Synthesis of macrocyclic diacyl/dialkyl glycerols containing disulfide tether and studies of their effects upon incorporation in DPPC membranes. Implications in the design of phospholipase A(2) modulators

A general method for the preparation of novel disulfide-tethered macrocyclic diacylglycerols (DAGs) has been described. Overall synthesis involved stepwise protection, acylation, and deprotection to yield the bis(omega-bromoacyl) glycerols. In the crucial macrocyclization step, a unique reagent, benzyltriethylammonium tetrathiomolybdate (BTAT), has been used to convert individual bis(omega-bromoacyl) glycerols to their respective macrocyclic disulfides. DAG 6, which had ether linkages between hydrocarbon chains and the glycerol backbone, was also synthesized from an appropriate precursor using a similar protocol. One of the DAGs (DAG 5) had a carbon-carbon tether instead of a disulfide one and was synthesized using modified Glaser coupling. Preparation of alpha-disulfide-tethered DAG (DAG 4) required an alternative method, as treatment of the bisbromo precursor with BTAT gave a mixture of several compounds from which separation of the target molecule was cumbersome. To avoid this problem, the bisbromide was converted to its corresponding dithiocyanate, which on further treatment with BTAT yielded the desired DAG (DAG 4) in good yield. Upon treatment with the reducing agent dithiothreitol (DTT), the DAGs that contain a disulfide tether could be quantitatively converted to their "open-chain" thiol analogues. These macrocyclic DAGs and their reduced "open-chain" analogues have been incorporated in DPPC vesicles to study their effect on model membranes. Upon incorporation of DAG 1 in DPPC vesicles, formation of new isotropic phases was observed by P-31 NMR, These isotropic phases disappeared completely on opening the macrocyclic ring by a reducing agent. The thermotropic properties of DPPC bilayers having DAGs (1-6) incorporated at various concentrations were studied by differential scanning calorimetry. Incorporation of DAGs in general reduced the cooperativity unit (CU) of the vesicles. Similar experiments with reduced "open-chain" DAGs incorporated in a DPPC bilayer indicated a recovery of CU with respect to their macrocyclic "disulfide" counterparts. The effect of inclusion of these DAGs on the activity of phospholipase A(2) (PLA(2)) was studied in vitro. Incorporation of DAC 1 in DPPC membranes potentiated both bee venom and cobra venom PLA(2) activities.

Strategies for three dimensional deployment of tethered satellites

Tethered satellites deployed from the Space Shuttle have been proposed for diverse applications. A funda- mental issue in the utilization of tethers is quick deployment and retrieval of the attached payload. Inordinate librations of the tether during deployment and retrieval is undesirable. The structural damping present in the system is too low to contain the librations. Rupp [1] proposed to control the tether reel located in the parent spacecraft to alter the tension in the tether, which in turn changes the stiffness and the damping of the system. Baker[2] applied the tension control law to a model which included out of plane motion. Modi et al.[3] proposed a control law that included nonlinear feedback of the out-of plane tether angular rate. More recently, nonlinear feedback control laws based on Liapunov functions have been proposed. Two control laws are derived in [4]. The first is based on partial decomposition of the equations of motion and utilization of a two dimensional control law developed in [5]. The other is based on a Liapunov function that takes into consideration out-of-plane motion. It is shown[4] that the control laws are effective when used in conjunction with out-of-plane thrusting. Fujii et al.,[6] used the mission function control approach to study the control law including aerodynamic drag effect explicitly into the control algorithm.

Matrix method for eigenstructure assignment - The multi-input case with application

The eigenvalue and eigenstructure assignment procedure has found application in a wide variety of control problems. In this paper a method for assigning eigenstructure to a linear time invariant multi-input system is proposed. The algorithm determines a matrix that has eigenvalues and eigenvectors at the desired locations. It is obtained from the knowledge of the open-loop system and the desired eigenstructure. Solution of the matrix equation, involving unknown controller gams, open-loop system matrices, and desired eigenvalues and eigenvectors, results hi the state feedback controller. The proposed algorithm requires the closed-loop eigenvalues to be different from those of the open-loop case. This apparent constraint can easily be overcome by a negligible shift in the values. Application of the procedure is illustrated through the offset control of a satellite supported, from an orbiting platform, by a flexible tether.

Matrix method for eigenstructure assignment - The multi-input case with application

The eigenvalue and eigenstructure assignment procedure has found application in a wide variety of control problems. In this paper a method for assigning eigenstructure to a Linear time invariant multi-input system is proposed. The algorithm determines a matrix that has eigenvalues and eigenvectors at the desired locations. It is obtained from the knowledge of the open-loop system and the desired eigenstructure. solution of the matrix equation, involving unknown controller gains, open-loop system matrices, and desired eigenvalues and eigenvectors, results in the state feedback controller. The proposed algorithm requires the closed-loop eigenvalues to be different from those of the open-loop case. This apparent constraint can easily be overcome by a negligible shift in the values. Application of the procedure is illustrated through the offset control of a satellite supported, from an orbiting platform, by a flexible tether,

Dynamics of intermittent force fluctuations in vesicular nanotubulation

Irregular force fluctuations are seen in most nanotubulation experiments. The dynamics behind their presence has, however, been neither commented upon nor modeled. A simple estimate of the mean energy dissipated in force drops turns out to be several times the thermal energy. This coupled with the rate dependent nature of the deformation reported in several experiments point to a dynamical origin of the serrations. We simplify the whole process of tether formation through a three-stage model of successive deformations of sphere to ellipsoid, neck-formation, and tubule birth and extension. Based on this, we envisage a rate-softening frictional force at the neck that must be overcome before a nanotube can be pulled out. Our minimal model includes elastic and visco-elastic deformation of the vesicle, and has built-in dependence on pull velocity, vesicle radius, and other material parameters, enabling us to capture various kinds of serrated force-extension curves for different parameter choices. Serrations are predicted in the nanotubulation region. Other features of force-extension plots reported in the literature such as a plateauing serrated region beyond a force drop, serrated flow region with a small positive slope, an increase in the elastic threshold with pull velocity, force-extension curves for vesicles with larger radius lying lower than those for smaller radius, are all also predicted by the model. A toy model is introduced to demonstrate that the role of the friction law is limited to inducing stick-slip oscillations in the force, and all other qualitative and quantitative features emerging from the model can only be attributed to other physical mechanisms included in the deformation dynamics of the vesicle. (C) 2014 AIP Publishing LLC.