Time-Resolved Surface-Enhanced Coherent Sensing of Nanoscale Molecular Complexes

Nanoscale real-time molecular sensing requires large signal enhancement, small background, short detection time and high spectral resolution. We demonstrate a new vibrational spectroscopic technique which satisfies all of these conditions. This time-resolved surface-enhanced coherent anti-Stokes Raman scattering (tr-SECARS) spectroscopy is used to detect hydrogen-bonded molecular complexes of pyridine with water in the near field of gold nanoparticles with large signal enhancement and a fraction of a second collection time. Optimal spectral width and time delays of ultrashort laser pulses suppress the surface-enhanced non-resonant background. Time-resolved signals increase the spectral resolution which is limited by the width of the probe pulse and allow measuring nanoscale vibrational dephasing dynamics. This technique combined with quantum chemistry simulations may be used for the investigation of complex mixtures at the nanoscale and surface environment of artificial nanostructures and biological systems

Pembinaan Instrumen Pengujian Daya Tahan Kardiovaskular (Ujian Blip) Menggunakan Teknologi Sensor Dan Paparan Digital

Daya tahan kardiovaskular merupakan aspek penting yang perlu diambil kira oleh seseorang atlit. Ujian blip merupakan salah satu ujian yang digunakan untuk mengetahui tahap daya tahan kardiovaskular. Tujuan utama kajian ini dijalankan adalah untuk merekacipta instrumen yang boleh memaparkan skor ujian blip. Sensor dan paparan digital adalah elemen-elemen elektronik yang utama dalam instrumen ini. Apabila sensor mengesan subjek melaluinya, instrumen akan menganalisis dapatan tersebut dan skor daya tahan kardiovaskular akan dipaparkan di paparan digital. Instrumen ini telah diuji ke atas 20 atlit dari kursus Sains Sukan dari Fakulti Pendidikan, UTM. Keupayaan instrumen ini juga diuji sehingga mencapai tahap maksimumnya di mana pembaris panjang digunakan sebagai pengganti atlit. Soal selidik diedarkan kepada atlit-atlit tersebut untuk mengetahui kualiti dan persepsi mereka terhadap instrumen yang dibina. Data yang diperolehi daripada soal selidik dianalisis menggunakan perisian Microsoft Excel 2003. Keputusan pengujian menunjukkan instrumen tersebut adalah efektif dalam membantu proses pengendalian ujian blip dengan tahap kesilapan yang minimum

Regio- and exo-π-facial selective 1,3-dipolar cycloaddition of α-(3-pyridyl)-N-phenylnitrone to norbornadiene: activation of a π-bond of norbornadiene and control of regiochemistry of nitrone cycloaddition by nitrone addition to the other double bond

Thermal cycloaddition of α-(3-pyridyl)-N-phenylnitrone to a π-bond in norbornadiene not only activates the other double bond towards 1,3-dipolar cycloaddition, it also regulates the regiochemistry of addition leading to regio- and exo-π-facial selective formation of novel 2:1 cycloadducts. A DFT analysis in terms of the global and local reactivity indices affords a rationalization of the obtained results

Synthesis of unsymmetrical substituted 1,4-dihydropyridines through thermal and microwave assisted [4+2] cycloadditions of 1-azadienes and allenic esters

Thermal and microwave assisted [4+2] cycloadditions of 1,4-diaryl-1-aza-1,3-butadienes with allenic esters lead to cycloadducts, which after a 1,3-H shift afford variedly substituted unsymmetrical 2-alkyl-1,4-diaryl-3-ethoxycarbonyl-1,4-dihydropyridines in high yields. Reactions carried out under microwave irradiation are cleaner and give higher yields with much shortened reaction times. Density functional theory (DFT) at the B3LYP/6-31G* level has been used to calculate geometric features of the reactants, barrier for s-trans to s-cis and reverse isomerization of azadienes (5a−d, 10a−e), dihedral angles between N1, C2, C3, and C4 atoms of azadienes along with various indices such as chemical hardness (η), chemical potential (μ), global electrophilicity (ω), and the difference in global electrophilicity (Δω) between the reacting pairs and Fukui functions (f+ and f--). The results revealed that s-trans is the predominant conformation of azadienes at ambient temperature and the barrier for conversion of the s-trans rotamer of 1-azadienes to s-cis may be the major factor influencing the chemoselectivity, i.e., [4+2] verses [2+2] cycloaddition. The regiochemistry of the observed cycloadditions is collated with the obtained local electrophilicity indices (Fukui functions). Transition states for the formation of both [4+2] and [2+2] cycloadducts as located at the PM3 level indicate that the transition state for the formation of [4+2] cycloadducts has lower energy, again supporting the earlier conclusion that preferred formation of [4+2] cycloaaducts at higher temperature may be a consequence of barrier for s-trans to s-cis transformation of 1-azadienes

