Benzophenone and DNA: Evidence for a Double Insertion Mode and Its Spectral Signature

From explicit solvent molecular dynamics simulations, we probe the existence of two stable and competitive interaction modes between an alternating poly­(dA-dT) decamer and benzophenone, a minor groove adduct and a double insertion structure in which the central base pair is ejected, with hydrogen bonding with proximal groups, locking the DNA–drug complex. The extensive analysis of noncovalent interactions provides a rationale for the existence of this mode, never reported yet between DNA and any organic photosensitizer. We evidence a highly characteristic signature in our simulated circular dichroism spectra that may provide useful guidance for the future experimental efforts, as well as for theoretical investigations aiming at elucidating the energy-transfer mechanism between benzophenone and thymines

Interaction between <i>Yersinia pestis</i> Ail Outer Membrane Protein and the C‑Terminal Domain of Human Vitronectin

Yersinia pestis, the causative agent of plague, is capable of evading the human immune system response by recruiting the plasma circulating vitronectin proteins, which act as a shield and avoid its lysis. Vitronectin recruitment is mediated by its interaction with the bacterial transmembrane protein Ail, protruding from the Y. pestis outer membrane. By using all-atom long-scale molecular dynamic simulations of Ail embedded in a realistic model of the bacterial membrane, we have shown that vitronectin forms a stable complex, mediated by interactions between the disordered moieties of the two proteins. The main amino acids driving the complexation have also been evidenced, thus favoring the possible rational design of specific peptides which, by inhibiting vitronectin recruitment, could act as original antibacterial agents

New Insight into the Topology of Excited States through Detachment/Attachment Density Matrices-Based Centroids of Charge

In parallel with the derivation of a novel descriptor (ϕ_<i>S</i>) related to chromophores’ electronic excited states topology, the present article emphasizes some congruence of significance between our ϕ_<i>S</i> index and formerly developed centroid-related indices. We especially point out the possibility to formally adapt a barycenter (centroid) approach to the use of detachment/attachment densities. While the reciprocity of the two approaches can be mathematically evidenced, we will show that some difficulties brought by the use of ground and excited states electron densities in direct space can be overcome by undertaking some operations on the Hilbert space-related detachment/attachment matrices. We further wish to point out the crucial case of some chromophores holding two electron-withdrawing groups symmetrically disposed in a rod-like structure. Finally, we will qualitatively highlight the quadratic-like relationship between the amount of displaced charge induced by light absorption and the ϕ_<i>S</i> index

Toward a Quantitative Assessment of Electronic Transitions’ Charge-Transfer Character

We hereby report studies devoted to a topological descriptor of photoinduced electronic charge density variation. Our novel index, symbolized as ϕ_<i>S</i>, consists in the detachment and attachment densities overlap, where the detachment density physically depicts the electron density removed from the ground state of a molecule during the transition while the attachment density consists in the rearranged density in the excited state. Our method provides a simple and efficient way to quantitatively evaluate how easy the charge-separation is made upon the chromophore’s light absorption. Furthermore, this model can be applied for instance to address a comment on new push–pull dyes charge-transfer ability in order to assess their potentiality as candidates for light absorption-based devices. Moreover, the ϕ_<i>S</i> assessment allows us to perform some methodological diagnostic tests concerning the use of long-range corrected exchange–correlation functional in a time-dependent density functional theory (TDDFT) framework. This paper relates the ϕ_<i>S</i> descriptor’s mathematical foundations from various perspectives (detachment/attachment densities or natural transition orbitals), together with its application to several types of chromophores. Connections and divergences with a formerly proposed index are finally evidenced

Photophysical Properties of Novel Two-Photon Absorbing Dyes: Assessing Their Possible Use for Singlet Oxygen Generation

Herein, we assess the nonlinear absorption properties and the photophysical profile and behavior of two recently synthesized polythiophene-based dyes. In particular, using high level state-of-the-art molecular modeling methodologies, we clearly underline the remarkable two-photon absorption (TPA) cross-section. Furthermore, the possible pathways leading to the intersystem crossing and triplet manifold population are investigated by considering the energy difference between the relevant triplet and singlet states on the potential energy surfaces as the key critical points. The spin–orbit coupling is also assessed, and the results globally point to a possible, albeit probably slow, intersystem crossing that could allow the use of the two dyes as singlet oxygen photosensitizers, for instance in photodynamic therapy, owing to their high TPA cross-sections

Simulating the Electronic Circular Dichroism Spectra of Photoreversible Peptide Conformations

