Molecular Engineering Strategy Research Articles

Molecular engineering strategy and optoelectronic properties of diaminobenzene-thiazole π-conjugated small donor molecules for high-performance organic solar cells

In this current study, the π-conjugated oligomers based on Thiazole units have been designed to understand the interaction of molecular orbitals and the influence of the substituents on the energetic HOMO-LUMO gap to build highly π-conjugated nanostructures. Their strong π-conjugated insight was also evidenced in gas phase through the photovoltaic properties using B3LYP/6-31G(d,p) level of theory for potential applications in organic electronic devices. Our research indicates geometries optimized structures, FMOs and chemical parameters were determined to predict optical properties of all oligomers. The results demonstrate that thiazole unit’s addition improved absorption above 400 nm at first excited states. The open-cicruit voltage Voc have been decreased from 2.22 V to 1.26 V in M1-a to M1-d. Whereas, LHE values was increased from 0.404 to 0.986 in M2-a to M2-d. All designed molecules have shown the enhanced optoelectronic characteristic that is plausible reason for their potential photoactive use in Organic Photovoltaics (OPVs) devices efficiencies.

Advances in Bioinspired Artificial System Enabling Biomarker-Driven Therapy.

Bioinspired molecular engineering strategies have emerged as powerful tools that significantly enhance the development of novel therapeutics, improving efficacy, specificity, and safety in disease treatment. Recent advancements have focused on identifying and utilizing disease-associated biomarkers to optimize drug activity and address challenges inherent in traditional therapeutics, such as frequent drug administrations, poor patient adherence, and increased risk of adverse effects. In this review, we provide a comprehensive overview of the latest developments in bioinspired artificial systems (BAS) that use molecular engineering to tailor therapeutic responses to drugs in the presence of disease-specific biomarkers. We examine the transition from open-loop systems, which rely on external cues, to closed-loop feedback systems capable of autonomous self-regulation in response to disease-associated biomarkers. We detail various BAS modalities designed to achieve biomarker-driven therapy, including activatable prodrug molecules, smart drug delivery platforms, autonomous artificial cells, and synthetic receptor-based cell therapies, elucidating their operational principles and practical in vivo applications. Finally, we discuss the current challenges and future perspectives in the advancement of BAS-enabled technology and envision that ongoing advancements toward more programmable and customizable BAS-based therapeutics will significantly enhance precision medicine.

Covalent Organic Framework with Donor1‐Acceptor‐Donor2 Motifs Regulating Local Charge of Intercalated Single Cobalt Sites for Photocatalytic CO2 Reduction to Syngas

AbstractCovalent organic framework (COF) has attracted increasing interest in photocatalytic CO2 reduction, but it remains a challenge to achieve high conversion efficiency owing to the insufficient active site and fast charge recombination. Rationally optimizing the electronic structures of COF to regulate the local charge of active sites precisely is the key point to improving catalytic performance. Herein, intercalated single Co sites coordinated by imine‐N motifs have been designed by using trinuclear copper‐based imine‐COFs with distinct electronic moieties via a molecular engineering strategy. It is confirmed that the charge delivery property and local charge distribution of these heterometallic frameworks can be profoundly influenced by electronic structures. Among these featured structures with mixed‐state copper clusters, Co/Cu3‐TPA‐COF stands out for an exceptional photocatalytic CO2 reduction activity and tunable syngas (CO/H2) ratio by changing various bipyridines. Experimental and theoretical results indicate that interlayer Co‐imine N motifs on the donor1‐acceptor‐donor2 structures facilitate the formation of a highly separated electron‐hole state, which effectively induces the oriented electron transfer from dual electron donors to Co centers, achieving an enhanced CO2 activation and reduction. This work opens up an avenue for the design of high‐performance COF‐based catalysts for photocatalytic CO2 reduction.

Covalent Organic Framework with Donor1-Acceptor-Donor2 Motifs Regulating Local Charge of Intercalated Single Cobalt Sites for Photocatalytic CO2 Reduction to Syngas.

