Antibodies as Carrier Molecules: Encapsulating Anti-Inflammatory Drugs inside Herceptine

The human epidermal growth factor receptor 2 (HER2) is overexpressed in about a third of breast cancer patients, with a strong involvement of the cyclooxygenase-2 (COX-2) enzyme in the tumor progress. HER2 and COX-2 are consequently potential targets for inhibiting carcionogenesis. Herceptin (trastuzumab) is an antibody that partially blocks HER2-positive cancers at their initial stage. Unfortunately, the overall response rate to the single treatment with this antibody is still modest, and therefore, it needs to be improved by combining several chemotherapeutic agents. On the other hand, nonsteroidal anti-inflammatory drugs (NSAIDs) are designed to halt COX-2 functionality, so they might also exhort an anticancer activity. In this contribution, dual Herceptin–NSAID drugs are designed using theoretical tools. More specifically, blind docking, molecular dynamics, and quantum calculations are performed to assess the stability of 14 NSAIDs embedded inside Herceptin. Our calculations reveal the feasibility of improving the antitumor activity of the parent Herceptin by designing a dual HER2-targeting with Etofenamate. That coupling mode might be used to further rationalize new clinical strategies beyond classical antibody dosages

Structure–Property Correlation behind the High Mobility of Carbazolocarbazole

A comparative study of carbazolocarbazole isomers and their respective <i>N</i>-alkyl derivatives confirms the good performance of carbazolo­[2,1-<i>a</i>]­carbazole as hole-transporting material in organic field effect transistors. The azaphenacene structure of this molecule forms a dense packing promoted by particularly short longitudinal shifts between molecules establishing face-to-face and edge-to-face interactions. Computational calculations have determined an almost isotropic 2D transport environment within a lamellar structure. This favorable solid state arrangement, in combination with appropriate interfacial layers, has led to a high mobility (1.3 cm² V^–1 s^–1) that validates the aptitude of this molecular material as an organic semiconductor

DFT Simulation of Structural and Optical Properties of 9‑Aminoacridine Half-Sandwich Ru(II), Rh(III), and Ir(III) Antitumoral Complexes and Their Interaction with DNA

In this work, we use DFT-based methods to simulate the chemical structures, optical properties, and interaction with DNA of a recently synthesized chelated C^N 9-aminoacridine arene Ru­(II) anticancer agent and two new closely related Rh­(III) and Ir­(III) complexes using DFT-based methods. Four chemical models and a number of theoretical approaches, which representatively include the PBE0, B97D, ωB97X, ωB97X-D, M06, and M06-L density functionals and the LANL2DZ, def2-SVP, and def2-TZVP basis sets, are tested. The best overall accuracy/cost performance for the optimization process is reached at the ωB97X-D/def2-SVP and M06/def2-SVP levels of theory. Inclusion of explicit solvent molecules (CHCl₃) further refines the geometry, while taking into account the crystal network gives no significant improvements of the computed bond distances and angles. The analysis of the excited states reveals that the M06 level matches better the experimental absorption spectra, compared to ωB97X-D. The use of the M06/def2-SVP approach is therefore a well-balanced method to study theoretically the bioactivity of this type of antitumoral complexes, so we couple this TD-DFT approach to molecular dynamics simulations in order to assess their reactivity with DNA. The reported results demonstrate that these drugs could be used to inject electrons into DNA, which might broaden their applications in photoactivated chemotherapy and as new materials for DNA-based electrochemical nanodevices

DFT Simulation of Structural and Optical Properties of 9‑Aminoacridine Half-Sandwich Ru(II), Rh(III), and Ir(III) Antitumoral Complexes and Their Interaction with DNA

In this work, we use DFT-based methods to simulate the chemical structures, optical properties, and interaction with DNA of a recently synthesized chelated C^N 9-aminoacridine arene Ru­(II) anticancer agent and two new closely related Rh­(III) and Ir­(III) complexes using DFT-based methods. Four chemical models and a number of theoretical approaches, which representatively include the PBE0, B97D, ωB97X, ωB97X-D, M06, and M06-L density functionals and the LANL2DZ, def2-SVP, and def2-TZVP basis sets, are tested. The best overall accuracy/cost performance for the optimization process is reached at the ωB97X-D/def2-SVP and M06/def2-SVP levels of theory. Inclusion of explicit solvent molecules (CHCl₃) further refines the geometry, while taking into account the crystal network gives no significant improvements of the computed bond distances and angles. The analysis of the excited states reveals that the M06 level matches better the experimental absorption spectra, compared to ωB97X-D. The use of the M06/def2-SVP approach is therefore a well-balanced method to study theoretically the bioactivity of this type of antitumoral complexes, so we couple this TD-DFT approach to molecular dynamics simulations in order to assess their reactivity with DNA. The reported results demonstrate that these drugs could be used to inject electrons into DNA, which might broaden their applications in photoactivated chemotherapy and as new materials for DNA-based electrochemical nanodevices

Hydrogen Bond-Directed Cruciform and Stacked Packing of a Pyrrole-Based Azaphenacene

Solid state packing plays a critical role in molecular materials to be applied within the area of organic electronics since the arrangement of molecules conditions the quality of the charge transport. Due to the difficulty in accurately predicting the crystal packing simply from the molecular structure, the design of molecules which can self-organize using strategically located functional groups becomes a useful approach to induce certain order directed by noncovalent interactions. The orientation of these interactions can be intentionally controlled from the early stage of molecular design and contribute to restrict the randomness of molecular arrangement in the solid state. Herein, we describe the synthesis and solid state characterization of a novel fused polyheteroaromatic system incorporating hydrogen bond donor and acceptor sites directly into a pentacyclic structure without disrupting its conjugation. A comparative study with an analogous system without hydrogen bond acceptor sites shows the remarkable effect of the hydrogen bond-directed assembly on the crystal packing and the benefits on the π–π intermolecular overlap, crucial for charge transport processes in organic semiconductors