Guidelines For Molecular Design Research Articles

White-light activatable organic NIR-II luminescence nanomaterials for imaging-guided surgery

While second near-infrared (NIR-II) fluorescence imaging is a promising tool for real-time surveillance of surgical operations, the previously reported organic NIR-II luminescent materials for in vivo imaging are predominantly activated by expensive lasers or X-ray with high power and poor illumination homogeneity, which significantly limits their clinical applications. Here we report a white-light activatable NIR-II organic imaging agent by taking advantages of the strong intramolecular/intermolecular D-A interactions of conjugated Y6CT molecules in nanoparticles (Y6CT-NPs), with the brightness of as high as 13315.1, which is over two times that of the brightest laser-activated NIR-II organic contrast agents reported thus far. Upon white-light activation, Y6CT-NPs can achieve not only in vivo imaging of hepatic ischemia reperfusion, but also real-time monitoring of kidney transplantation surgery. During the surgery, identification of the renal vasculature, post-reconstruction assessment of renal allograft vascular integrity, and blood supply analysis of the ureter can be vividly depicted by using Y6CT-NPs with high signal-to-noise ratios upon clinical laparoscopic LED white-light activation. Our work provides efficient molecular design guidelines towards white-light activatable imaging agent and highlights an opportunity for precision imaging theranostics.

Spotlight on Zinc: Exploring the Visible Light Responsiveness of Zinc Complexes.

Group 12 element zinc(II)-based d10 complexes have long been known for their inherent colorlessness, which has limited their applications in visible light-driven photophysical and photochemical applications, despite the attractiveness of inexpensive and low-toxicity zinc metal. Based on precedents with nickel(0) and copper(I) complexes, which also adopt the d10 electronic configuration, achieving a visible light response from zinc(II) complexes seems feasible; however, investigations and proactive design strategies specifically tailored to zinc remain lacking. In this context, the present invited concept paper highlights zinc's potential for visible light responsiveness and evaluates how molecular designs can achieve this capability. After delineating the differences between zinc and other d10 metal centers, we review recent developments in zinc complexes that exhibit visible light absorption and compare these complexes with previously reported colorless complexes to identify key distinctions. This study provides critical insights into the molecular design guidelines that are pivotal for harnessing the emerging potential of zinc for visible light responses.

Drastically Accelerated Radical Recombination Kinetics of a Hexaarylbiimidazole Derivative.

More than 60 years have passed since the discovery of hexaarylbiimidazole (HABI), which exhibits a characteristic photochromism that produces colored lophyl radicals through a radical dissociation reaction induced by light irradiation and reverts to its original state through a radical recombination reaction in the dark. Lophyl radicals are relatively stable among organic radicals, have low reactivity with oxygen, and have a very slow radical recombination reaction rate. HABI has been used industrially as a photoinitiator to date. However, the guidelines for molecular design to accelerate the thermal reverse reaction of HABI are still unknown and remain a challenge. We found that suppressing the rotation of the phenyl groups attached to the 4- and 5-positions of the imidazole ring of HABI is effective in accelerating the radical recombination reaction. The simple molecular design strategy to accelerate the thermal reverse reaction of HABI is expected to improve the performance of photoinitiators and photoresponsive materials that utilize HABI as a photoresponsive unit.

Dinuclear Cu(I) molecular electrocatalyst for CO2-to-C3 product conversion

Molecular metal complex catalysts are highly tunable in terms of their CO2 reduction performance by means of their flexible molecular design. However, metal complex catalysts have challenges in their structural stability and it has not been possible to synthesize high-value-added C3 products due to their inability to perform C–C coupling. Here we show a CO2 reduction reaction catalysed by a Br-bridged dinuclear Cu(I) complex that produces C3H7OH with high robustness during the reaction. The C–C coupling reaction mechanism was analysed by experimental operando surface-enhanced Raman scattering analysis, and theoretical quantum-chemical calculations proposed the formation of a C–C coupling intermediate species with substrate incorporation between the two Cu centres. Molecular design guidelines based on this discovery offer an approach to developing next-generation catalysts that generate multicarbon CO2 reduction products.

