Surface Design for Immobilization of an Antimicrobial Peptide Mimic for Efficient Anti-Biofouling

Microbial surface attachment negatively impacts a wide range of devices from water purification membranes to biomedical implants. Mimics of antimicrobial peptides (AMPs) constituted from poly(N-substituted glycine) „peptoids“ are of great interest as they resist proteolysis and can inhibit a wide spectrum of microbes. We investigate how terminal modification of a peptoid AMP-mimic and its surface immobilization affect antimicrobial activity. We also demonstrate a convenient surface modification strategy for enabling alkyne–azide „click“ coupling on amino-functionalized surfaces. Our results verified that the N- and C-terminal peptoid structures are not required for antimicrobial activity. Moreover, our peptoid immobilization density and choice of PEG tether resulted in a „volumetric“ spatial separation between AMPs that, compared to past studies, enabled the highest AMP surface activity relative to bacterial attachment. Our analysis suggests the importance of spatial flexibility for membrane activity and that AMP separation may be a controlling parameter for optimizing surface anti-biofouling.     

Chromium complexes of an isomeric N-donor ligand, 2-[(N-arylamino)phenylazo]pyridine: amination reactions,X-ray structure,and redox properties

The chromium chemistry of two positional isomers of the ligand 2-[(N-arylamino)phenylazo]pyridine (HL(1)and HL(2)) are described. While the ligand HL(1) coordinates as a bischelating tridentate N,N,N-donor, [L(1)](-), with deprotonation of the amine nitrogen, its isomer HL(2) coordinates as a neutral bidentate N,N-donor. The amine nitrogen in this case remains protonated. Thus the reaction of CrCl(3).nH(2)O with HL(1) produced the brown cationic complex, [Cr(L(1))(2)](+), [1](+). The representative X-ray structure of [1a](ClO(4)) is reported. The two azo nitrogens of the anioinc tridentate ligand approach the metal center closest with Cr(1)-N(azo) av 1.862(6) A. There is a significant degree of ligand backbone conjugation in the coordinated ligands, which resulted in shortening of the C-N distances and also in lengthening of the diazo (N=N) distances. Two synthetic approaches for the synthesis of chromium complexes of HL(2) are investigated. The first approach is based on the substitution reaction, wherein all the coordinated CO ligands of Cr(CO)(6) were completely substituted by the three bidentate HL(2) ligands to produce a violet complex [Cr(HL(2))(3)]. The second approach is based on para-amination reaction of coordinated 2-(phenylazo)pyridine (pap). Thus the reaction of an inert complex, [CrCl(2)(pap)(2)], with ArNH(2) yields a mixed ligand complex, [CrCl(2)(pap)(HL(2))], 3. In this reaction one of the two coordinated pap ligands in [CrCl(2)(pap)(2)] undergoes amination at the para carbon (with respect to the diazo function) to yield HL(2) in situ. This metal-promoted transformation is authenticated by the X-ray structure determination of a representative complex, [CrCl(2)(pap)(HL(2a))], 3a. Notable differences in bond distances along the ligand backbones of the two coordinated ligands in 3a indicate different levels of metal-ligand overlap in this complex. All the chromium complexes of HL(2) are characterized by their intense blue-violet color. The frequencies of the visible range transitions in these complexes linearly correlate with the Hammett's substitution constant. Intraligand charge-transfer transitions in the visible region are believed to be responsible for the intense color. Redox properties of all these complexes are reported.     

Crossover from one to three dimensions for a gas of hard-core bosons

We develop a variational theory of the crossover from the one-dimensional (1D) regime to the 3D regime for ultracold Bose gases in thin waveguides. Within the 1D regime we map out the parameter space for fermionization, which may span the full 1D regime for suitable transverse confinement.     

Analysis of short-pulse laser photon transport through tissues for optical tomography

We describe a method for analyzing short-pulse laser propagation through tissues for the detection of tumors and inhomogeneities in tissues with the goal of developing a time-resolved optical tomography system. Traditional methods for analyzing photon transport in tissues usually involve the parabolic or diffusion approximation, which implies infinite speed of propagation of the optical signal. To overcome such limitations we calculate the transmitted and reflected intensity distributions, using the damped-wave hyperbolic P(1) and the discrete-ordinates methods, for a wide range of laser, tissue, and tumor parameters. The results are compared with the parabolic diffusion P(1) approximation.     

Cubyl-caged systems: regiochemical steering of cationic rearrangements by distal groups

Novel carbonium ion rearrangements of substituted 1,3-bishomocubanones $\text{3}$ & $\text{4}$ to tricyclo(4.2.0.0^3,8)octane and bicyclo(3.2.1)octane ring systems are reported.     