Molecular Dynamics Simulation of the Oil Sequestration Properties of a Nonionic Rhamnolipid

A detailed molecular dynamics simulation study is presented on the behavior of aggregates composed of the nonionic monorhamnolipid α-rhamnopyranosyl-β-hydroxydecanoyl-β-hydroxydecanoate (Rha-C10-C10) and decane in bulk water. A graph theoretical approach was utilized to characterize the size and composition of the many aggregates generated in our simulations. Overall, we observe that the formation of oil in Rha-C10-C10 aggregates is a favorable process. Detailed analysis on the surfactant/oil aggregate shows that larger aggregates are stable. The shape and size of the aggregates are widely distributed, with the majority of the aggregates preferring ellipsoidal or cylindrical structures. Irrespective of the decane concentration in the system, we did not observe free decane in any of the simulations. Further insights into the binding energy of decane were carried out using free-energy perturbation calculations. The results showed that the trapped decane molecules provide stability to the Rha-C10-C10 aggregates of size <i>N</i> = 50 which are shown to be unstable in our previous study and allow for the growth of larger aggregates than pure Rha-C10-C10 in water. The density profile plots show that decane molecules encapsulated inside the aggregate preferred to remain closer to the center of mass. This study points to the feasibility of using this biosurfactant as an environmental remediation agent

Structural Properties of Nonionic Monorhamnolipid Aggregates in Water Studied by Classical Molecular Dynamics Simulations

Molecular dynamics simulations were carried out to investigate the structure and stabilizing factors of aggregates of the nonionic form of the most common congener of monorhamnolipids, α-rhamnopyranosyl-β-hydroxydecanoyl-β-hydroxydecanoate (Rha-C10-C10), in water. Aggregates of size ranging from 5 to 810 monomers were observed in the simulation forming spherical and ellipsoidal structures, a torus-like structure, and a unilamellar vesicle. The effects of the hydrophobic chain conformation and alignment in the aggregate, role of monomer···monomer and monomer···water H-bonds, and conformations of monomers in the aggregate were studied in detail. The unilamellar vesicle is highly stable due to the presence of isolated water molecules inside the core adding to the binding energy. Dissociation of a monomer from a larger micellar aggregate is relatively easy compared to that from smaller aggregates as seen from potential of mean force calculations. This analysis also shows that monomers are held more strongly in aggregates of Rha-C10-C10 than the widely used surfactant sodium dodecyl sulfate. Comparisons between the aggregation behavior of nonionic and anionic forms of Rha-C10-C10 are presented

Molecular Dynamics Simulation of the Oil Sequestration Properties of a Nonionic Rhamnolipid

A detailed molecular dynamics simulation study is presented on the behavior of aggregates composed of the nonionic monorhamnolipid α-rhamnopyranosyl-β-hydroxydecanoyl-β-hydroxydecanoate (Rha-C10-C10) and decane in bulk water. A graph theoretical approach was utilized to characterize the size and composition of the many aggregates generated in our simulations. Overall, we observe that the formation of oil in Rha-C10-C10 aggregates is a favorable process. Detailed analysis on the surfactant/oil aggregate shows that larger aggregates are stable. The shape and size of the aggregates are widely distributed, with the majority of the aggregates preferring ellipsoidal or cylindrical structures. Irrespective of the decane concentration in the system, we did not observe free decane in any of the simulations. Further insights into the binding energy of decane were carried out using free-energy perturbation calculations. The results showed that the trapped decane molecules provide stability to the Rha-C10-C10 aggregates of size <i>N</i> = 50 which are shown to be unstable in our previous study and allow for the growth of larger aggregates than pure Rha-C10-C10 in water. The density profile plots show that decane molecules encapsulated inside the aggregate preferred to remain closer to the center of mass. This study points to the feasibility of using this biosurfactant as an environmental remediation agent

