Molecular Dynamics Simulations of Depth Distribution of Spin-Labeled Phospholipids within Lipid Bilayer

Spin-labeled lipids are commonly used as fluorescence quenchers in studies of membrane penetration of dye-labeled proteins and peptides using depth-dependent quenching. Accurate calculations of depth of the fluorophore rely on the use of several spin labels placed in the membrane at various positions. The depth of the quenchers (spin probes) has to be determined independently; however, experimental determination of transverse distributions of spin probe depths is difficult. In this Article, we use molecular dynamics (MD) simulations to study the membrane behavior and depth distributions of spin-labeled phospholipids in a 1-palmitoyl-2-oleoyl-<i>sn</i>-glycero-3-phosphocholine (POPC) bilayer. To probe different depths within the bilayer, a series containing five Doxyl-labeled lipids (<i>n</i>-Doxyl PC) has been studied, in which a spin moiety was covalently attached to <i>n</i>th carbon atoms (where <i>n</i> = 5, 7, 10, 12, and 14) of the <i>sn</i>-2 stearoyl chain of the host phospholipid. Our results demonstrate that the chain-attached spin labels are broadly distributed across the model membrane and their environment is characterized by a high degree of mobility and structural heterogeneity. Despite the high thermal disorder, the depth distributions of the Doxyl labels were found to correlate well with their attachment positions, indicating that the distribution of the spin label within the model membrane is dictated by the depth of the <i>n</i>th lipid carbon atom and not by intrinsic properties of the label. In contrast, a much broader and heterogeneous distribution was observed for a headgroup-attached Tempo spin label of Tempo-PC lipids. MD simulations reveal that, due to the hydrophobic nature, a Tempo moiety favors partitioning from the headgroup region deeper into the membrane. Depending on the concentration of Tempo-PC lipids, the probable depth of the Tempo moiety could span a range from 14.4 to 18.2 Å from the membrane center. Comparison of the MD-estimated immersion depths of Tempo and <i>n</i>-Doxyl labels with their suggested experimental depth positions allows us to review critically the possible sources of error in depth-dependent fluorescence quenching studies

Atomistic Simulations of Coating of Silver Nanoparticles with Poly(vinylpyrrolidone) Oligomers: Effect of Oligomer Chain Length

Silver nanoparticles (AgNPs) possess unique physicochemical properties, which are different from those of matter of the same chemical composition on a larger scale. These features open up the opportunity for their use in many promising chemical and biomedical applications. In this study we have developed an atomistic model for molecular dynamics (MD) simulations of AgNP coated by poly­(<i>N</i>-vinyl-2-pyrrolidone) (PVP) oligomers. We focus on identifying the relative length of PVP oligomers, enabling effective protecting of a crystalline silver core of 4.5 nm diameter from water contacts. Three different PVP-coated AgNP systems have been compared: (i) a nanoparticle coated by a mixture of short-chain PVP oligomers of the varying size and (ii,iii) the silver core wrapped by a single, long-chain PVP polymer with the number of monomers equal to 816 and 1440, respectively. We have validated the MD models of the PVP–AgNPs using a series of MD simulations reproducing adsorption, wrapping, and coating of PVP around a silver core either as short PVP oligomers or as a single-chain, long polymer of a varying length. Our simulations predict that the saturated coating of PVP around the silver core of the given diameter can occur when the polymer chain length approaches 2600–2800 units

Excited-State Dynamics of an Environment-Sensitive Push–Pull Diketopyrrolopyrrole: Major Differences between the Bulk Solution Phase and the Dodecane/Water Interface

The excited-state dynamics of a diketopyrrolopyrrole (DPP) derivative with push–pull substituents has been investigated in a variety of solvents and at the dodecane/water and dodecane/heavy-water interfaces using a combination of ultrafast spectroscopic techniques, including transient electronic absorption and time-resolved surface second-harmonic generation. Whereas the photophysics of a nonpolar DPP analogue is mostly independent of the solvent, the fluorescence decay of the push–pull DPP accelerates strongly by going from aprotic to protic solvents. As this effect increases with the polarity and the hydrogen-bond-donating ability of the solvent, it is attributed to the occurrence of H-bond-assisted nonradiative deactivation induced by the charge-transfer character of the excited state that favors the coupling of the molecule to the H-bond network of the solvent. At the dodecane/water interface, the excited-state lifetime is longer by a factor of ca. 20 than that estimated in pure water and increases further by a factor of about 3 when going to the dodecane/heavy-water interface. This isotope effect, that is more than twice as strong as that measured in bulk solutions, and molecular dynamic simulations indicate that the slowing down of the dynamics at the interface cannot be solely ascribed to a reduced accessibility of the DPP molecule to the aqueous phase. The slower excited-state decay is rather assigned to the conjunction of several effects, such as the strengthening of the H-bond network formed by the interfacial water molecules and the lower local polarity of the interfacial region

Fluorescence Probing of Thiol-Functionalized Gold Nanoparticles: Is Alkylthiol Coating of a Nanoparticle as Hydrophobic as Expected?

