomers, it becomes possible to degrade blocks selectively by irradiation with either UVB or UVA light. Translating such primary structures of polymer sequences into higher order assemblies, the hydrophobicity of the photodegradable monomers allowed for the formation of micelles in water. Upon exposure to light, the nondegradable blocks detached yielding a significant reduction in the micelle hydrodynamic diameter. As a result of the self-assembled micellar environment, telechelic oligomers with photoreactive termini (e.g., coumarin or styrylpyrene) resulting from the photodegradation of polymers in water underwent intermolecular photocycloaddition to photopolymerize, which usually only occurs efficiently at longer wavelengths and a much higher concentration of photoresponsive groups. The reported main chain polymer degradation is thus controlled by the irradiation wavelength and the assembly of the polymers.

Surfactant-induced alterations in optoelectronic properties of perylene diimide dyes: modulating sensing responses in the aqueous environment.

The compartmentalization effect of microheterogeneous systems, like surfactant aggregates, showcases altered optoelectronic properties of a perylene diimide-based chromogenic dye (PDI-Ala) compared to bulk water. The relatively hydrophobic microenvironment, poor hydration, and exceptionally large local concentration of dye molecules in the confined environment affect their interaction with target analytes. This realization intrigued us to investigate if micellization can modify the sensing properties (selectivity, sensitivity, response kinetics, output signal, etc.) of the encapsulated dye molecules in the aqueous medium. Response comparisons of PDI-Ala to the ionic analyte (Fe3+) and biomolecule (heparin) in aqueous and surfactant-bound states highlighted significant variations. Fe3+ interaction exhibited a "turn-off" fluorescence response in a water medium, while surfactant-bound conditions triggered "turn-on" fluorescence, enhancing selectivity at the micelle-water interface. Conversely, the native probe showed no interaction with heparin in water but displayed a turn-on fluorescence response in cetyltrimethylammonium bromide (CTAB) micelles, indicating the transformation of a silent molecule into a turn-on fluorescence sensor. This study underscores the influence of micellar environments on dye molecules, altering the sensing responses and selectivity toward analytes, crucial for applications in understanding cellular pathways and toxicity mechanisms.

Unusual Phase Behaviour for Organo-Halide Perovskite Nanoparticles Synthesized via Reverse Micelle Templating

Micelle templating has emerged as a powerful method to produce monodisperse nanoparticles. Herein, we explore unconventional phase transformations in the synthesis of organo-halide perovskite nanoparticles utilizing reverse micelle templates. We employ diblock-copolymer reverse micelles to fabricate these nanoparticles, which confines ions within micellar nanoreactors, retarding reaction kinetics and facilitating perovskite cage manipulation. The confined micellar environment exerts pressure on both precursors and perovskite crystals formed inside, enabling stable phases not typically observed at room temperature in conventional synthesis. This provides access to perovskite structures that are otherwise challenging to produce. The hydrophobic shell of the micelle also enhances perovskite stability, particularly when combined with anionic exchange approaches or large aromatic cations. This synergy results in long-lasting stable optical properties despite environmental exposure. Reverse micelle templates offer a versatile platform for modulating perovskite structure and behavior across a broad spectrum of perovskite compositions, yielding unique phases with diverse emission characteristics. By manipulating the composition and properties of the reverse micelle template, it is possible to tune the characteristics of the resulting nanoparticles, opening up exciting opportunities for customizing optical properties to suit various applications.

Increasing the aqueous solubility of the anesthetic propofol through wormlike micelle formation

Propofol, a phenol derivative, is commonly employed as an intravenous anesthetic during clinical procedures, formulated as an oil/water emulsion due to its poor solubility in water. The stability limitations associated with emulsions have prompted research efforts towards developing aqueous formulations of propofol. In this work, we investigate the solubility enhancement of propofol in anionic and cationic surfactants. Our findings reveal that the solubility of propofol can increase significantly, up to 100-fold, depending on the nature of the micellar aggregate, as observed for alkylammonium halogenates CnTAB (for n = 12, 14 and 16), contrasting with the lower solubility with SDS. Interestingly, C14TAB and C16TAB demonstrate significantly higher solubility than C12TAB. This was attributed to the formation of wormlike micelles, in which the propofol molecules are positioned between the cationic heads of the surfactant molecules, changing the micellar curvature and the morphology of the aggregate. Therefore, the aromatic molecules in the micellar environment can be partitioned into the micellar cores and their palisades. Regarding C12TAB, the alkyl chain is too short to form wormlike micelles, thus, concentrating propofol molecules mainly into the micellar core, and consequently, leading to their aggregation. Solubility diagrams of propofol were constructed in conjunction with different surfactants. The systems exhibiting viscoelastic behavior, indicative of wormlike micelle formation, were further investigated using rheology. Additionally, the fluorescent properties of propofol enabled the examination of the anesthetic molecule within diverse micellar environments.