Covalent organic framework (COF) has attracted increasing interest in photocatalytic CO2 reduction, but it remains a challenge to achieve high conversion efficiency owing to the insufficient active site and fast charge recombination. Rationally optimizing the electronic structures of COF to regulate the local charge of active sites precisely is the key point to improving catalytic performance. Herein, intercalated single Co sites coordinated by imine-N motifs have been designed by using trinuclear copper-based imine-COFs with distinct electronic moieties via a molecular engineering strategy. It is confirmed that the charge delivery property and local charge distribution of these heterometallic frameworks can be profoundly influenced by electronic structures. Among these featured structures with mixed-state copper clusters, Co/Cu3-TPA-COF stands out for an exceptional photocatalytic CO2 reduction activity and tunable syngas (CO/H2) ratio by changing various bipyridines. Experimental and theoretical results indicate that interlayer Co-imine N motifs on the donor1-acceptor-donor2 structures facilitate the formation of a highly separated electron-hole state, which effectively induces the oriented electron transfer from dual electron donors to Co centers, achieving an enhanced CO2 activation and reduction. This work opens up an avenue for the design of high-performance COF-based catalysts for photocatalytic CO2 reduction.

Molecularly engineering a lipid nanoregulator destroying the last defense of ferroptosis in breast cancer therapy

Ferroptosis, as a uniquely regulated form of cell death, has garnered significant interest in the field of oncology. Most ferroptosis inducers facilitate the intracellular buildup of lipid peroxidation by inhibiting glutathione peroxidase 4 (GPX4). However, the high saturation level of membrane lipids can shield cancer cells from reactive oxygen species-induced damage, preventing lipid peroxidation triggered by GPX4 inhibitors. Herein, we precisely constructed a lipid nanoregulator of RSL3 and Orlistat through a molecular engineering strategy. In this nanosystem, Orlistat functions as a “dual enhancer”, significantly enhancing both the assembly capability and the anti-tumor effectiveness of RSL3. Orlistat can significantly enhance the synthesis of polyunsaturated fatty acids and reduce the saturation level of lipid membranes by inhibiting fatty acid synthase (FASN). Consequently, Orlistat successfully dismantles the final defense (lipid membrane protection), synergistically amplifying ferroptosis with RSL3-induced GPX4 depletion. As expected, the lipid nanoregulator demonstrates a potent antitumor activity in 4T1 tumor-bearing mice. This study represents an effective paradigm for ferroptosis-driven antitumor nanotherapeutics.

Steric hindrance shielding viologen against alkali attack in realizing ultrastable aqueous flow batteries

Viologens known as a kind of promising negolyte materials for aqueous organic redox flow batteries, face a critical stability challenge due to the SN2 nucleophilic attack by hydroxide ions (OH–) during the battery cycling. In this work, a N-cyclic quaternary ammonium-grafted viologen molecule, viz. 1,1′-bis(4,4′-dimethylpiperidiniumyl)-4,4′-bipyridinium tetrachloride ((DBPPy)Cl4), is developed by the molecular engineering strategy. The obtained (DBPPy)Cl4 molecule shows a decent solubility of 1.84 M and a redox potential of −0.52 V vs. Ag/AgCl. Experimental and theoretical results reveal that the grafted N-cyclic quaternary ammonium groups act as the steric hindrance to prevent nucleophilic attack by OH–, increasing the alkali resistance of the electroactive molecule. The symmetrical battery with 0.50 M (DBPPy)Cl4 shows negligible decay during the 13-day cycling test. As demonstration, the flow battery utilizing 1.0 M (DBPPy)Cl4 as the negolyte and 1-(1-oxyl-2,2′,6,6′-tetramethylpiperidin-4-yl)-1′-(3-(trimethylammonio)propyl)-4,4′-bipyridinium trichloride as the posolyte exhibits a high capacity retention rate of 99.99% per cycle at 60 mA cm−2.