Topological descriptors in drug design and modeling studies

Molecular Diversity -     

Conditions for the onset of elastic and material instabilities in hyperelastic materials

Several constitutive inequalities have been proposed in the literature to quantify the notion that ‘stress increases with strain’ in an elastic material. Due to some inherent shortcomings in them, which we discuss, we propose a new tensorial criterion for isotropic materials. We also present necessary conditions in terms of elasticity tensors for the onset of elastic instabilities.     

A Rapid and Simple UPLC-MS–MS based Simultaneous Determination of the Medicinally Important E- and Z-Guggulsterone from Oleogum-Resins of Naturally Occurring Commiphora wightii Plants

A fast and simple method for simultaneous detection and quantification of the medicinally important E- and Z-guggulsterone from raw oleogum-resin of Commiphora wightii by UPLC was developed. Both E- and Z-guggulsterone were extracted from naturally occurring resin samples using ethyl acetate and methanol. Chromatographic separation of the analytes and their respective standards were performed on an Acquity UPLC BEH C₁₈ column followed by UV as well as a triple quadrupole detector in positive ionization mode. A linear gradient elution profile followed; mobile phase consisted of acetonitrile and 2 mM ammonium acetate in water. The method was validated over a range of 6.25 to 100 ng mL⁻¹ for both the guggulsterones. The calibration curves were linear with correlation coefficients of 0.9998 for E-guggulsterone and 0.9999 for Z-guggulsterone. The LOD and LOQ were 1.65 and 5.02 ng mL⁻¹ for E-guggulsterone and 2.57 and 7.79 ng mL⁻¹ for Z-guggulsterone respectively. The average recovery of E-guggulsterone (104.63%) and Z-guggulsterone (104.33%) achieved from spiked samples were consistent and reproducible. The intra- and inter-day assay precision of the analytes over the entire concentration range was less than 2%. The developed method required only 6 min to complete a run including 1 min to equilibrate the system and hence suitable for high throughput applications. Efficiency, reliability and accuracy of the developed method were evaluated by analyzing resin sample from different C. wightii populations. The result of this study offers improvement in terms of speed and sensitivity as compared to previously reported methods.

     

On further application of r as a metric for validation of QSAR models

Validation is a crucial aspect for quantitative structure–activity relationship (QSAR) model development. External validation is considered, in general, as the most conclusive proof of predictive capacity of a QSAR model. In the absence of truly external data set, external validation is usually performed on test set compounds, which are members of the original data set but not used in model development exercise. In the case of small data sets, QSAR researchers experience problem in model development due to the fact that the developed models may be less reliable on account of the small number of training set compounds and such models may also show poor external predictability because the models may not have captured all necessary features required for the particular structure–activity relationships. The present paper attempts to show that ‘true r_(LOO)’ statistic calculated based on the model derived from the undivided data set with application of variable selection strategy at each cycle of leave‐one‐out (LOO) validation may reflect external validation characteristics of the developed model thus obviating the requirement of splitting of the data set into training and test sets. This approach may be helpful in the case of small data sets as it uses all available data for model development and validation thus making the resulting model more reliable. Copyright © 2009 John Wiley & Sons, Ltd.     

Hydrogen bonding versus van der Waals interactions: competitive influence of noncovalent interactions on 2D self-assembly at the liquid-solid interface

The structures of the self-assembled monolayers of various 4-alkoxybenzoic acids physisorbed at the liquid-solid interface were established by employing scanning tunnelling microscopy (STM). This study has been essentially undertaken to explore the competitive influence of van der Waals and hydrogen-bonding interactions on the process of two-dimensional self-assembly. These acid derivatives form hydrogen-bonded dimers as expected; however, the dimers organise themselves in the form of relatively complex lamellae. The characteristic feature of these lamellae is the presence of regular discommensurations or kinks along the lamella propagation direction. The formation of kinked lamellae is discussed in light of the registry mechanism of the alkyl chains with the underlying graphite substrate. The location of the kinks along a lamella depends on the number (odd or even) of carbon atoms in the alkyl chain. This result indicates that concerted van der Waals interactions of the alkyl chain units introduce the odd/even chain-length effect on the surface-assembled supramolecular patterns. The odd/even effects are retained even upon complexation with a hydrogen-bond acceptor. However, as the solvent is changed from 1-phenyloctane to 1-octanoic acid, the kinked lamellae as well as the odd/even effects disappear. This solvent-induced convergence of supramolecular patterns is attained by means of co-crystallisation of octanoic acid molecules in the 2D crystal lattice, which is evident from high-resolution STM images. The solvent co-adsorption phenomenon is discussed in terms of competing van der Waals and hydrogen-bonding interactions.