Stable Quasi-Solid-State Dye-Sensitized Solar Cells Using Novel Low Molecular Mass Organogelators and Room-Temperature Molten Salts

Stable quasi-solid-state dye-sensitized solar cells (DSCs) were fabricated by using room-temperature molten salts (1-methyl-3-hexyl-imidazolium iodide), and a series of diamine derivatives with different lengths of alkyl chain as low molecular mass organogelators (LMOGs). The number of methylene (−CH₂−) units between the two amide carbonyl groups in the gelator molecule has significant influence on the charge transport property of gel electrolyte, and the kinetic processes of the electron transport and recombination. Less compact networks of the ionic liquid gel electrolytes containing odd-numbered −CH₂– gelator facilitate the diffusion of I₃^– and I^–. Also, the odd-numbered −CH₂– gelators-based DSCs exhibit longer electron recombination lifetime and a higher open circuit potential (<i>V</i>_oc) compared with the DSCs based on even-numbered −CH₂– gelators; consequently, the photovoltaic performances of DSCs based on odd-numbered −CH₂– gelators are much better than those even-numbered −CH₂– gelators. Remarkably, the results of the accelerated aging tests showed that the ionic liquid gel electrolyte-based DSCs could retain 93%–99% of their initial photoelectric conversion efficiencies (η) under heat at 60 °C, and 100% of their initial photoelectric conversion efficiencies under one sun light soaking with UV cutoff filter at 50 °C for 1000 h. This excellent long-term stability of quasi-solid-state DSCs is very important for application and commercialization of DSCs

Discovery of Thiophene[3,2‑<i>d</i>]pyrimidine Derivatives as Potent HIV‑1 NNRTIs Targeting the Tolerant Region I of NNIBP

Our previous studies led us to conclude that thiophene­[3,2-<i>d</i>]­pyrimidine is a promising scaffold for diarylpyrimidine (DAPY)-type anti-HIV agents with potent activity against resistance-associated human immunodeficiency virus (HIV) variants (<i>J. Med. Chem</i>. <b>2016</b>, <i>59</i>, 7991–8007; <i>J. Med. Chem</i>. <b>2017</b>, <i>60</i>, 4424–4443). In the present study, we designed and synthesized a series of thiophenepyrimidine derivatives with various substituents in the right wing region of the structure with the aim of developing new interactions with the tolerant region I of the binding pocket of the HIV-1 non-nucleoside reverse transcriptase (NNRTI), and we evaluated their activity against a panel of mutant HIV-1 strains. All the derivatives exhibited moderate to excellent potency against wild-type (WT) HIV-1 in MT-4 cells. Among them, sulfonamide compounds <b>9b</b> and <b>9d</b> were single-figure-nanomolar inhibitors with EC₅₀ values of 9.2 and 7.1 nM, respectively. Indeed, <b>9a</b> and <b>9d</b> were effective against the whole viral panel except RES056. Notably, both compounds showed potent antiviral activity against K103N (EC₅₀ = 0.032 and 0.070 μM) and E138K (EC₅₀ = 0.035 and 0.045 μM, respectively). Furthermore, <b>9a</b> and <b>9d</b> exhibited high affinity for WT HIV-1 RT (IC₅₀ = 1.041 and 1.138 μM, respectively) and acted as classical NNRT inhibitors (NNRTIs). These results are expected to be helpful in the design of thiophenepyrimidine-based NNRTIs with more potent activity against HIV strains with RT mutations

Discovery of Novel Diarylpyrimidine Derivatives as Potent HIV‑1 NNRTIs Targeting the “NNRTI Adjacent” Binding Site

A novel series of diarylpyrimidine derivatives, which could simultaneously occupy the classical NNRTIs binding pocket (NNIBP) and the newly reported “NNRTI Adjacent” binding site, were designed, synthesized, and evaluated for their antiviral activities in MT-4 cell cultures. The results demonstrated that six compounds (<b>20</b>, <b>27</b> and <b>31</b>–<b>34</b>) showed excellent activities against wild-type (WT) HIV-1 strain (EC₅₀ = 2.4–3.8 nM), which were more potent than that of ETV (EC₅₀ = 4.0 nM). Furthermore, <b>20</b>, <b>27</b>, <b>33</b>, and <b>34</b> showed more potent or equipotent activity against single mutant HIV-1 strains compared to that of ETV. Especially, <b>20</b> showed marked antiviral activity, which was 1.5-fold greater against WT and 1.5- to 3-fold greater against L100I, K103N, Y181C, Y188L, and E138K when compared with ETV. In addition, all compounds showed lower toxicity (CC₅₀ = 5.1–149.2 μM) than ETV (CC₅₀ = 2.2 μM). The HIV-1 RT inhibitory assay was further conducted to confirm their binding target. Preliminary structure–activity relationships (SARs), molecular modeling, and calculated physicochemical properties of selected compounds were also discussed comprehensively

