Pedro A. Derosa

Simulation of transport and extravasation of nanoparticles in tumors which exhibit enhanced permeability and retention effect

Determining the factors that influence the delivery of sub-micron particles to tumors and understanding the relative importance of each of these factors is fundamental to the optimization of the particle delivery process. In this paper, a model that combines random walk with the pressure driven movement of nanoparticles in a tumor vasculature is presented. Nanoparticle movement in a cylindrical tube with dimensions similar to the tumors blood capillary with a single pore is simulated. Nanoparticle velocities are calculated as a pressure driven flow over imposed to Brownian motion. The number and percentage of nanoparticles leaving the blood vessel through a single pore is obtained as a function of pore size, nanoparticle size and concentration, interstitial pressure, and blood pressure. The model presented here is able to determine the importance of these controllable parameters and thus it can be used to understand the process and predict the best conditions for nanoparticle-based treatment. The results indicate that the nanoparticle delivery gradually increases with pore size and decreases with nanoparticle size for tumors with high interstitial fluid pressure (in this work we found this behavior for head and neck carcinoma and for metastatic melanoma with interstitial pressures of 18mmHg and 19mmHg, respectively). For tumors with lower interstitial fluid pressure (rectal carcinoma with 15.3mmHg) however, delivery is observed to have little sensitivity to particle size for almost the entire nanoparticle size range. Though an increase in nanoparticle concentration increases the number of nanoparticles being delivered, the efficiency of the delivery (percentage of nanoparticles delivered) is found to remain closely unaffected.

A combined semiempirical-DFT study of oligomers within the finite-chain approximation, evolution from oligomers to polymers.

A computationally cheap approach combining time‐independent density functional theory (TIDFT) and semiempirical methods with an appropriate extrapolation procedure is proposed to accurately estimate geometrical and electronic properties of conjugated polymers using just a small set of oligomers. The highest occupied molecular orbital–lowest unoccupied molecular orbital gap (HLG) obtained at a TIDFT level (B3PW91) for two polymers, trans‐polyacetylene ‐the simplest conjugated polymer, and a much larger poly(2‐methoxy‐5‐(2,9‐ethyl‐hexyloxy)‐1,4‐phenylenevinylene (MEH‐PPV) polymer converge to virtually the same asymptotic value than the excitation energy obtained with time‐dependent DFT (TDDFT) calculations using the same functional. For TIDFT geometries, the HLG is found to converge to a value within the experimentally accepted range for the band gap of these polymers, when an exponential extrapolation is used; however if semiempirical geometries are used, a linear fit of the HLG versus 1/n is found to produce the best results. Geometrical parameters are observed to reach a saturation value in good agreement with experimental information, within the length of oligomers calculated here and no extrapolation was considered necessary. Finally, the performance of three different semiempirical methods (AM1, PM3, and MNDO) and for the TIDFT calculations, the performance of 7 different full electron basis sets (6‐311+G**, 6‐31+ +G**, 6‐311+ +G**, 6‐31+G**, 6‐31G**, 6‐31+G*, and 6‐31G) is compared and it is determined that the choice of semiempirical method or the basis set does not significantly affect the results.

Distance-Dependent Measurements of the Conductance of Porphyrin Nanorods Studied with Conductive Probe Atomic Force Microscopy

Protocols for nanopatterning porphyrins on Au(111) were developed based on immersion particle lithography. Porphyrins with and without a central metal ion, 5,10,15,20-tetraphenyl-21H,23H-porphyrin (TPP) and 5,10,15,20-tetraphenyl-21H,23H-porphyrin cobalt(II) (CoTPP), were selected for study, which spontaneously formed nanorod geometries depending on concentration parameters. The elongated shapes of the nanorods offers an opportunity for successive distance-dependent conductive probe atomic force microscopy (CP-AFM) measurements along the length of the nanorods. To prepare patterns of TPP and CoTPP nanorods, a mask of silica mesospheres was placed on gold substrates to generate nanoholes within an alkanethiol matrix film. The nanoholes prepared by particle lithography with an immersion step were backfilled with porphyrins by a second immersion step. By controlling the concentration and immersion interval, nanorods of porphyrins were generated with one end of the nanostructure attached to gold within a nanohole. The porphyrin nanorods exhibited slight differences in dimensions at the nanoscale to enable size-dependent measurements of conductive properties. The conductivity along the horizontal direction of the nanorods was evaluated with CP-AFM studies. Changes in conductivity were measured along the long axis of TPP and CoTPP nanorods. The TPP nanorods exhibited conductive profiles of an insulating material, and the CoTPP nanorods exhibited profiles of a semiconductor. The experiments demonstrate the applicability of particle lithography for preparing unique and functional surface platforms of porphyrins to measure distance-dependent conductive properties on gold.

