A Nexus between Theory and Experiment: Non‐Empirical Quantum Mechanical Computational Methodology Applied to Cucurbit[n]uril⋅Guest Binding Interactions

A training set of eleven X‐ray structures determined for biomimetic complexes between cucurbit[n]uril (CB[7 or 8]) hosts and adamantane‐/diamantane ammonium/aminium guests were studied with DFT‐D3 quantum mechanical computational methods to afford ΔG_calcd binding energies. A novel feature of this work is that the fidelity of the BLYP‐D3/def2‐TZVPP choice of DFT functional was proven by comparison with more accurate methods. For the first time, the CB[n] ? guest complex binding energy subcomponents [for example, ΔE_dispersion, ΔE_{electrostatic}, ΔG_solvation, binding entropy (?TΔS), and induced fit E_{deformation(host)}, E_{deformation(guest)}] were calculated. Only a few weeks of computation time per complex were required by using this protocol. The deformation (stiffness) and solvation properties (with emphasis on cavity desolvation) of cucurbit[n]uril (n=5, 6, 7, 8) isolated host molecules were also explored by means of the DFT‐D3 method. A high ρ²=0.84 correlation coefficient between ΔG_exptl and ΔG_calcd was achieved without any scaling of the calculated terms (at 298 K). This linear dependence was utilized for ΔG_calcd predictions of new complexes. The nature of binding, including the role of high energy water molecules, was also studied. The utility of introduction of tethered [‐(CH₂)_nNH₃]⁺ amino loops attached to N,N‐dimethyl‐adamantane‐1‐amine and N,N,N′,N′‐tetramethyl diamantane‐4,9‐diamine skeletons (both from an experimental and a theoretical perspective) is presented here as a promising tool for the achievement of new ultra‐high binding guests to CB[7] hosts. Predictions of not yet measured equilibrium constants are presented herein.     

Towards a total synthesis of the new anticancer agent mensacarcin: synthesis of the carbocyclic core

A synthesis of the carbocyclic core associated with the new anticancer agent mensacarcin (1) is reported. The strategy involves the synthesis of several novel highly substituted aromatic compounds, such as 12 and 23. The lithium derivative of 12 readily engages in a nucleophilic addition to benzaldehyde 4 to provide the diphenylcarbinol rac-15. The analogous benzyl ether rac-16 undergoes an intramolecular Heck reaction to provide the required tetrahydroanthracene rac-17, which can be transformed into the key tricyclic methyl ether rac-20. In a second approach, the lithium derivative of 21 is added to the hexasubstituted benzaldehyde 23 to give the diphenylcarbinol rac-35. Subsequent methylation to rac-36 followed by an intramolecular Heck reaction provides tricycle rac-37. Similarly, the oxidised compound 40 provides an electronically more suitable intramolecular Heck partner to afford compound 41. Further transformations of these substrates leads to rac-43, which incorporates the core structure of mensacarcin (1).     

Coordination in decentralized assembly systems with uncertain component yields

The literature on assembly systems with random component yields has focused on centralized systems, where a single decision maker chooses all components’ production quantities and incurs all the costs. We consider a decentralized setting where the component suppliers choose their production quantities based solely on their own cost/reward structure, and the assembly firm makes ordering decisions based on its own cost/reward structure. When the suppliers control their inputs but the outputs exhibit random yields, coordination in such systems becomes quite complex. In such situations, incentive alignment control mechanisms are needed so that the suppliers will choose production quantities as in the centralized system case. One such mechanism is to penalize the supplier with the worse delivery performance. We analyze the conditions under which system coordination is achieved while respecting participation constraints. Further, we determine the optimal component ordering policy for the assembly firm and derive the optimal coordinating penalties.     

Two-dimensional differential adherence of neuroblasts in laser micromachined CAD/CAM agarose channels

Laser micromachining of hydrophobic gels into CAD/CAM patterns was used to develop differentially adherent surfaces and induce the attachment of B35 rat neuroblasts that would later form engineered nerve bundles. Narrow channels, 60-400 μm wide, were micromachined in a 2% agarose gel using an ArF laser, and subsequently filled with an extracellular matrix gel. Upon the addition of 1 ml of a 2 × 104 cells/ml neuroblast suspension, the cells selectively adhered to the ECM-lined channels in a non-confluent manner and we monitored their growth at various time points. The adherent neuroblasts were fluorescently imaged with a propidium iodide live/dead assay, which revealed that the cells were alive within the channels. After 72 h growth, the neuroblasts grew, proliferated, and differentiated into nerve bundles. The fully grown 1 cm long nerve bundle organoids maintained an aspect ratio on the order of 100. The results presented in this paper provide the foundation for laser micromachining technique to develop bioactive substrates for development of three-dimensional tissues. Laser micromachining offers rapid prototyping of substrates, excellent resolution, control of pattern depth and dimensions, and ease of fabrication.     

