José M. Granadino-Roldán

Recognition and discrimination of DNA quadruplexes by acridine-peptide conjugates

We have explored a series of trisubstituted acridine-peptide conjugates for their ability to recognize and discriminate between DNA quadruplexes derived from the human telomere, and the c-kit and N-ras proto-oncogenes. Quadruplex affinity was measured as the peptide sequences were varied, together with their substitution position on the acridine, and the identity of the C-terminus (acid or amide). Surface plasmon resonance measurements revealed that all compounds bound to the human telomeric quadruplex with sub-micromolar affinity. Docking calculations from molecular modelling studies were used to model the effects of substituent orientation and peptide sequence. Modelling and experiment were in agreement that placement of the peptide over the face of the acridine is detrimental to binding affinity. The highest degrees of selectivity were observed towards the N-ras quadruplex by compounds capable of forming simultaneous contacts with their acridine and peptide moieties. The ligands that bound best displayed quadruplex affinities in the 1-5 nM range and at least 10-fold discrimination between the quadruplexes studied.

Density functional theory study of the optical and electronic properties of oligomers based on phenyl-ethynyl units linked to triazole, thiadiazole, and oxadiazole rings to be used in molecular electronics

In the present work, we have studied from a theoretical perspective the geometry and electronic properties of the series of related compounds 2,5-bis(phenylethynyl)-1,3,4-thiadiazole, 2,5-bis(phenylethynyl)-1,3,4-oxadiazole, and 2,5-bis(phenylethynyl)-1,2,4-triazole as candidates for electron-conducting polymers and compounds with desirable (opto)electronic properties. The effect of the ethynyl group (-C[Triple Bond]C-) on the structure and electronic properties was also studied. The influence of planarity on electrical conductivity has been studied by a natural-bond-orbital analysis. The (opto)electronic properties and conducting capability were investigated through the highest occupied molecular orbital (HOMO)-lowest unoccupied molecular orbital (LUMO) gap, excitation energy, bond length alternation, LUMO energy, electron affinities, and intramolecular reorganization energy. Finally, the evolution of some properties such as optical bandgap and electron affinity with the increase of the number of repeat units in the oligomer chain has been checked.

Theoretical study of the effect of ethynyl group on the structure and electrical properties of phenyl-thiadiazole systems as precursors of electron-conducting materials

2,5-Bis(phenylethynyl)-1,3,4-thiadiazole (PhEtTh) and 2,5-diphenyl-1,3,4-thiadiazole (PhTh) are expected to be building blocks for polymer materials that could be employed to conduct electricity due to their narrow highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) energy gaps. In this work, a theoretical, comparative study about the effect of the ethynyl group on the planarity and electrical conductivity of this kind of systems has been carried out. Thus, several ab initio (Hartree-Fock, Moller-Plesset) and DFT (B3LYP, B3PW91, M05, M05-2X) methods and basis sets (6-31G(*), 6-31G+G(**), 6-311G(**), cc-pVDZ, cc-pVTZ) have been tested. As a result, PhEtTh showed better properties for its use as electric conducting material relative to PhTh due to its smaller HOMO-LUMO gap, as well as its enhanced trend to retain the planarity provided the reduction in steric hindrances that the ethynyl group (-C[triple bond]C-) permits. Solvent effects were also modeled for ethanol and chloroform under the conductor-like polarizable continuum model approximation. Finally, electronic transitions in gas and solution phases were predicted by using TDDFT approximation in order to compare the theoretical lambda(max) with the experimental values reported in literature for both compounds.

Protein–protein recognition as a first step towards the inhibition of XIAP and Survivin anti-apoptotic proteins

Apoptosis, also called programmed cell death, is a conserved mechanism inherent to all cells that sentences them to death when they receive the appropriate external stimuli. Inhibitor of apoptosis proteins (IAPs) are a family of regulatory proteins that suppress such cell death. XIAP is the most commonly studied member of the IAP family. It binds to and inhibits Caspases, an important family of apoptotic proteases. In addition, XIAP over‐expression has been detected in numerous types of cancer. Smac/DIABLO, a mitochondrial protein that binds to IAPs and promotes Caspase activation, has the opposite action to XIAP and can be considered a key protein in the regulation of IAPs. Survivin, the smallest IAP protein, has received a lot of attention due to its specific expression in many cancer cell lines. It has been shown to interact with Smac/DIABLO, even though the structure of this complex has not yet been reported.