Electrochemiluminescence enhanced by molecular engineering linear π-conjugated polymer: An ingenious ECL emitter for the construction of exosome sensing platform

Linear π-conjugated polymers (LCPs) with π-electron conjugation system have many remarkable optical characteristics such as fluorescence and electrochemiluminescence (ECL). However, the extremely strong interchain interaction and π-π stacking limit the luminescence efficiency. In this work, 1H-1,2,4-triazole-3,5-diamine was chosen as the polymer monomer and reacted with terephthalaldehyde via simple Schiff base condensation to synthesize LCPs. Subsequently, molecular engineering strategy was adopted to construct zirconium-based LCPs (MLCPs), which not only prevented π-π stacking but also ensured that extended π-coupling was maintained in the LCPs, thus effectively promoting charge transport and achieving strong luminescence. Second, the coreactant polyethyleneimine (PEI) was assembled onto the MLCPs (MLCPs@PEI) to further promote the emission of ECL. To further explore the potential of the obtained MLCPs@PEI as emerging ECL emitter, colorectal cancer exosome was chosen as model biomarker, and an innovative ECL ratiometric system based on MLCPs@PEI and luminol was designed to improve the validity and accuracy of the sensors. This research provides a fresh nanoplatform for exosome detection and broadens the application of LCPs in ECL immunoassay.

Molecular Engineering for Modulating Photocatalytic Hydrogen Evolution of Fully Conjugated 3D Covalent Organic Frameworks

AbstractCovalent organic frameworks (COFs) have recently shown great potential for photocatalytic hydrogen production. Currently almost all reports are focused on two‐dimensional (2D) COFs, while the 3D counterparts are rarely explored due to their non‐conjugated frameworks derived from the sp3 carbon based tetrahedral building blocks. Here, we rationally designed and synthesized a series of fully conjugated 3D COFs by using the saddle‐shaped cyclooctatetrathiophene derivative as the building block. Through molecular engineering strategies, we thoroughly discussed the influences of key factors including the donor‐acceptor structure, hydrophilicity, specific surface areas, as well as the conjugated/non‐conjugated structures on their photocatalytic hydrogen evolution properties. The as‐synthesized fully conjugated 3D COFs could generate the hydrogen up to 40.36 mmol h−1 g−1. This is the first report on intrinsic metal‐free 3D COFs in photocatalytic hydrogen evolution application. Our work provides insight on the structure design of 3D COFs for highly‐efficient photocatalysis, and also reveals that the semiconducting fully conjugated 3D COFs could be a useful platform in clear energy‐related fields.

Molecular Engineering for Modulating Photocatalytic Hydrogen Evolution of Fully Conjugated 3D Covalent Organic Frameworks.

Covalent organic frameworks (COFs) have recently shown great potential for photocatalytic hydrogen production. Currently almost all reports are focused on two-dimensional (2D) COFs, while the 3D counterparts are rarely explored due to their non-conjugated frameworks derived from the sp3 carbon based tetrahedral building blocks. Here, we rationally designed and synthesized a series of fully conjugated 3D COFs by using the saddle-shaped cyclooctatetrathiophene derivative as the building block. Through molecular engineering strategies, we thoroughly discussed the influences of key factors including the donor-acceptor structure, hydrophilicity, specific surface areas, as well as the conjugated/non-conjugated structures on their photocatalytic hydrogen evolution properties. The as-synthesized fully conjugated 3D COFs could generate the hydrogen up to 40.36 mmol h-1 g-1. This is the first report on intrinsic metal-free 3D COFs in photocatalytic hydrogen evolution application. Our work provides insight on the structure design of 3D COFs for highly-efficient photocatalysis, and also reveals that the semiconducting fully conjugated 3D COFs could be a useful platform in clear energy-related fields.

Indigo as a Low‐Cost Redox‐Active Sorbent for Electrochemically Mediated Carbon Capture

AbstractClimate change has driven the need for carbon capture to mitigate anthropogenic greenhouse gas emissions, yet current thermochemical methods are hampered by high energy intensities. Electrochemically mediated carbon capture (EMCC) utilizing redox‐active carbon dioxide (CO2) carriers is an attractive alternative for carbon capture. Here, an economical vat dye compound, indigo, is presented, which can reversibly capture and release CO2 upon electrochemical reduction and oxidation, respectively. Electrode and electrolyte engineering strategies are utilized to improve the reversibility and stability of indigo for EMCC. A bench‐scale prototypical fixed‐bed carbon capture device is constructed to demonstrate indigo's EMCC performance under various practically relevant conditions, such as simulated flue gas and extremely dilute sources pertinent to direct air capture. A hybrid sorbent electrode‐gas diffusion layer approach is revealed to alleviate CO2 mass transport limitations, achieving ≈80% CO2 capacity utilization under a 15% CO2 feed stream. Furthermore, a reactive‐diffusive mass transport model is developed to illustrate engineering approaches that can be universally applied to optimize fixed‐bed EMCC systems. This work advances the potential for a class of low‐cost sorbents for EMCC while underscoring the importance of molecular, electrolyte, materials, and device engineering strategies to enable high‐performance carbon capture.

