Design of new imidazole derivatives with anti-HCMV activity: QSAR modeling, synthesis and biological testing.

The problem of designing new antiviral drugs against Human Cytomegalovirus (HCMV) was addressed using the Online Chemical Modeling Environment (OCHEM). Data on compound antiviral activity to human organisms were collected from the literature and uploaded in the OCHEM database. The predictive ability of the regression models was tested through cross-validation, giving coefficient of determination q2 = 0.71-0.76. The validation of the models using an external test set proved that the models can be used to predict the activity of newly designed compounds with reasonable accuracy within the applicability domain (q2 = 0.70-0.74). The models were applied to screen a virtual chemical library of imidazole derivatives, which was designed to have antiviral activity. The six most promising compounds were identified, synthesized and their antiviral activities against HCMV were evaluated in vitro. However, only two of them showed some activity against the HCMV AD169 strain.

Second Generation G-Quadruplex Stabilizing Trimethine Cyanines.

G-Quadruplex DNA has been recognized as a highly appealing target for the development of new selective chemotherapeutics, which could result in markedly reduced toxicity toward normal cells. In particular, the cyanine dyes that bind selectively to G-quadruplex structures without targeting duplex DNA have attracted attention due to their high amenability to structural modifications that allows fine-tuning of their biomolecular interactions. We have previously reported pentamethine and symmetric trimethine cyanines designed to effectively bind G-quadruplexes through end stacking interactions. Herein, we are reporting a second generation of drug candidates, the asymmetric trimethine cyanines. These have been synthesized and evaluated for their quadruplex binding properties. Incorporating a benz[c,d]indolenine heterocyclic unit increased overall quadruplex binding, and elongating the alkyl length increases the quadruplex-to-duplex binding specificity.

Ultrafast Long-Range Charge Separation in Nonfullerene Organic Solar Cells.

Rapid, long-range charge separation in polymer-fullerene organic solar cells (OSCs) enables electrons and holes to move beyond their Coulomb capture radius and overcome geminate recombination. Understanding the nature of charge generation and recombination mechanisms in efficient, nonfullerene-acceptor-based OSCs are critical to further improve device performance. Here we report charge dynamics in an OSC using a perylene diimide (PDI) dimer acceptor. We use transient absorption spectroscopy to track the time evolution of electroabsorption caused by the dipolar electric field generated between electron-hole pairs as they separate after ionization at the donor-acceptor interface. We show that charges separate rapidly (<1 ps) and that free charge carriers are generated very efficiently (∼90% quantum yield). However, in the PDI-based OSC, external charge extraction is impaired by faster nongeminate decay to the ground state and to lower-lying triplet states.

Comparison of the Optical and Electrochemical Properties of Bi(perylene diimide)s Linked through Ortho and Bay Positions.

The Ullmann homocoupling of 2-bromo-perylene diimides (PDIs) gave [2,2'-biperylene]-3,4:9,10:3',4':9',10'-tetrakis(dicarboximide)s, 2,2'-bi(PDI)s, and the Suzuki coupling of a PDI-2-boronic ester and a 1-bromo-PDI gave a [1,2'-biperylene]-3,4:9,10:3',4':9',10'-tetrakis(dicarboximide), 1,2'-bi(PDI). These were compared with [1,1'-biperylene]-3,4:9,10:3',4':9',10'-tetrakis(dicarboximide)s, 1,1'-bi(PDI)s. Solution absorption spectra suggest that the PDIs in 2,2'-bi(PDI)s are more planar and less strongly coupled than those in 1,1'-bi(PDI)s, which is consistent with density functional theory calculations. 2,2'-Bi(PDI)s are less easily reduced than 1,1'- and 1,2'-bi(PDI)s by ca. 70-90 mV. Bulk heterojunction organic solar cells incorporating a 2,2'-bi(PDI) acceptor behaved similarly to those employing its 1,1'-bi(PDI) analogue.