What is the Limit Size of 2D Conjugated Extension on Central Units of Small Molecular Acceptors in Organic Solar Cells?

2D conjugated extension on central units of small molecular acceptors (SMAs) has gained great successes in reaching the state-of-the-art organic photovoltaics. Whereas the limit size of 2D central planes and their dominant role in constructing 3D intermolecular packing networks are still elusive. Thus, by exploring a series of SMAs with gradually enlarged central planes, it is demonstrated that, at both single molecular and aggerated levels, there is an unexpected blue-shift for their film absorption but preferable reorganization energies, exciton lifetimes and binding energies with central planes enlarging, especially when comparing to their Y6 counterpart. More importantly, the significance of well-balanced molecular packing modes involving both central and end units is first disclosed through a systematic single crystal analysis, indicating that when the ratio of central planes area/end terminals area is no more than 3 likely provides a preferred 3D intermolecular packing network of SMAs. By exploring the limit size of 2D central planes, This work indicates that the structural profiles of ideal SMAs may require suitable central unit size together with proper heteroatom replacement instead of directly overextending 2D central planes to the maximum. These results will likely provide some guidelines for future better molecular design.

Polarity and orbital driven reduction in contact resistance in organic devices with functionalized electrodes.

Interlayers at electrode interfaces have been shown to reduce contact resistance in organic devices. However, there still needs to be more clarity regarding the role of microscopic properties of interlayer functionalized interfaces on device behavior. Here, we show that the impact of functionalized electrodes on device characteristics can be predicted by a few critical computationally derived parameters representing the interface charge distribution and orbital interactions. The significant influences of interfacial orbital interactions and charge distribution over device and interface properties are exhibited. Accordingly, a function is developed based on these parameters that capture their effect on the interface resistance. A strong correlation is observed, such that enhanced orbital interactions and reduced charge separation at the interface correspond to low resistance regardless of the individual molecules utilized as the interlayer. The charge distribution and orbital interactions vary with the molecular structure of the interlayer, allowing the tuning of device characteristics. Hence, the proposed function serves as a guideline for molecular design and selection for interlayers in organic devices.

Mitochondrial sensitive probe with aggregation‐induced emission characteristics for early brain diagnosis of Parkinson's disease

AbstractThe early diagnosis of Parkinson's disease (PD) provides opportunities for early intervention to slow the progression of neurological degeneration in patients, particularly as the aging population increases in our society. Among a series of pathological features of PD, mitochondria abnormalities have been identified as central event that occurs at the early stage of PD. However, the method for detecting mitochondrial abnormalities‐associated early PD has not been fully developed. We herein report a specifically mitochondrial targeting probe (named TPA‐BT‐SCP) that is able to characterize mitochondria abnormalities for early diagnosis of PD and monitor PD neurodegenerative progress. The probe is an aggregation‐induced emission (AIE) probe with a strong positive charge, a 3D distorted molecular structure, and a separated HOMO‐LUMO distribution, designed with unique molecular design guidelines. Our research demonstrated that TPA‐BT‐SCP could emit stable and strong fluorescence, and rapidly accumulate in mitochondria due to the negative charge. After intranasal administration of 1‐methy‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced PD mice, TPA‐BT‐SCP successfully bypassed the blood−brain barrier to light up the brain, allowing the grading of PD severity based on its high sensitivity. Taken together, this work develops a novel AIE probe that exhibits dramatically high sensitivity to mitochondrial changes and enables noninvasive diagnosis of early PD in the brain.