Aptameric hirudins as selective and reversible EXosite-ACTive site (EXACT) inhibitors

Potent and selective inhibition of the structurally homologous proteases of coagulation poses challenges for drug development. Hematophagous organisms frequently accomplish this by fashioning peptide inhibitors combining exosite and active site binding motifs. Inspired by this biological strategy, we create several EXACT inhibitors targeting thrombin and factor Xa de novo by linking EXosite-binding aptamers with small molecule ACTive site inhibitors. The aptamer component within the EXACT inhibitor (1) synergizes with and enhances the potency of small-molecule active site inhibitors by many hundred-fold (2) can redirect an active site inhibitor’s selectivity towards a different protease, and (3) enable efficient reversal of inhibition by an antidote that disrupts bivalent binding. One EXACT inhibitor, HD22-7A-DAB, demonstrates extraordinary anticoagulation activity, exhibiting great potential as a potent, rapid onset anticoagulant to support cardiovascular surgeries. Using this generalizable molecular engineering strategy, selective, potent, and rapidly reversible EXACT inhibitors can be created against many enzymes through simple oligonucleotide conjugation for numerous research and therapeutic applications.

Sterically Twisted Mitochondria‐Targeting Photosensitizers for Augmented Near‐Infrared II Fluorescence‐Guided Photodynamic Immunotherapy

AbstractNear‐infrared (NIR) fluorescent mitochondria‐targeting photosensitizers (PSs) hold great potential for efficient image‐guided cancer phototherapy, but it remains challenging to develop PSs concurrently integrating high‐contrast NIR‐II fluorescence imaging and efficient therapeutic capabilities. Herein, a heptamethine cyanine (HCy) PS (termed I2HCy‐TPE nanoparticles (NPs)) by a molecular engineering strategy combining the heavy atom effect and structural distortion is reported. The heavy atom iodine is introduced to boost the intersystem crossing process, and the bulky tetraphenylethylene (TPE) moiety placed at the meso‐position of the heptamethine chain creates a highly distorted conformation in I2HCy‐TPE, theoretically verified by density functional theory calculations. This strategy synergistically promotes the 1O2 generation efficiency and assure the strong NIR fluorescence emission in aggregated states. Combining with the intrinsic mitochondria‐targeting capability, I2HCy‐TPE NPs are able to cause mitochondria‐targeted damage of cancer cells via the PDT and immunogenetic cell death‐triggered immune responses under NIR laser irradiation. In vivo experiments demonstrate that the biocompatible I2HCy‐TPE NPs present exceptional capability for in vivo NIR‐II fluorescence bioimaging of whole‐body and blood vessels, and exert efficient NIR‐II fluorescence‐guided photodynamic immunotherapy against triple‐negative breast cancer.

Driving Triplet State Population in Benzothioxanthene Imide Dyes: Let's twist!

Controlling the formation of photoexcited triplet states is critical for many (photo)chemical and physical applications. Here, we demonstrate that a permanent out-of-plane distortion of the benzothioxanthene imide (BTI) dye promotes intersystem crossing by increasing spin-orbit coupling. This manipulation was achieved through a subtle chemical modification, specifically the bay-area methylation. Consequently, this simple yet efficient approach expands the catalog of known molecular engineering strategies for synthesizing heavy atom-free, dual redox-active, yet still emissive and synthetically accessible photosensitizers.

Molecular Engineering to Regulate the Pseudo-Graphitic Structure of Hard Carbon for Superior Sodium Energy Storage.