Molecular conductivity switching of two benzene rings under electric field

A molecular transistor based on torsion-angle conformation change driven by gate electric field is designed and studied using ab initio calculations. This transistor consists of a SH–C6H2F(CH3)C6H2(CH3)F–SH molecule sandwiched between two Au(111) electrodes, where the interaction between the molecular dipole and a gate voltage induced electric field will cause the molecule to twist along its c-axis, changing the quantum conductivity of the molecule. The effect of thermal fluctuation on the molecular conformation is studied, so is the ability of the transistor to shut off its current. The advantages and challenges of using such molecular conformation change as a mechanism for transistor gating are discussed.

The vibrational analysis of styrene, revisited

Abstract In this report we present a new proposal of vibrational analysis for the styrene molecule on the basis of an a priori scaled force field and a comparison between calculated infrared intensities and experimental absorbances. This has been done in order to clarify some discrepancies appearing in previous assignments for ν27,ν31,ν32,ν34 and ν38 modes. As experimental data we have used new IR and Raman spectra recorded at room temperature. The force field has been built up using as scale factors the arithmetic mean of those obtained for 3-fluoro, 4-fluoro, 3-chloro and 4-chlorostyrene. The root-mean-square deviation (rms) between experimental and calculated wave numbers turns out to be 6.7 cm−1, which demonstrates the reliability of the methodology used.

A Tuned LRC-DFT Design of Ambipolar Diketopyrrolopyrrole- Containing Quinoidal Molecules Interesting for Molecular Electronics

This work presents a Density Functional Theory (DFT) study on the charge transport related properties of two quinoidal diketopyrrolopyrrole (DPP) based systems. System A, recently synthesized, shows high efficiency as n-type organic semiconductor material while system B, not synthesized yet, has a linking benzothiadiazole (BT) unit between DPP moieties and would display an ambipolar character. The use of tuned, long-range corrected (LRC) functionals allows one to predict HOMO, LUMO, and charge transport properties for compound A in concordance with those experimentally observed. The use of BT building blocks allows for a conclusion that compound B is expected to display balanced and efficient charge injection along with high mobilities both for holes and electrons, which points to its potential to obtain high performances as an ambipolar semiconductor.

The role of disorder on the electronic structure of conjugated polymers. The case of poly-2,5-bis(phenylethynyl)-1,3,4-thiadiazole

Insight into the electronic structure of disordered poly-2,5-bis(phenylethynyl)-1,3,4-thiadiazole in an amorphous region, in comparison to an ideal two-planar cofacial oligomer system, is pursued. The atomic structure of the amorphous polymer was obtained from classical molecular dynamics. It was subsequently used to calculate the electronic states and inter- and intrachain electronic coupling integrals using the density functional theory based charge patching method. The interchain electronic coupling integrals in the amorphous system were found to be an order of magnitude smaller than in the ordered system with similar distances between the chains. The results also suggest that the electronic structure of the whole system cannot be understood as a collection of the electronic structures of individual chains. The band gap of the whole system is significantly smaller than the band gaps of individual chains. This decrease originates from the disordered long range electrostatic potential created by the dipole moments of polymer repeat units, which should be minimized if one seeks good transport properties.

DFT study of the effect of fluorine atoms on the crystal structure and semiconducting properties of poly(arylene-ethynylene) derivatives.

The effect of fluorine substitution on the molecular structure, crystal packing, and n-type semiconducting properties of a set of poly(arylene-ethynylene) polymers based on alternating thiadiazole and phenyl units linked through ethynylene groups has been studied by means of Density Functional Theory. As a result, an enlargement in the interplanar distance between cofacial polymer chains, as well as a decrease of the electronic coupling and electron mobility is predicted. On the other hand, fluorination could facilitate electron injection into the material. A polymer containing both alkoxy pendant chains and fluorine atoms is proposed as a compromise solution between efficiency of electron injection and charge transport within the material.

Crystal structure and charge transport properties of poly(arylene-ethynylene) derivatives: A DFT approach

In the present study, a series of crystalline poly(arylene-ethynylene) copolymers containing phenylethynylene and 2,5-dialkoxy-phenylethynylene units together with 1,3,4-thiadiazole rings has been modeled by means of periodic calculations. Optimized three-dimensional polymeric structures show interchain distances that are consistent with the experimental values reported for a related polymer. It has also been observed that the presence of pendant alkoxy chains brings on both a further flattening and a separation of the coplanar chains. This fact is linked to a decrease of the interchain cofacial distance. The electron transport character of the polymer crystal structures was assessed through Marcus theory. Electronic coupling between neighboring polymer chains is most influenced by the presence of alkoxy chains giving rise to an expectable enhancement of the electron hopping mobility.