Inside Cover Picture

This cover picture shows a new A‐DA’D‐A type pentacyclic small molecule acceptor BZ4F‐OEH based on a “heteroatom side‐chains” modification strategy, which introduced oxygen atom at the third‐position of the side chain on the thiophene unit, and the BZ4F‐OEH‐based binary device achieved a high power conversion efficiency of 16.56%, which is among the highest values for the pentacyclic small molecule acceptors. This work provides an important guideline for future molecular design. More details are discussed in the article by Yuan et al. on page 1815—1822.image

Enhancing Carrier Transport via σ-Linkage Length Modulation in D-σ-A Semiconductors for Photocatalytic Oxidation.

Carrier transport is an equally decisive factor as carrier separation for elevating photocatalytic efficiency. However, limited by indefinite structures and low crystallinities, studies on enhancing carrier transport of organic photocatalysts are still in their infancy. Here, we develop an σ-linkage length modulation strategy to enhance carrier transport in imidazole-alkyl-perylene diimide (IMZ-alkyl-PDI, corresponding to D-σ-A) photocatalysts by controlling π-π stacking distance. Ethyl-linkage can shorten π-π stacking distance (3.19 Å) the most among IMZ-alkyl-PDIs (where alkyl=none, ethyl, and n-propyl) via minimizing steric hindrance between D and A moieties, which leads to the fastest carrier transport rates. Thereby, IMZ-ethyl-PDI exhibits remarkable enhancement in phenol degradation with 32-fold higher rates than IMZ-PDI, as well as the oxygen evolution rate (271-fold increased). In microchannel reactors, IMZ-ethyl-PDI also presents 81.5 % phenol removal with high-flux surface hydraulic loading (44.73 L m-2 h-1 ). Our findings provide a promising molecular design guideline for high-performance photocatalysts and elucidate crucial internal carrier transport mechanisms.

Enhancing Carrier Transport via σ‐Linkage Length Modulation in D‐σ‐A Semiconductors for Photocatalytic Oxidation

AbstractCarrier transport is an equally decisive factor as carrier separation for elevating photocatalytic efficiency. However, limited by indefinite structures and low crystallinities, studies on enhancing carrier transport of organic photocatalysts are still in their infancy. Here, we develop an σ‐linkage length modulation strategy to enhance carrier transport in imidazole‐alkyl‐perylene diimide (IMZ‐alkyl‐PDI, corresponding to D‐σ‐A) photocatalysts by controlling π–π stacking distance. Ethyl‐linkage can shorten π–π stacking distance (3.19 Å) the most among IMZ‐alkyl‐PDIs (where alkyl=none, ethyl, and n‐propyl) via minimizing steric hindrance between D and A moieties, which leads to the fastest carrier transport rates. Thereby, IMZ‐ethyl‐PDI exhibits remarkable enhancement in phenol degradation with 32‐fold higher rates than IMZ‐PDI, as well as the oxygen evolution rate (271‐fold increased). In microchannel reactors, IMZ‐ethyl‐PDI also presents 81.5 % phenol removal with high‐flux surface hydraulic loading (44.73 L m−2 h−1). Our findings provide a promising molecular design guideline for high‐performance photocatalysts and elucidate crucial internal carrier transport mechanisms.

A‐DA’D‐A Type Pentacyclic Small Molecule Acceptors to Exceed 16.5% Efficiency by Heteroatom Effect at the Outer Side Chain

Comprehensive SummaryIn this work, we adopt a “heteroatom side‐chains” modification strategy to modify the thiophene units in A‐DA'D‐A (acceptor‐donor‐acceptor’‐donor‐acceptor) type pentacyclic SMAs (small molecule acceptors), that is, introducing branched alkyl chain at the β‐position of thiophene instead of straight alkyl chain, and then introducing oxygen atom at the third‐position on the basis of branched chain. Two new pentacyclic SMAs (BZ4F‐EH and BZ4F‐OEH) were synthesized, and the influence of the heteroatom side‐chains on photoelectric properties of A‐DA'D‐A type pentacyclic SMAs was systematically studied. Compared with our previously reported BZ4F (Y26), BZ4F‐EH shows slightly blue‐shifted absorption, while BZ4F‐OEH has obvious red‐shifted absorption. As a result, BZ4F‐OEH‐based binary device achieved a high power conversion efficiency (PCE) of 16.56% with a fill factor (FF) of 79.3%, which is the highest efficiency of pentacyclic SMAs to date. The results indicated that the modification of hetero‐atomization on the β‐position of thiophene is a simple and efficient way to improve the PCE of A‐DA'D‐A type SMAs, and this work provides an important guideline for future molecular design.

