Claudia Sandoval

Computationally efficient methodology for atomic-level characterization of dendrimer-drug complexes: A comparison of amine- and acetyl-terminated PAMAM

PAMAM dendrimers have been widely studied as a novel means for controlled drug delivery; however, computational study of dendrimer-drug complexation is made difficult by the conformational flexibility of dendrimers and the nonspecific nature of the dendrimer-drug interactions. Conventional protocols for studying drug binding have been designed primarily for protein substrates, and, therefore, there is a need to establish new protocols to deal with the unique aspects of dendrimers. In this work, we generate cavities in generation-5 polyamidoamine (PAMAM) dendrimers at selected distances from the center of mass of the dendrimer for the insertion of the model drug: dexamethasone 21-phosphate or Dp21. The complexes are then allowed to equilibrate with distance between centers of mass of the drug and dendrimers confined to selected ranges; the free energy of complexation is estimated by the MM-GBSA (MM, molecular mechanics; GB, generalized Born; SA, surface area) method. For both amine- and modified acetyl-terminated PAMAM at both low and neutral pH, the most favorable free energy of complexation is associated with Dp21 at distance of 15-20 Å from the center of mass of the dendrimer and that smaller or larger distances yield considerably weaker affinity. In agreement with experimental results, we find acetyl-terminated PAMAM at neutral pH to form the least stable complex with Dp21. The greatest affinity is seen in the case of acetyl-terminated PAMAM at low pH, which appears to be due a complex balance of different contributions, which cannot be attributed to electrostatics, van der Waals interactions, hydrogen bonds, or charge-charge interactions alone.

In situ and in silico evaluation of amine- and folate-terminated dendrimers as nanocarriers of anesthetics

The search for new nano-systems for targeted biomedical applications and controlled drug release has attracted significant attention in polymer chemistry, pharmaceutics, and biomaterial science. Controlled drug delivery has many advantages over conventional drug administration, such as reduction of side effects, maintaining a stable plasma level concentration and improving the quality of life of patients. In this study, PAMAM G5 dendrimers and PAMAM G5-folic acid conjugates (PAMAM G5-FA) are synthesized and characterized by mass spectrometry (MALDI-MS). Controlled release studies at different pH values show that PAMAM G5-FA is a good candidate as a carrier for tramadol and morphine, while mathematical modeling is conducted, suggesting that the release process is governed by a diffusion mechanism. In addition, using molecular dynamics simulations, we investigate the structural and energetic properties that facilitate the encapsulation of tramadol and morphine by unmodified and functionalized PAMAM-G5 dendrimers at low, neutral and high pH. Our results correlate well with experimental data, confirming that tramadol and morphine may be encapsulated both by functionalized PAMAM dendrimers and unmodified PAMAM. Moreover, the simulations further reveal that hydrogen-bond and electrostatic interactions govern the affinity the dendrimers for both drugs. This information is envisioned to prove useful for the encapsulation of other drugs and for the design of novel functionalized dendrimers.

Nanoinformatics: An emerging area of information technology at the intersection of bioinformatics, computational chemistry and nanobiotechnology

After the progress made during the genomics era, bioinformatics was tasked with supporting the flow of information generated by nanobiotechnology efforts. This challenge requires adapting classical bioinformatic and computational chemistry tools to store, standardize, analyze, and visualize nanobiotechnological information. Thus, old and new bioinformatic and computational chemistry tools have been merged into a new sub-discipline: nanoinformatics. This review takes a second look at the development of this new and exciting area as seen from the perspective of the evolution of nanobiotechnology applied to the life sciences. The knowledge obtained at the nano-scale level implies answers to new questions and the development of new concepts in different fields. The rapid convergence of technologies around nanobiotechnologies has spun off collaborative networks and web platforms created for sharing and discussing the knowledge generated in nanobiotechnology. The implementation of new database schemes suitable for storage, processing and integrating physical, chemical, and biological properties of nanoparticles will be a key element in achieving the promises in this convergent field. In this work, we will review some applications of nanobiotechnology to life sciences in generating new requirements for diverse scientific fields, such as bioinformatics and computational chemistry.

Solute–Solvent Interactions of Flavonoids in Organic Solvents

The diffusion coefficients of one flavone and five isoflavones in methanol, ethanol, 2-propanol, and acetonitrile were measured at 25°C by the Taylor–Aris dispersion method. The observed variations of the D values were interpreted in terms of solute–solvent hydrogen-bond interactions and the interpretation was supported by molecular dynamics simulations of two solutes in methanol.

Poly(ester)s Containing Germanium and Silicon in the Main Chain. 1. Langmuir Monolayer Characterization

Surface characterization of poly(ester)s containing germanium (Ge) or silicon (Si) in the main chain was studied. Surface pressure‐area isotherms (π‐A) at the air/water interface were obtained by monolayer compression at constant temperature. The molecular areas from the pressure‐area isotherms were estimated for all polymers. At low surface concentrations poly(ester)s the characterization of monolayers was carried out according to the variation of the surface pressure as a function of the surface concentration; the behavior observed was described by the virial expansion development. In the semidilute region, the surface pressure variation was expressed according to the scaling laws as a power function of the surface concentration. It was found that the chemical structure of the poly(ester)s studied influences the type of the isotherms. The morphology of the monolayers was observed by Brewster angle microscopy (BAM). The molecular mechanics approach was used to obtain predictions about the local interaction energies between segments and to explain the minimum area values at the collapse point.

Synthesis and Characterization of a Branched Poly(Methacrylamide): Thermal Stability and Molecular Simulation Studies of Their Blends With Vinylic Polymers

The synthesis of a poly(diethylaminoethyl methacrylamide) (BP), based on a lineal methacrylamide with diethylaminoethyl branches was carried out. Thermal behavior was studied by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). Relatively high thermal stability is found. Blends with poly(methylmethacrylate) (PMMA), poly(acrylic acid) (PAA) and poly(monomethyl itaconate) (PMMI) were prepared. Their thermal properties in blends were studied together with miscibility, in order to improve thermal properties of vinylic polymer blends. An increase of thermal stability was found for certain blend compositions. By FTIR analysis, higher band displacements were found for low BP compositions. AFM and molecular simulation analysis were carried out in order to elucidate the structural origin leading to thermal stability and miscibility increases. Hydrophobic interactions among methyl end groups of BP and methylene groups of vinylic polymers should be the responsible of miscibility and thermal stability increases.

Polymers containing phtalimidoalkyl groups in the side chains. effect of the alkyl groups in monolayers at the airwater interface

Abstract Surface activity of poly(methacrylate)s containing phthalimidoalkyl groups was studied. Surface pressure-area isotherms ( -A) at the air-water interface were determined. These polymers form stable and condensed monolayers. The monolayers are more condensed and the limiting surface area A0 values decrease when the number of the methylene groups in the lateral chains increases. Surface pressure variation at the semidilute region of the monolayers was expressed in terms of the scaling laws as power function of the surface concentration. The static elasticity εo and the exponent of the excluded volume υ were determined. The hydrophobicity degree of polymers was estimated from the determination of the total surface free energy values by wettability measurements. Molecular dynamic simulation (MDS) was performed in order to explain the experimental behavior of polymers at the air-water interface.