Resin-derived hard carbons have shown great advantages in serving as promising anode materials for sodium-ion batteries due to their flexible microstructure tunability. However, it remains a daunting challenge to rationally regulate the pseudo-graphitic crystallite and defect of hard carbon toward advanced sodium storage performance. Herein, a molecular engineering strategy is demonstrated to modulate the cross-linking degree of phenolic resin and thus optimize the microstructure of hard carbon. Remarkably, the resorcinol endows resin with a moderate cross-linking degree, which can finely tune the pseudo-graphitic structure with enlarged interlayer spacing and restricted surface defects. As a consequence, the optimal hard carbon delivers a notable reversible capacity of 334.3mAhg-1 at 0.02Ag-1, a high initial Coulombic efficiency of 82.1%, superior rate performance of 103.7mAhg-1 at 2Ag-1, and excellent cycling durability over 5000 cycles. Furthermore, kinetic analysis and in situ Raman spectroscopy are performed to reveal the electrochemical advantage and sodium storage mechanism. This study fundamentally sheds light on the molecular design of resin-based hard carbons to advance sodium energy for scale-up applications.

Research Progress of β-Ketoenamine-Linked Covalent Organic Frameworks for Photocatalytic Hydrogen Evolution

β-Ketoamide covalent organic frameworks (COFs), also named Tp-COFs, are considered to be a milestone material in the history of photocatalysts because of their excellent visible-light absorption, high crystallinity, ultra-high stability and structural diversity. In recent years, a large number of Tp-COFs and their composites have been successfully constructed based on molecular or composite engineering strategies, and exhibited splendid photocatalytic water splitting activity. In comparison with a composite strategy, the molecular engineering technique effectively avoids interface problems by designing and preparing frameworks at the molecular level. Therefore, it is necessary to timely summarize the construction of Tp-COF photocatalysts based on the molecular engineering strategy, so as to provide some theoretical basis and enlightenment for the subsequent development of high-performance Tp-COFs. Finally, the shortcomings and challenges of this technique and personal views on the further development of Tp-COFs are presented.

Molecular Engineering of D‐π‐A Conjugate with N‐Heterocycle Purine for Enhanced ROS Generation and Photodynamic Therapy

AbstractThe efficient generation of reactive oxygen species (ROS) is crucial for the photodynamic therapy (PDT) effect. The D‐π‐A molecular engineering strategy can effectively separate the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) distribution to achieve a smaller energy gap thereby facilitating ROS generation of photosensitizers (PSs). Incorporating heterocycles as π‐bridges can not only extend the conjugation system with improving the degree of π‐delocalization but also effectively accelerate the intersystem crossing process. Herein, a N‐heterocycle purine is innovatively integrated into the D‐π‐A structure as a π‐bridge, which significantly enhances the photodynamic performance by achieving high levels of Type I and Type II ROS generation. The most potent TPM‐QN2 is obtained by modulating the electron‐withdrawing ability of the acceptor (quinolinium), with a 1O2 yield of 9.32, which is the highest yield reported to date. Furthermore, these purine‐based PSs exhibit excellent capabilities in promoting cell photodynamic ablation and inhibiting tumor tissue growth. This novel approach of introducing natural heterocycles provides a promising avenue for developing high‐performance PSs and promoting tumor phototherapy.

Near-Infrared Light-Driving Organic Photothermal Agents with an 88.9% Photothermal Conversion Efficiency for Image-Guided Synergistic Phototherapy.

Photothermal agents (PTAs) with desirable near-infrared (NIR) absorption and excellent photothermal conversion efficiency (PCE) are ideal candidates for cancer treatment. However, numerous PTAs still require high-intensity and long-duration laser irradiation to completely ablate the tumor during the photothermal therapy (PTT) process, resulting in light damage to healthy skin and tissue as well as limiting their biomedical applications. Integrating intense NIR absorption and high PCE into a single small-molecule PTA is an important prerequisite for realizing efficient PTT, but is a serious challenge. Herein, a series of donor-acceptor type PTAs (CC1 to NC4) are designed through a molecular engineering strategy. Theoretical calculations and experimental results show that the NIR absorption and photothermal effect from CC1 to NC4 are significantly enhanced as expected. Notably, NC4 nanoparticles exhibit intense NIR absorption, superhigh PCE of up to 88.9% for PTT, photoacoustic imaging and photothermal imaging, and effective reactive oxygen species generation for photodynamic therapy (PDT). The superior PTT/PDT synergistic phototherapeutic efficacy is well demonstrated by the complete elimination of tumor in vivo upon one-time, low-intensity, and short-duration laser irradiation (808nm, 330mW cm-2, and 3min). This work provides a valuable guideline for rational design of PTAs for cancer phototherapy.