Structure-Based Optimization of Thiophene[3,2‑<i>d</i>]pyrimidine Derivatives as Potent HIV‑1 Non-nucleoside Reverse Transcriptase Inhibitors with Improved Potency against Resistance-Associated Variants

This work follows on from our initial discovery of a series of piperidine-substituted thiophene­[3,2-<i>d</i>]­pyrimidine HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTI) (J. Med. Chem. 2016, 59, 7991−8007). In the present study, we designed, synthesized, and biologically tested several series of new derivatives in order to investigate previously unexplored chemical space. Some of the synthesized compounds displayed single-digit nanomolar anti-HIV potencies against wild-type (WT) virus and a panel of NNRTI-resistant mutant viruses in MT-4 cells. Compound <b>25a</b> was exceptionally potent against the whole viral panel, affording 3-4-fold enhancement of in vitro antiviral potency against WT, L100I, K103N, Y181C, Y188L, E138K, and K103N+Y181C and 10-fold enhancement against F227L+V106A relative to the reference drug etravirine (ETV) in the same cellular assay. The structure–activity relationships, pharmacokinetics, acute toxicity, and cardiotoxicity were also examined. Overall, the results indicate that <b>25a</b> is a promising new drug candidate for treatment of HIV-1 infection

Structure-Based Optimization of Thiophene[3,2‑<i>d</i>]pyrimidine Derivatives as Potent HIV‑1 Non-nucleoside Reverse Transcriptase Inhibitors with Improved Potency against Resistance-Associated Variants

This work follows on from our initial discovery of a series of piperidine-substituted thiophene­[3,2-<i>d</i>]­pyrimidine HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTI) (J. Med. Chem. 2016, 59, 7991−8007). In the present study, we designed, synthesized, and biologically tested several series of new derivatives in order to investigate previously unexplored chemical space. Some of the synthesized compounds displayed single-digit nanomolar anti-HIV potencies against wild-type (WT) virus and a panel of NNRTI-resistant mutant viruses in MT-4 cells. Compound <b>25a</b> was exceptionally potent against the whole viral panel, affording 3-4-fold enhancement of in vitro antiviral potency against WT, L100I, K103N, Y181C, Y188L, E138K, and K103N+Y181C and 10-fold enhancement against F227L+V106A relative to the reference drug etravirine (ETV) in the same cellular assay. The structure–activity relationships, pharmacokinetics, acute toxicity, and cardiotoxicity were also examined. Overall, the results indicate that <b>25a</b> is a promising new drug candidate for treatment of HIV-1 infection

Further Exploring Solvent-Exposed Tolerant Regions of Allosteric Binding Pocket for Novel HIV‑1 NNRTIs Discovery

Based on the detailed analysis of the binding mode of diarylpyrimidines (DAPYs) with HIV-1 RT, we designed several subseries of novel NNRTIs, with the aim to probe biologically relevant chemical space of solvent-exposed tolerant regions in NNRTIs binding pocket (NNIBP). The most potent compound <b>21a</b> exhibited significant activity against the whole viral panel, being about 1.5–2.6-fold (WT, EC₅₀ = 2.44 nM; L100I, EC₅₀ = 4.24 nM; Y181C, EC₅₀ = 4.80 nM; F227L + V106A, EC₅₀ = 17.8 nM) and 4–5-fold (K103N, EC₅₀ = 1.03 nM; Y188L, EC₅₀ = 7.16 nM; E138K, EC₅₀ = 3.95 nM) more potent than the reference drug ETV. Furthermore, molecular simulation was conducted to understand the binding mode of interactions of these novel NNRTIs and to provide insights for the next optimization studies