Generation of sub wavelength multiple focal hole segments using azimuthally polarized annular multi-Gaussian beam

We propose a new approach for generating multiple focal hole segment of sub wavelength size, by tight focusing of phase modulated annular multi-Gaussian beam. The focusing properties are investigated theoretically by vector diffraction theory. We observed that focal segment with multiple focal rings structure separated with different axial distance can be generated by properly tuning the phase of the incident azimuthally polarized annular multi-Gaussian beam. Potential applications of this focal shaping technique are also discussed.     

Determination of gatifloxacin and ornidazole in tablet dosage forms by high-performance thin-layer chromatography.

A simple and sensitive high-performance thin-layer chromatography (HPTLC) method has been developed for the quantitative estimation of gatifloxacin and ornidazole in its combined dosage forms. Gatifloxacin and ornidazole were chromatographed on silica Gel 60 F(254) TLC plate using n-butanol:methanol:ammonia (6 M) (8:1:1.5 v/v) as the mobile phase and scanned at 302 nm using a Camag TLC Scanner 3. The R(f) value of gatifloxacin and ornidazole was found to be 0.21 +/- 0.02 and 0.76 +/- 0.04, respectively. The linearity of gatifloxacin and ornidazole were in the range of 100 - 500 ng/spot and 250 - 1250 ng/spot, respectively. The limit of detection was found to be 40 ng/spot for gatifloxacin and 100 ng/spot for ornidazole. The proposed method was applied for the determination of gatifloxacin and ornidazole in combined dosage forms.     

Lipopeptides from the Banyan Endophyte, Bacillus subtilis K1: Mass Spectrometric Characterization of a Library of Fengycins

Mass spectrometric analysis of a banyan endophyte, Bacillus subtilis K1, extract showing broad spectrum antifungal activity revealed a complex mixture of lipopeptides, iturins, surfactins, and fengycins. Fractionation by reversed-phase high performance liquid chromatography (HPLC) facilitated a detailed analysis of fengycin microheterogeneity. Matrix assisted laser desorption ionization (MALDI) and electrospray ionization (ESI) mass spectrometric studies permitted the identification of several new fengycin variants. Four major sites of heterogeneity are identified: (1) N-terminus ??-hydroxy fatty acid moiety, where chain length variation and the presence of unsaturation occur, (2) position 6 (Ala/Val/Ile/Leu), (3) position 10 (Val/Ile) within the macrocyclic ring, and (4) Gln to Glu replacement at position 8, resulting in fengycin variants that differ in mass by 1?Da. Diagnostic fragment ions provide a quick method for localizing the sites of variation in the macrocycle or the linear segment. Subsequent establishment of the sequences is achieved by MS/MS analysis of linear fengycin species produced by hydrolysis of the macrocyclic lactone. Unsaturation in the fatty acid chain and the presence of linear precursors in the B. subtilis K1 extract are also established by mass spectrometry. The anomalous distribution of intensities within isotopic multiplets is a diagnostic for Gln/Glu replacements. High resolution mass spectrometry facilitates the identification of fengycin species differing by 1?Da by localizing the variable position (Gln₈/Glu₈) in the fengycin variants.     

Mn(III) mixed‐ligand complexes with bis‐pyrazolones and ciprofloxacin drug: synthesis,characterization and antibacterial activities

The fluoroquinolone family member ciprofloxacin is well known for its drug design and coordinating ability towards metal ions. The coordination chemistry of this drug with metal ions of biological and pharmaceutical importance is of considerable interest. Novel Mn(III) mixed‐ligand complexes of ciprofloxacin with various bis‐pyrazolone‐based dinegative bidentate ligands were synthesized and characterized on the basis of their physical properties, magnetic susceptibility measurements, (FT‐IR and electronic) spectral studies. The FAB‐mass spectrum of [Mn(A⁹)(L)(H₂O)₂]·H₂O [where H₂A⁹ = 4,4′‐(p‐tolylmethylene)bis(3‐methyl‐1‐phenyl‐4,5‐dihydro‐1H‐pyrazol‐5‐ol) and HL = 1‐cyclopropyl‐6‐fluoro‐4‐oxo‐7‐(piperazin‐1‐yl)‐1,4‐dihydroquinoline‐3‐carboxylic acid] was determined. All the synthesized compounds were screened for their bioactivity. The mixed‐ligand complexes exhibited comparable activities against two Gram‐negative (Escherichia coli and Serratia marcescens) and two Gram‐positive (Staphylococcus aureus and Bacillus subtilis) microorganisms. Copyright © 2011 John Wiley & Sons, Ltd.     