Acceptor-donor-acceptor type organic photothermal agents with enhanced NIR absorption and photothermal conversion effect for cancer photothermal therapy

Numerous photothermal agents (PTAs) require high-intensity and long-duration laser excitation for photothermal therapy (PTT), resulting in light damage to healthy skin and tissue as well as limiting their biomedical applications. Integrating desirable near-infrared (NIR) absorption and high photothermal conversion efficiency (PCE) into a single small-molecule PTA is an important prerequisite for realizing efficient PTT, but is a serious challenge. Herein, through molecular engineering strategy, an acceptor-donor-acceptor (A-D-A) type PTA (ADA3) was readily developed for 808 nm laser-driving photothermal imaging and PTT of tumor. Theoretical calculations and experiment results show molecular engineering strategy is significant in regulating the structure and energy gap of PTAs, so as to effectively induce a narrow band gap for NIR absorption and further optimize photothermal properties. ADA3 possesses molar extinction coefficient of 3.1 × 104 M−1 cm−1 at 808 nm, followed being assembled into nanoparticles, ADA3-NPs show high PCE of 80.3%. In vivo experiments indicate that ADA3-NPs have excellent antitumor capability under one-time, low-intensity and short-duration (808 nm, 330 mW/cm2, 3 min) laser irradiation. Therefore, this work definitely exemplifies the enormous potential of molecular engineering strategy and provides an effective method for developing small-molecule PTAs.

Improvement in Dibenzofuran-Based Hole Transport Materials for Flexible Perovskite Solar Cells.

The π-conjugated system and the steric configuration of hole transport materials (HTMs) could greatly affect their various properties and the corresponding perovskite solar cells' efficiencies. Here, a molecular engineering strategy of incorporating different amounts of p-methoxyaniline-substituted dibenzofurans as π bridge into HTMs was proposed to develop oligomer HTMs, named mDBF, bDBF, and tDBF. Upon extending the π-conjugation of HTMs, their HOMO energy levels were slightly deepened, significantly increasing the thermal stability and hole mobility. The incorporation of p-methoxyaniline bridges built one or two additional triphenylamine propeller structures, resulting in a denser film. Here, the tDBF-based n-i-p flexible perovskite solar cells createdchampion efficiency, giving a power conversion efficiency of 19.46%. And the simple synthesis and purification process of tDBF contributed to its low manufacturing cost in the laboratory. This work provided a reference for the development of low-cost and efficient HTMs.

Quantifying Protein Shape to Elucidate Its Influence on Solution Viscosity in High-Concentration Electrolyte Solutions.

Therapeutic proteins with a high concentration and low viscosity are highly desirable for subcutaneous and certain local injections. The shape of a protein is known to influence solution viscosity; however, the precise quantification of protein shape and its relative impact compared to other factors like charge-charge interactions remains unclear. In this study, we utilized seven model proteins of varying shapes and experimentally determined their shape factors (v) based on Einstein's viscosity theory, which correlate strongly with the ratios of the proteins' surface area to the 2/3 power of their respective volumes, based on protein crystal structures resolved experimentally or predicted by AlphaFold. This finding confirms the feasibility of computationally estimating protein shape factors from amino acid sequences alone. Furthermore, our results demonstrated that, in high-concentration electrolyte solutions, a more spherical protein shape increases the protein's critical concentration (C*), the transition concentration beyond which protein viscosity increases exponentially relative to concentration increases. In summary, our work elucidates protein shape as a key determinant of solution viscosity through quantitative analysis and comparison with other contributing factors. This provides insights into molecular engineering strategies to optimize the molecular design of therapeutic proteins, thus optimizing their viscosity.