Molecular Design Platform Research Articles

Modular Design Platform for Activatable Fluorescence Probes Targeting Carboxypeptidases Based on ProTide Chemistry.

Carboxypeptidases (CPs) are a family of hydrolases that cleave one or more amino acids from the C-terminal of peptides or proteins and play indispensable roles in various physiological and pathological processes. However, only a few highly activatable fluorescence probes for CPs have been reported, and there is a need for a flexibly tunable molecular design platform to afford a range of fluorescence probes for CPs for biological and medical research. Here, we focused on the unique activation mechanism of ProTide-based prodrugs and established a modular design platform for CP-targeting florescence probes based on ProTide chemistry. In this design, probe properties such as fluorescence emission wavelength, reactivity/stability, and target CP can be readily tuned and optimized by changing the four probe modules: the fluorophore, the substituent on the phosphorus atom, the linker amino acid at the P1 position, and the substrate amino acid at the P1' position. In particular, switching the linker amino acid at position P1 enabled us to precisely optimize the reactivity for target CPs. As a proof-of-concept, we constructed probes for carboxypeptidase M (CPM) and prostate-specific membrane antigen (also known as glutamate carboxypeptidase II). The developed probes were applicable for the imaging of CP activities in live cells and in clinical specimens from patients. This design strategy should be useful in studying CP-related biological and pathological phenomena.

Engineering J-aggregates for NIR-induced meso-CF3-BODIPY nanoparticles by activated apoptosis mechanism in photothermal therapy

Forming J-aggregates by organic monomer is a fascinating strategy to urge spectroscopic redshift with respect to that of the monomer. Herein, we designed 1,7-diphenyl-substituted meso‑CF3-BDP monomer confirmed by X-ray crystallographic analysis. The low-barrier rotation of the –CF3 group in meso‑CF3-BDP 1 significantly enhances the non-radiative efficiency, and the photothermal conversion efficiency (PCE) of the self-assembled nanoparticles (1-NPs: λabs = 746 nm) by J-aggregates was 82%. 1-NPs could effectively block cell cycle progression, inhibit cancer cell proliferation and trigger cell apoptosis under low power laser irradiation (0.2 W/cm2). This study proposes an alternate molecular design platform by J-aggregates to promote PCE through the insertion of rotating segment and trigger the cancer cells apoptosis in photothermal therapy at low power laser density.

Assessing Molecular Docking Tools to Guide the Design of Polymeric Materials Formulations: A Case Study of Canola and Soybean Protein.

After more than 40 years of biopolymer development, the current research is still based on conventional laboratory techniques, which require a large number of experiments. Therefore, finding new research methods are required to accelerate and power the future of biopolymeric development. In this study, promising biopolymer–additive ranking was described using an integrated computer-aided molecular design platform. In this perspective, a set of 21 different additives with plant canola and soy proteins were initially examined by predicting the molecular interactions scores and mode of molecule interactions within the binding site using AutoDock Vina, Molecular Operating Environment (MOE), and Molecular Mechanics/Generalized Born Surface Area (MM-GBSA). The findings of the investigated additives highlighted differences in their binding energy, binding sites, pockets, types, and distance of bonds formed that play crucial roles in protein–additive interactions. Therefore, the molecular docking approach can be used to rank the optimal additive among a set of candidates by predicting their binding affinities. Furthermore, specific molecular-level insights behind protein–additives interactions were provided to explain the ranking results. The highlighted results can provide a set of guidelines for the design of high-performance polymeric materials at the molecular level. As a result, we suggest that the implementation of molecular modeling can serve as a fast and straightforward tool in protein-based bioplastics design, where the correct ranking of additives among sets of candidates is often emphasized. Moreover, these approaches may open new ways for the discovery of new additives and serve as a starting point for more in-depth investigations into this area.

Mechanically Triggered Release of Functionally Diverse Molecular Payloads from Masked 2-Furylcarbinol Derivatives.