CTViz: A tool for the visualization of transport in nanocomposites

A visualization tool (CTViz) for charge transport processes in 3-D hybrid materials (nanocomposites) was developed, inspired by the need for a graphical application to assist in code debugging and data presentation of an existing in-house code. As the simulation code grew, troubleshooting problems grew increasingly difficult without an effective way to visualize 3-D samples and charge transport in those samples. CTViz is able to produce publication and presentation quality visuals of the simulation box, as well as static and animated visuals of the paths of individual carriers through the sample. CTViz was designed to provide a high degree of flexibility in the visualization of the data. A feature that characterizes this tool is the use of shade and transparency levels to highlight important details in the morphology or in the transport paths by hiding or dimming elements of little relevance to the current view. This is fundamental for the visualization of 3-D systems with complex structures. The code presented here provides these required capabilities, but has gone beyond the original design and could be used as is or easily adapted for the visualization of other particulate transport where transport occurs on discrete paths.

Conductive-probe measurements with nanodots of free-base and metallated porphyrins.

The conductive properties of nanodots of model porphyrins were investigated using conductive-probe atomic force microscopy (CP-AFM). Porphyrins provide excellent models for preparing surface structures that can potentially be used as building blocks for devices. The conjugated, planar structure of porphyrins offers opportunities for tailoring the electronic properties. Two model porphyrins were selected for studies, 5,10,15,20-tetraphenyl-21H,23H-porphine cobalt(II) (TPC) and its metal-free analog 5,10,15,20-tetraphenyl-21H,23H-porphine (TPP). Nanodots of TPP and TPC were prepared within a dodecanethiol resist on gold using particle lithography. The nanopatterned surfaces exhibit millions of reproducible test structures of porphyrin nanodots. The porphyrin nanodots have slight differences in dimensions at the nanoscale, to enable size-dependent measurements of conductive properties. The size of the nanodots corresponds to ∼5-7 layers of porphyrin. The conductivity along the vertical direction of the nanodots was measured by applying a bias voltage between the gold surface and a metal-coated AFM cantilever. The TPP nanodots exhibited semi-conductive profiles while the TPC nanodots exhibited profiles that are typical of a conductive film or molecular wire. The engineered nanostructures of porphyrins provide an effective platform for investigation and measurement of conductive properties.

Selective complexation of alkali metal ions using crown ethers derived from calix[4]arenes: a computational investigation of the structural and energetic factors

A systematic analysis of the structural, energetic, and thermodynamic factors involved in alkali metal (i.e., Na+, K+, Rb+, and Cs+) complexation by four calix[4]arene crown-6 ethers in the 1,3-alternate conformation is presented here. The ligands (or hosts) in this work are identical to, or closely related to, the four molecules whose selectivity towards complexing Na+, K+, Rb+, and Cs+ from aqueous solutions was studied experimentally by Casnati et al. (Tetrahedron 60(36):7869–7876, 2004). By dividing the complexation process into three different contributions, namely, the binding energy of the ion to the crown, the elastic energy of the crown, and the solvation effect, it becomes clear that the primary factor that determines ion selectivity in crown-6-ethers is not the size of the crown, as currently believed. All four crown ethers preferentially complex with the smallest ion (Na+) in the gas phase. In the condensed phase, these crown-6 ethers preferentially complex with the larger ions only because the aqueous solvation energies of the alkali metal ions make it thermodynamically less favorable to extract the smaller ions from aqueous solutions. This suggests that the current understanding of the factors influencing the selectivity of metal ion complexation by crown ethers may be in need of revision.