Domino routes to substituted benzoindolizines: tandem reorganization of 1,3-dipolar cycloadducts of nitrones with allenic esters/ketones and alternative cycloaddition–palladium catalyzed cyclization pathway

Reactions of C-(4-oxo-4H[1]benzopyran-3-yl)-N-phenyl nitrones (7) with allenic esters (8a–c) and allenic ketones (18a–d) furnish benzoindolizines (9a–k, 19a–d) in good yields. The formation of benzoindolizines is postulated to involve regioselective addition of 1,3-dipole to C2–C3 π bond of allenic esters/ketones followed by domino transformation of the cycloadducts, which involve an intramolecular aza Diels–Alder reaction in the intermediate C. DFT calculations of various parameters for diene and dienophile components in the proposed intermediate C have revealed that conformational constraints imposed by the alkyl groups (R=Me, Et) favor intramolecular aza-Diels–Alder cycloaddition. An alternative domino route to benzoindolizines (9a,d,g) involving sequential one-pot cycloaddition of azadienes (22a–c) with silyl-enol ether (23) followed by palladium(0)-catalyzed Heck coupling reaction has also been developed. Both these approaches represent novel domino routes for the synthesis of benzoindolizines

Evolution of Aggregate Structure in Solutions of Anionic Monorhamnolipids: Experimental and Computational Results

The evolution of solution aggregates of the anionic form of the native monorhamnolipid (mRL) mixture produced by <i>Pseudomonas aeruginosa</i> ATCC 9027 is explored at pH 8.0 using both experimental and computational approaches. Experiments utilizing surface tension measurements, dynamic light scattering, and both steady-state and time-resolved fluorescence spectroscopy reveal solution aggregation properties. All-atom molecular dynamics simulations on self-assemblies of the most abundant monorhamnolipid molecule, l-rhamnosyl-β-hydroxy­decanoyl-β-hydroxy­decanoate (Rha-C10-C10), in its anionic state explore the formation of aggregates and the role of hydrogen bonding, substantiating the experimental results. At pH 8.0, at concentrations above the critical aggregation concentration of 201 μM but below ∼7.5 mM, small premicelles exist in solution; above ∼7.5 mM, micelles with hydrodynamic radii of ∼2.5 nm dominate, although two discrete populations of larger lamellar aggregates (hydrodynamic radii of ∼10 and 90 nm) are also present in solution in much smaller number densities. The critical aggregation number for the micelles is determined to be ∼26 monomers/micelle using fluorescence quenching measurements, with micelles gradually increasing in size with monorhamnolipid concentration. Molecular dynamics simulations on systems with between 10 and 100 molecules of Rha-C10-C10 indicate the presence of stable premicelles of seven monomers with the most prevalent micelle being ∼25 monomers and relatively spherical. A range of slightly larger micelles of comparable stability can also exist that become increasing elliptical with increasing monomer number. Intermolecular hydrogen bonding is shown to play a significant role in stabilization of these aggregates. In total, the computational results are in excellent agreement with the experimental results

Modulation of Aldose Reductase Inhibition by Halogen Bond Tuning

In this paper, we studied a designed series of aldose reductase (AR) inhibitors. The series was derived from a known AR binder, which had previously been shown to form a halogen bond between its bromine atom and the oxygen atom of the Thr-113 side chain of AR. In the series, the strength of the halogen bond was modulated by two factors, namely bromine–iodine substitution and the fluorination of the aromatic ring in several positions. The role of the single halogen bond in AR–ligand binding was elucidated by advanced binding free energy calculations involving the semiempirical quantum chemical Hamiltonian. The results were complemented with ultrahigh-resolution X-ray crystallography and IC₅₀ measurements. All of the AR inhibitors studied were shown by X-ray crystallography to bind in an identical manner. Further, it was demonstrated that it was possible to decrease the IC₅₀ value by about 1 order of magnitude by tuning the strength of the halogen bond by a monoatomic substitution. The calculations revealed that the protein–ligand interaction energy increased upon the substitution of iodine for bromine or upon the addition of electron-withdrawing fluorine atoms to the ring. However, the effect on the binding affinity was found to be more complex due to the change of the solvation/desolvation properties within the ligand series. The study shows that it is possible to modulate the strength of a halogen bond in a protein–ligand complex as was designed based on the previous studies of low-molecular-weight complexes