Polymers that release functional small molecules in response to mechanical force are appealing targets for drug delivery, sensing, catalysis, and many other applications. Mechanically sensitive molecules called mechanophores are uniquely suited to enable molecular release with excellent selectivity and control, but mechanophore designs capable of releasing cargo with diverse chemical functionality are limited. Here, we describe a general and highly modular mechanophore platform based on masked 2-furylcarbinol derivatives that spontaneously decompose under mild conditions upon liberation via a mechanically triggered reaction, resulting in the release of a covalently installed molecular payload. We identify key structure–property relationships for the reactivity of 2-furylcarbinol derivatives that enable the mechanically triggered release of functionally diverse molecular cargo with release kinetics being tunable over several orders of magnitude. In particular, the incorporation of an electron-donating phenoxy group on the furan ring in combination with an α-methyl substituent dramatically lowers the activation barrier for fragmentation, providing a highly active substrate for molecular release. Moreover, we find that phenoxy substitution enhances the thermal stability of the mechanophore without adversely affecting its mechanochemical reactivity. The generality and efficacy of this molecular design platform are demonstrated using ultrasound-induced mechanical force to trigger the efficient release of a broad scope of cargo molecules, including those bearing alcohol, phenol, alkylamine, arylamine, carboxylic acid, and sulfonic acid functional groups.

A new molecular design platform for high-performance polymers from versatile bio-based tyramine: a case study of tyramine-derived phthalonitrile resin

Tyramine was first introduced into high-performance polymers as a promising monomer platform; the derived phthalonitrile resin exhibits excellent thermal stability and a high Tg value.

An excited state managing molecular design platform of blue thermally activated delayed fluorescence emitters by π-linker engineering

A molecular design platform of blue thermally activated delayed fluorescence (TADF) emitters to boost the external quantum efficiency and efficiency roll-off of blue TADF organic light-emitting diodes (OLEDs) was developed.

A prospective partial bio-based diamine-adenine-monomer platform for high performance polymer: A case study on phthalonitrile resin

A novel partial bio-based molecular design platform for high performance polymer (HPP) namely diamine-adenine-monomer platform (DAAMP) was suggested and discussed in this paper. Aimed at introducing the adenine moiety into backbone of HPP and endowing great wide molecular tailorability, DAAMP was synthesized via a nucleophilic displacement between 6-chloropurine and various diamines. Phthalonitrile (PN) resin is a typical class of HPP. To verify the feasibility of DAAMP for HPP design, two new phthalonitrile monomers based on two different diamine namely DAAMP-PN were synthesized. The chemical structures of synthesized monomers were confirmed by Fourier Transform Infrared spectroscopy (FTIR) and Nuclear Magnetic Resonance (NMR). The two new DAAMP-PNs based on different diamines showed an obvious difference in thermal polymerization behavior. Multiple hydrogen bonding was exhibited in DAAMP-PN system. And the prepared DAAMP-PN polymer showed high glass transition temperature, excellent thermal and thermo-oxidative stabilities. The results demonstrated that DAAMP is a promising building-block for HPP design with flexible molecular tailorability.

Metal–Organophosphine Framework‐Derived N,P‐Codoped Carbon‐Confined Cu3P Nanopaticles for Superb Na‐Ion Storage

AbstractMetal–organic framework derived approaches are emerging as a viable way to design carbon‐confined transitional metal phosphides (TMPs@C) for energy storage and conversion. However, their preparation generally involves a phosphorization using a large amount of additional P sources, which inevitably releases flammable, poisonous PH3. Therefore, developing an efficient strategy for eco‐friendly synthesis of TMPs@C is full of challenges. Here, a metal–organophosphine framework (MOPF) derived strategy is developed to allow an eco‐friendly design of TMPs@C without an additional P source, avoiding release of PH3. To illustrate this strategy, 1,3,5‐triaza‐7‐phosphaadamantane (PTA) ligands and Cu(NO3)2 metal centers are employed to construct Cu/PTA‐MOPFs nanosheets. Cu/PTA‐MOPFs can be directly converted to carbon‐confined Cu3P nanoparticles by annealing. Benefiting from high heteroatom content in PTA, a high doping content of 3.92 at% N and 8.26 at% P can also be achieved in the carbon matrix. As a proof‐of‐concept application, N,P‐codoped carbon‐confined Cu3P nanoparticles as anodes for Na‐ion storage exhibit a high initial reversible capacity of 332 mA h g−1 at 50 mA g−1, and superb rate and cyclic performance. Due to rich coordination modes of organophosphine, MOPFs are expected to become a promising molecular platform for design of various heteroatom‐doped TMPs@C for energy storage and conversion.