The role of agglomeration in the conductivity of carbon nanotube composites near percolation

A detailed study of agglomeration in composite materials containing carbon nanotubes (CNT) is presented. Three dimensional samples with different degrees of agglomeration were created in three different ways, leading to a wider range of geometries available to study. Virtual charges are injected into the computer-generated samples and move through these samples according to a Monte Carlo hopping algorithm. Results show that there is an optimal level of agglomeration that is actually beneficial for charge transport at low volume concentrations, lowering the percolation threshold. It is found that near percolation, a more uniform CNT distribution (less agglomeration) leads to more conductive paths, but with a lower mobility. The optimum level of agglomeration comes from a trade off between these two properties. Beyond this optimum agglomeration state, it is observed that conductivity tends to decrease as dispersion increases at all concentrations studied here. At high concentration (percolated samples), where CNT clumps merge, conductivity seems to be less sensitive to agglomeration.A detailed study of agglomeration in composite materials containing carbon nanotubes (CNT) is presented. Three dimensional samples with different degrees of agglomeration were created in three different ways, leading to a wider range of geometries available to study. Virtual charges are injected into the computer-generated samples and move through these samples according to a Monte Carlo hopping algorithm. Results show that there is an optimal level of agglomeration that is actually beneficial for charge transport at low volume concentrations, lowering the percolation threshold. It is found that near percolation, a more uniform CNT distribution (less agglomeration) leads to more conductive paths, but with a lower mobility. The optimum level of agglomeration comes from a trade off between these two properties. Beyond this optimum agglomeration state, it is observed that conductivity tends to decrease as dispersion increases at all concentrations studied here. At high concentration (percolated samples), whe...

Spin-Controlled Conductivity in a Thiophene-Functionalized Iron-Bis(dicarbollide)

The relationship between spin state and conductivity is studied for a thiophene-functionalized iron(III)-bis(dicarbollide) with one or two thiophenes at each end of the cage. Iron has a high ground state spin that can be adjusted by external electromagnetic fields to produce different magnetic states. The hypothesis explored here is that changes in the spin state of these Fe-containing molecules can lead to significant changes in molecular conductivity. Two examples of the possible application of such spin-dependent conductivity are its use as a molecular switch, the basic building block in digital logic, or as a memory bit. The molecules were first optimized using the Becke-3 Lee–Yang–Parr functional (B3LYP) with the 6-31G(d) basis set. A relaxed molecular geometry at each spin state was then placed between gold electrodes to conduct spin-polarized electron transport calculations with the density functional theory/non-equilibrium Green’s functions formalism. The revised Perdew–Burke–Ernzerhf solids exchange–correlation functional (PBES) with double zeta polarized basis set was used. The result of these calculations show that the conductivity increases with the spin state. The cage structure is shown to exhibit fully delocalized molecular orbitals (MOs) appropriate for high conductivity and thus, in this system, the conductivity depends on the position of the MOs relative to the Fermi level. Minority spins are responsible for the conductivity of the doublet spin state while majority spins dominate for the quartet and sextet spin states as they are found closer to the Fermi level when they are occupied. Energy calculations predict a difference in energy between the more and the less conductive spin states (sextet and doublet respectively) that is 15–20 times greater than the thermal energy, which would imply stability at room temperature; however, the energy difference is sufficiently small that transitions between spin states can be induced.

Design and optimization of a radiation detector for ground and spaced-based exposure

In response to the critical need of more effective bio-dosimetric techniques to improve cancer risk estimation, this paper focuses on the design of an advanced biomedical instrumentation that could be used for radiation risk analysis on space missions. A designed concept for a hodoscope for radiation detection and tracking is tested via Monte Carlo simulation. The device consists of a set of layers of scintillating fibers, above and below a biological sample, in a design that allows for the determination of the direction of incoming and outgoing radiation. The efficiency of energy deposition on each of the different layers of the device is studied for proton radiation. The study of the response for different incoming energy is the main focus, but fiber-size is also a designed parameter considered in this study. The optimum energy range as found to be around 30 MeV’s – 50MeV’s depending on arrangement. It is found that energy deposited by protons in the optimum range in 1 mm-diameter fibers, is large enough for detection. Since smaller fibers allow for larger resolution, it is concluded that they are preferable than 2 mm fibers. Alternative arrangements consisting respectively of 3 and 4 layers of fibers on each side of the sample are tested and compared. It is observed that although one more coordinate for the source is needed, the 3-layers array is a viable alternative when that extra information is available. With this arrangement, the device is sensitive to lower energy photons.