Electronic circular dichroism (CD) spectroscopy of peptides is one of the most important experimental characterization tools to get insights regarding their structure. Nevertheless, even though highly useful, the reliable simulations of CD spectra result in a complex task. Here, we propose a combination of quantum mechanics/molecular mechanics (QM/MM) methods with a semiempirical Hamiltonian based on the Frenkel excitons theory to efficiently describe the behavior of a model 27-amino acid α-helical peptide in water. Especially, we show how the choice of the QM region, including different possible hydrogen-bonding patterns, can substantially change the final CD spectrum shape. Moreover, we prove that our approach can correctly explain the changes observed in the peptide conformation (from α-helix to α-hairpin) when covalently linked to a protonated retinal-like molecular switch and exposing the system to UVA light, as previously observed by experiment and extensive molecular dynamics. Hence our protocol may be straightforwardly exploited to characterize light-induced conformation changes in photoactive materials and more generally protein folding processes

Detection of Nitroaromatic Explosives Based on Fluorescence Quenching of Silafluorene- and Silole-Containing Polymers: A Time-Dependent Density Functional Theory Study

Poly­(silafluorene-phenylenedivinylene)­s and poly­((tetraphenyl)-silole- phenylenedivinylene)­s are promising materials to be used as chemical sensors for explosives detection. The optoelectronic properties of these polymers as well as their constituent units have been investigated by modeling the properties of their excited states. Natural Transition Orbital analysis and topological ϕ_S descriptor assessment have been used to qualitatively and quantitatively characterize the physical nature of the transitions constituting the absorption spectra. The main transitions observed in all oligomers are associated to be a π–π* transition of the bridging moiety. Lower energy transitions of charge transfer character are further considered to understand the fluorescence quenching mechanism upon the complexation of these polymers with the analytes. Indeed the charge-transfer character of the first excited state leads to the emergence of thermal deactivation channels and hence to luminescence quenching

From Physical Mixtures to Co-Crystals: How the Coformers Can Modify Solubility and Biological Activity of Carbamazepine

A combined experimental and computational study on the solubility and biological activity of carbamazepine (CBZ), three co-crystals (COCs), and their parent physical mixtures (MIXs) is carried out to shed light onto the possible modulation of the drug properties. Two of the considered co-crystals, CBZ with vanillic acid (VAN) and CBZ with 4-nitropyridine <i>N</i>-oxide (NPO), are newly synthesized, while the third, CBZ with succinic acid (SUC), is already known. While COC CBZ-VAN and MIX CBZ-NPO did not alter the CBZ dissolution profile, MIX CBZ-SUC and COCs CBZ-SUC and CBZ-NPO inhibit straightaway its solubility. On the other hand, MIX CBZ-VAN induced a remarkable increase of the drug solubility. Analogously, different CBZ permeability values were registered following its dissolution from MIXs and COCs: CBZ and MIXs CBZ-SUC and CBZ-VAN slightly reduce the integrity of intestinal cell monolayers, whereas MIX CBZ-NPO and COCs CBZ-SUC, CBZ-VAN, and CBZ-NPO maintain the monolayer integrity. The molecular aggregates formed in solution were found to be the key to interpret these different behaviors, opening new possibilities in the pharmaceutical utilization and definition of drug co-crystals

Assessing One- and Two-Photon Optical Properties of Boron Containing Arenes

Linear and nonlinear optical properties of a series of bis­(<i>E</i>-dimesitylborylethenyl)-substituted arenes have been modeled by high-level computational protocols. The former compounds show a remarkable interest as infrared two-photon absorbers and hence may be used in the field of optical active and smart materials or for energy storage purposes. Excited state topologies, absorption and emission spectra, excited state metrics, natural transition orbitals and two-photon absorption cross-section of a series of chromophores have been computed by means of density functional theory (DFT) and time-dependent DFT (TD-DFT). An extended benchmark test on the performance of different functionals had been performed. Dynamic and vibronic effects on absorption and emission spectra have been taken into account by sampling the conformational space by means of Wigner distribution and the former have been evidenced as rather important in order to recover absorption maxima and spectral band shape. Important infrared two photon absorption cross sections involving transitions to the second excited state have been observed. In particular, thiophene bridges have been evidenced as the most beneficial to increase TPA efficiency leading to cross-section exceeding 1000 GM

Perturbation of Lipid Bilayers by Biomimetic Photoswitches Based on Cyclocurcumin

The use of photoswitches which may be activated by suitable electromagnetic radiation is an attractive alternative to conventional photodynamic therapy. Here, we report all-atom molecular dynamics simulation of a biomimetic photoswitch derived from cyclocurcumin and experiencing E/Z photoisomerization. In particular, we show that the two isomers interact persistently with a lipid bilayer modeling a cellular membrane. Furthermore, the interaction with the membrane is strongly dependent on the concentration, and a transition between ordered and disordered arrangements of the photoswitches is observed. We also confirm that the structural parameters of the bilayer are differently affected by the two isomers and hence can be modulated through photoswitching, offering interesting perspectives for future applications