Understanding the interaction of fluorescent dyes with monolayer-protected gold nanoparticles (AuNPs) is of fundamental importance in designing new fluorescent nanomaterials. Among a variety of molecular sensors and reporters, fluorescent probes based on a 3-hydroxychromone (3HC) skeleton appear to be very promising. They exhibit the phenomenon of dual band emission, resulting from excited-state intramolecular proton transfer (ESIPT), known to be highly sensitive to a nature of microenvironment surrounding a fluorophore. In this study, dodecanethiol-protected gold nanoparticles were synthesized, and, owing to the transmission electron micrograph imaging, their average diameter was found to be ∼1.4 nm. Fluorescence titrations of the 3HC ESIPT probes with AuNPs in toluene solutions demonstrate significant changes in the intensity ratio of their normal and tautomeric emission bands, suggesting that the probe molecules become noncovalently bound to a dodecanethiol layer of AuNPs. Despite expected fluorescence quenching induced by close proximity to the metal surface, no fluorescence lifetime decrease was observed, indicating that a bound-fluorophore is shielded from a nanoparticle core. Further spectral analysis revealed that the ratiometric fluorescence changes could be interpreted as a consequence of intermolecular hydrogen bonding between a probe and residual ethanol molecules, trapped into the dodecanethiol shell of AuNPs during the synthesis. Evidences for residual traces of ethanol in the ligand shell of the nanoparticles were also observed in NMR spectra, suggesting that alkylthiol-coated gold nanoparticles may not be as hydrophobic as one could expect. To elucidate structural features of dodecanethiol-stabilized gold nanoparticles at the supramolecular level, a molecular dynamics (MD) model of AuNP was developed. The model was based on the all-atom CHARMM27 force field parameters and parametrized according to available experimental data of the synthesized AuNPs. Our MD simulations show that in bulk toluene the 3HC probe molecule becomes weakly bound to a dodecanethiol monolayer, so that a fluorophore favors residence in an outer shell of AuNP. In addition, MD simulations of transfer of AuNP from bulk ethanol to toluene demonstrate that a small population of ethanol molecules are able to penetrate deeply into the dodecanethiol layer and may indeed be trapped into the ligand shell of alkylthiol-functionalized gold nanoparticles. The results of our fluorescence experiments and molecular dynamics simulation suggest that 3-hydroxychromones can be used as a noncovalent fluorescent labeling agent for alkylthiol-stabilized noble metal nanoparticles

Fluorescence Probing of Thiol-Functionalized Gold Nanoparticles: Is Alkylthiol Coating of a Nanoparticle as Hydrophobic as Expected?

Understanding the interaction of fluorescent dyes with monolayer-protected gold nanoparticles (AuNPs) is of fundamental importance in designing new fluorescent nanomaterials. Among a variety of molecular sensors and reporters, fluorescent probes based on a 3-hydroxychromone (3HC) skeleton appear to be very promising. They exhibit the phenomenon of dual band emission, resulting from excited-state intramolecular proton transfer (ESIPT), known to be highly sensitive to a nature of microenvironment surrounding a fluorophore. In this study, dodecanethiol-protected gold nanoparticles were synthesized, and, owing to the transmission electron micrograph imaging, their average diameter was found to be ∼1.4 nm. Fluorescence titrations of the 3HC ESIPT probes with AuNPs in toluene solutions demonstrate significant changes in the intensity ratio of their normal and tautomeric emission bands, suggesting that the probe molecules become noncovalently bound to a dodecanethiol layer of AuNPs. Despite expected fluorescence quenching induced by close proximity to the metal surface, no fluorescence lifetime decrease was observed, indicating that a bound-fluorophore is shielded from a nanoparticle core. Further spectral analysis revealed that the ratiometric fluorescence changes could be interpreted as a consequence of intermolecular hydrogen bonding between a probe and residual ethanol molecules, trapped into the dodecanethiol shell of AuNPs during the synthesis. Evidences for residual traces of ethanol in the ligand shell of the nanoparticles were also observed in NMR spectra, suggesting that alkylthiol-coated gold nanoparticles may not be as hydrophobic as one could expect. To elucidate structural features of dodecanethiol-stabilized gold nanoparticles at the supramolecular level, a molecular dynamics (MD) model of AuNP was developed. The model was based on the all-atom CHARMM27 force field parameters and parametrized according to available experimental data of the synthesized AuNPs. Our MD simulations show that in bulk toluene the 3HC probe molecule becomes weakly bound to a dodecanethiol monolayer, so that a fluorophore favors residence in an outer shell of AuNP. In addition, MD simulations of transfer of AuNP from bulk ethanol to toluene demonstrate that a small population of ethanol molecules are able to penetrate deeply into the dodecanethiol layer and may indeed be trapped into the ligand shell of alkylthiol-functionalized gold nanoparticles. The results of our fluorescence experiments and molecular dynamics simulation suggest that 3-hydroxychromones can be used as a noncovalent fluorescent labeling agent for alkylthiol-stabilized noble metal nanoparticles