螺芴氧杂蒽(SFX)类有机半导体及其OLEDs

One-pot protocol to spiro-based organic semiconductors has several advantages such as low-cost stuffs available, pot-atom-step economic (PASE) procedures, and others over the conventional o -halobiaryl method, representing the paradigm of green organic semiconductors (GOS) with the application of information technology. Herein, this review traces back to the history of spiro-compounds, including synthesis, structures and the application of electronics, followed by the discovery on one-pot synthesis of spirocyclic arenes with the merit of tandem mechanism that involves three bonding at once. We demonstrated the SFX-based molecular design platform under the four-element theory to organic semiconductors, affording a chance to get insight into structure-parameter relationship. Finally, we highlighted the SFX-based electroluminescent materials, including various fluorescent materials, RGB phosphorescent host and guest materials as well as printable OLEDs materials. Among them, the best deep-blue fluorescent OLED exhibits the maximum current efficiency (CE), the maximum power efficiency (PE) and external quantum efficiency (EQE) of 7.4 cd/A, 4.1 lm/W, 4.6%, respectively; the obtained green phosphorescent OLED with the CE of 70.0 cd/A, PE of 77.0 lm/W, EQE of 19.2%, as well as universal host materials for phosphorescent OLEDs. Finally, we outlook the spiro-based GOSs, including the obstacle of synthetic methodology to spiro-arenes, application bottleneck for OLEDs display and lighting source, potential explorations in other electronics, molecular circuits as well as smart devices.

Molecular platform for design and synthesis of targeted dual-modality imaging probes.

We report a versatile dendritic structure based platform for construction of targeted dual-modality imaging probes. The platform contains multiple copies of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) branching out from a 1,4,7-triazacyclononane-N,N′,N″-triacetic acid (NOTA) core. The specific coordination chemistries of the NOTA and DOTA moieties offer specific loading of 68/67Ga3+ and Gd3+, respectively, into a common molecular scaffold. The platform also contains three amino groups which can potentiate targeted dual-modality imaging of PET/MRI or SPECT/MRI (PET: positron emission tomography; SPECT: single photon emission computed tomography; MRI: magnetic resonance imaging) when further functionalized by targeting vectors of interest. To validate this design concept, a bimetallic complex was synthesized with six peripheral Gd-DOTA units and one Ga-NOTA core at the center, whose ion T1 relaxivity per gadolinium atom was measured to be 15.99 mM–1 s–1 at 20 MHz. Further, the bimetallic agent demonstrated its anticipated in vivo stability, tissue distribution, and pharmacokinetic profile when labeled with 67Ga. When conjugated with a model targeting peptide sequence, the trivalent construct was able to visualize tumors in a mouse xenograft model by both PET and MRI via a single dose injection.

Thiacalix[4]arene as molecular platform for design of alkaline phosphatase inhibitors

Effect of thiacalix[4]arene platform on inhibition of alkaline phosphatase by macrocyclic phosphonate is presented in this article. Using tetrakis(dihydroxyphosphorylmethyl) derivatives we have found that phosphonate inhibitor on thiacalix[4]arene platform has displayed stronger inhibition properties towards alkaline phosphatases from bovine intestine mucosa, shrimp and human placenta than its structural calix[4]arene analogue. For elucidation of the molecular mechanism of the inhibition the tested macrocyclic compounds were docked computationally to the active site of alkaline phosphatase from shrimp. The role of thiacalix[4]arene platform in formation of the enzyme-inhibitor complex is discussed. Thiacalix[4]arene as molecular platform for design of alkaline phosphatase inhibitors