X-ray Debye temperature of mechanically milled Ni0.5Zn0.5Fe2O4 spinel ferrite

The X-ray Debye temperatures, θ _M , of spinel ferrite composition Ni_0.5Zn_0.5Fe₂O₄, mechanically milled upto 9 hrs, were determined from integrated intensities of selected Bragg reflections. The θ _M was found to increase with milling time. The results are explained in the light of milling induced grain orientation and surface effect. The values of θ _M were found to be lower as compared to the Debye temperatures obtained from infrared spectral data analysis. The difference can be explained on the basis of increase in an excess free volume in the form of vacancies and vacancy clusters associated with grain boundaries.     

On the nonlinear slewing dynamics and control of the Space Station based Mobile Servicing System

A relatively general Lagrangian formulation for studying the nonlinear dynamics and control of space-craft with interconnected flexible members in a tree-type topology is developed. Versatility of the formulation is illustrated through a dynamical study of the Space Station based two-link Mobile Servicing System (MSS). The performance of the MSS undergoing inplane and out-of-plane slewing maneuvers is compared. Results indicate that, in absence of control, the maneuvers induce undesirable librational motion of the Space Station as well as vibration of the links. Nonlinear control, based on the Feedback Linearization Technique (FLT), appears promising. Quasi-Closed Loop Control (QCLC), a variation of the FLT, is applied to control the libration of the Space Station. Once the attitude of the Space Station is controlled, the performance of the MSS improves significantly. For a 5-minute maneuver of the MSS, the maximum control torque required is only 34.5 Nm.Nomenclature f _i ¹ , f _i,j ¹ fundamental frequency of bodies B _i and B _i,j, respectively - l _c, l _i, l _i,j length of bodies B _c, B _i, and B _i,j, respectively - m _c, m _i, m _i,j mass of bodies B _c, B _i, and B _i,j, respectively - % MathType!MTEF!2!1!+-% feaafiart1ev1aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn% hiov2DGi1BTfMBaeXafv3ySLgzGmvETj2BSbqefm0B1jxALjhiov2D% aebbfv3ySLgzGueE0jxyaibaiGc9yrFr0xXdbba91rFfpec8Eeeu0x% Xdbba9frFj0-OqFfea0dXdd9vqaq-JfrVkFHe9pgea0dXdar-Jb9hs% 0dXdbPYxe9vr0-vr0-vqpWqaaeaabiGaciaacaqabeaadaqaaqGaaO% qaaerbhv2BYDwAHbacfiGab8xCayaaraqefavySfgDP52BGWuAU9gD% 5bxzaGGbciaa+zgacaWFSaGaa8hiaiqa-fhagaqeaiaa-jhaaaa!4B1F!\[\bar qf, \bar qr\] vector representing flexible and rigid generalized coordinates - % MathType!MTEF!2!1!+-% feaafiart1ev1aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn% hiov2DGi1BTfMBaeXafv3ySLgzGmvETj2BSbqefm0B1jxALjhiov2D% aebbfv3ySLgzGueE0jxyaibaiGc9yrFr0xXdbba91rFfpec8Eeeu0x% Xdbba9frFj0-OqFfea0dXdd9vqaq-JfrVkFHe9pgea0dXdar-Jb9hs% 0dXdbPYxe9vr0-vr0-vqpWqaaeaabiGaciaacaqabeaadaqaaqGaaO% qaaerbhv2BYDwAHbacfiGaa8hkaiqa-fhagaqeaiaa-jhacaWFPaqe% favySfgDP52BGWuAU9gD5bxzaGGbciaa+rgaaaa!4A18!\[(\bar qr)d\] vector representing the desired rigid generalized coordinates - (I _xx)k, (I _yy)k, (I _zz)k principal inertia of body B _k about X _k, Y _k, and Z _k axes, respectively; ksc, i or i, j - K _p, K _v displacement and velocity gain matrices - N _q total number of generalized coordinates - % MathType!MTEF!2!1!+-% feaafiart1ev1aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn% hiov2DGi1BTfMBaeXafv3ySLgzGmvETj2BSbqefm0B1jxALjhiov2D% aebbfv3ySLgzGueE0jxyaibaiGc9yrFr0xXdbba91rFfpec8Eeeu0x% Xdbba9frFj0-OqFfea0dXdd9vqaq-JfrVkFHe9pgea0dXdar-Jb9hs% 0dXdbPYxe9vr0-vr0-vqpWqaaeaabiGaciaacaqabeaadaqaaqGaaO% qaaerbwvMCKfMBHbacfiGab8xuayaaraqefavySfgDP52BGWuAU9gD% 5bxzaGGbciaa+zgaieaacaqFSaGaa0hiaiqa-ffagaqeaGqaciaa8j% haaaa!4AEF!\[\bar Qf, \bar Qr\] control effort vectors for flexible and rigid coordinates, respectively - Q , Q , Q control effort for pitch, roll and yaw degree of freedom, respectively - _k ^y , _k ^z tip deflection of a beam type appendage (B _k) in the Y _k and Z _k directions, respectively.