Structural dynamics influences the antibacterial activity of a cell-penetrating peptide (KFF)3K

Given the widespread demand for novel antibacterial agents, we modified a cell-penetrating peptide (KFF)3K to transform it into an antibacterial peptide. Namely, we inserted a hydrocarbon staple into the (KFF)3K sequence to induce and stabilize its membrane-active secondary structure. The staples were introduced at two positions, (KFF)3K[5–9] and (KFF)3K[2–6], to retain the initial amphipathic character of the unstapled peptide. The stapled analogues are protease resistant contrary to (KFF)3K; 90% of the stapled (KFF)3K[5–9] peptide remained undigested after incubation in chymotrypsin solution. The stapled peptides showed antibacterial activity (with minimal inhibitory concentrations in the range of 2–16 µM) against various Gram-positive and Gram-negative strains, contrary to unmodified (KFF)3K, which had no antibacterial effect against any strain at concentrations up to 32 µM. Also, both stapled peptides adopted an α-helical structure in the buffer and micellar environment, contrary to a mostly undefined structure of the unstapled (KFF)3K in the buffer. We found that the antibacterial activity of (KFF)3K analogues is related to their disruptive effect on cell membranes and we showed that by stapling this cell-penetrating peptide, we can induce its antibacterial character.

Surfactant-Assisted Synthesis of Bismuth Oxychloride Nanoflowers for Electrochemical Sensing of Heavy Metal Ions

Heavy metal ion contamination of drinking water is a significant, invisible threat to public health which requires active and decentralized monitoring with high sensitivity, accuracy and reliability. The government and regulatory agencies actively survey and maintain established limits on heavy metal contamination, but generally prioritizing localized hotspots in high-risk communities. Their characterization techniques are typically expensive and inaccessible to the public, requiring specialized training and extended sample shipping times, with a purview restricted to public infrastructure. As plumbing systems corrode and contaminants leach into drinking water systems, independent means of oversight are becoming increasingly vital in effectively identifying and mitigating toxic exposure. In this work we propose the development and application of a high surface area bismuth oxychloride nanoflower for the electrochemical detection of zinc and lead ions in drinking water. The flower structure was synthesized via hydrolysis of bismuth chloride salt in a micellar environment of sodium dodecyl sulfate, followed by aqueous chemical reduction and transformation to metallic bismuth. The size and uniformity of the synthesized nanoflower was characterized with scanning electron microscopy (SEM), and the composition and microstructure were investigated using energy dispersive x-ray spectroscopy (EDS) analysis and x-ray diffraction (XRD). The nanoflowers were deposited onto a glassy carbon electrode and coated with a protective Nafion layer, prior to cyclic voltammetry analysis of analyte ion reactivity, achieving detection of lead and zinc ions in buffer and practical drinking water samples. These results indicate the viability of bismuth-based nanoflower structures for portable, accessible detection of heavy metal ions, with enhanced sensitivity.

Heme-Aβ in SDS micellar environment: Active site environment and reactivity

Alzheimer's disease (AD), the most common cause of dementia, is a progressive neurodegenerative disorder that causes brain cell death. Oxidative stress derived from the accumulation of redox cofactors like heme in amyloid plaques originating from amyloid β (Aβ) peptides has been implicated in the pathogenesis of AD. In the past our group has studied the interactions and reactivities of heme with soluble oligomeric and aggregated forms of Aβ. In this manuscript we report the interaction of heme with Aβ that remains membrane bound using membrane mimetic SDS (sodium dodecyl sulfate) micellar medium. Employing different spectroscopic techniques viz. circular dichroism (CD), absorption (UV–Vis), electron paramagnetic resonance (EPR) and resonance Raman (rR) we find that Aβ binds heme using one of its three His (preferentially His13) in SDS micellar medium. We also find that Arg5 is an essential distal residue responsible for higher peroxidase activity of heme bound Aβ in this membrane mimetic environment than free heme. This peroxidase activity exerted by even membrane bound heme-Aβ can potentially be more detrimental as the active site remains close to membranes and can hence oxidise the lipid bilayer of the neuronal cell, which can induce cell apoptosis. Thus, heme-Aβ in solution as well as in membrane-bound form are detrimental.

Dye-surfactant interaction in aqueous premicellar and micellar environments in the alkaline fading of di-positive methyl green carbocation

The alkaline fading of di-positive methyl green carbocation (MeG2+) has been studied in different aqueous premicellar and micellar environments of anionic, cationic as well as non-ionic surfactants. Mono- and di-negative anions like halides and sulphate have been found to show an inhibiting effect on the fading reaction owing to the formation of dye-anion ion-pair adduct before hydrolysis. The binding strength of the dye-anion ion-pair adduct is in the order: SO42- > I- > Br- > Cl- which rationalizes the same order of inhibition of the rate. A substantial change in the electronic spectra of MeG2+ in the presence of anionic surfactants, sodium dodecyl sulfate (SDS) and dioctyl sodium sulfosuccinate (AOT), in the pre-CMC region indicates a change in the equilibrium distribution of the two stereo isomers of the dye owing to the formation of MeG2+-surfactant ion-pair and ion-pair micelle. The premicellar rate inhibition of the fading reaction by SDS and AOT occurs due to the formation of 1:1 MeG2+-surfactant ion-pair (where ≥ 85 % of MeG2+ remain associated) through electrostatic interaction before hydrolysis. The cationic surfactant cetyltrimethylammonium bromide (CTAB) shows a retarding effect in the post-micellar region as the HO- ion experiences both electrostatic repulsion and steric hindrance to approach the carbocation centre of the dye, embedded in the micelle. The polar hydroxyl group and the polyoxyethylene groups present in the moiety of the non-ionic surfactant Brij35 assist to increase the local concentration of HO- and MeG2+ in the palisade layer resulting in a catalyzing effect on the fading reaction in the post CMC region. Both pre- and post-micellar rate effects have been analyzed quantitatively by different established kinetic models. Detailed calculations have been made to find out different enthalpy and entropy of activation as well as of binding in order to establish the nature of interactions between the dye MeG2+ and monomeric surfactant(s) /micelles as well as solvent molecules. Results of spectrophotometric and tensiometric investigations strongly support the existence of different molecular interactions in different stages of the hydrolysis reaction in the presence of surfactants.

Effectiveness of the hydrophobic core of pyridine tethered N-acyl glycine micelles in improving chromenoquinoline synthesis in water

The organic transformations in water are considered a safe, non-toxic, economical, and eco-friendly alternative. A new series of amphiphile, N-acyl-N-(pyridin-2-ylmethyl)glycine (PyNAG) with variable hydrophobicity was successfully synthesized from glycine. The self-assembly properties were characterized by critical micellar concentration (CMC), aggregation number (Nagg), and diameter (DH). The PyNAG with N- stearoyl moiety showed lower CMC, higher Nagg, and larger DH compared to PyNAG with N- lauryl moiety. Molecular dynamics simulation reveals that the micelle structure is compact and non-bonded energy contribution arises from electrostatic, and van der Walls forces contribute to perfect packing and micelle formation. The ability of the PyNAG micelles to execute important organic transformations in water was demonstrated through synthesizing chromenoquinoline via the Povarov reaction. Micelles with varying diameters were used to conduct the Povarov reaction in order to better understand the functions of the hydrophobicity core of the micellar environment in organic reactions. The results reveal that the Povarov reaction produces a good yield in N-stearoyl-N-(pyridin-2-ylmethyl)glycine (PyN18G) micelles, better than organic solvent and commercial surfactant. Moreover, a linear correlation between the yield and the hydrophobicity of the PyNAG was observed. The findings demonstrate that the micellar interior significantly affects the reactivity of the substrate, which should be taken into consideration while creating new media for metal-catalyzed green synthesis.

Folding and modulation of the helical conformation of Glycophorin A by point mutations.

Transmembrane helix folding and self-association play important roles in biological signaling and transportation pathways across biomembranes. With molecular simulations, studies to explore the structural biochemistry of this process have been limited to focusing on individual fragments of this process - either helix formation or dimerization. While at an atomistic resolution, it can be prohibitive to access long spatio-temporal scales, at the coarse grained (CG) level, current methods either employ additional constraints to prevent spontaneous unfolding or have a low resolution on sidechain beads that restricts the study of dimer disruption caused by mutations. To address these research gaps, in this work, we apply our recent, in-house developed CG model (ProMPT) to study the folding and dimerization of Glycophorin A (GpA) and its mutants in the presence of Dodecyl-phosphocholine (DPC) micelles. Our results first validate the two-stage model that folding and dimerization are independent events for transmembrane helices and found a positive correlation between helix folding and DPC-peptide contacts. The wild type (WT) GpA is observed to be a right-handed dimer with specific GxxxG contacts, which agrees with experimental findings. Specific point mutations reveal several features responsible for the structural stability of GpA. While the T87L mutant forms anti-parallel dimers due to an absence of T87 interhelical hydrogen bonds, a slight loss in helicity and a hinge-like feature at the GxxxG region develops for the G79L mutant. We note that the local changes in the hydrophobic environment, affected by the point mutation, contribute to the development of this helical bend. This work presents a holistic overview of the structural stability of GpA in a micellar environment, while taking secondary structural fluctuations into account. Moreover, it presents opportunities for applications of computationally efficient CG models to study conformational alterations of transmembrane proteins that have physiological relevance.

A micelle-mediated approach enables facile access to bridged oxabicyclo[n.3.1]alkene scaffolds.

Oxabicyclo[n.3.1]alkene scaffolds present in a diverse range of complex natural products have been accessed by reacting 2-cycloalkenones with 1,3-cycloalkadiones in a micellar medium. This reaction occurring in a micellar confinement environment operates through a Michael addition/enolization/oxygen addition cascade to furnish highly functionalized constructs using a sustainable organic synthesis protocol. NMR analysis confirms that the locus of the solubilizates is within the palisade and stern regions of the micellar cavity.