Amidoamine Oxide Surfactants as Low-Molecular-Weight Hydrogelators: Effect of Methylene Chain Length on Aggregate Structure and Rheological Behavior.

Rheology control is an important issue in many industrial products such as cosmetics and paints. Recently, low-molecular-weight compounds have attracted considerable attention as thickeners/gelators for various solvents; however, there is still a significant need for molecular design guidelines for industrial applications. Amidoamine oxides (AAOs), which are long-chain alkylamine oxides with three amide groups, are surfactants that act as hydrogelators. Here, we show the relationship between the length of methylene chains at four different locations of AAOs, the aggregate structure, the gelation temperature Tgel, and the viscoelasticity of the formed hydrogels. As seen from the results of electron microscopic observations, the aggregate structure (ribbon-like or rod-like) can be controlled by changing the length of methylene chain in the hydrophobic part, the length of methylene chain between the amide and amine oxide groups, and the lengths of methylene chains between amide groups. Furthermore, hydrogels consisting of rod-like aggregates showed significantly higher viscoelasticity than those consisting of ribbon-like aggregates. In other words, it was shown that the gel viscoelasticity could be controlled by changing the methylene chain lengths at four different locations of the AAO.

4'-OH as the Action Site of Lipids and MRP1 for Enhanced Transdermal Delivery of Flavonoids.

To date, the transdermal delivery study mainly focused on the drug delivery systems' design and efficacy evaluation. Few studies reported the structure-affinity relationship of the drug with the skin, further revealing the action sites of the drugs for enhanced permeation. Flavonoids attained a considerable interest in transdermal administration. The aim is to develop a systematic approach to evaluate the substructures that were favorable for flavonoid delivery into the skin and understand how these action sites interacted with lipids and bound to multidrug resistance protein 1 (MRP1) for enhanced transdermal delivery. First, we investigated the permeation properties of various flavonoids on the porcine skin or rat skin. We found that 4'-OH (hydroxyl group on the carbon 4' position) rather than 7-OH on the flavonoids was the key group for flavonoid permeation and retention, while 4'-OCH3 and -CH2═CH2-CH-(CH3)2 were unfavorable for drug delivery. 4'-OH could decrease flavonoids' lipophilicity to an appropriate log P and polarizability for better transdermal drug delivery. In the stratum corneum, flavonoids used 4'-OH as a hand to specifically grab the C═O group of the ceramide NS (Cer), which increased the miscibility of flavonoids and Cer and then disturbed the lipid arrangement of Cer, thereby facilitating their penetration. Subsequently, we constructed overexpressed MRP1 HaCaT/MRP1 cells by permanent transfection of human MRP1 cDNA in wild HaCaT cells. In the dermis, we observed that 4'-OH, 7-OH, and 6-OCH3 substructures were involved in H-bond formation within MRP1, which increased the flavonoid affinity with MRP1 and flavonoid efflux transport. Moreover, the expression of MRP1 was significantly enhanced after the treatment of flavonoids on the rat skin. Collectively, 4'-OH served as the action site for increased lipid disruption and enhanced affinity for MRP1, which facilitate the transdermal delivery of flavonoids, providing valuable guidelines for molecular modification and drug design of flavonoids.

Recent progress and prospects of fluorescent materials based on narrow emission

MR-TADF emitters with narrow emission have been developed and are expected to become fourth-generation emitters for HD-OLEDs, with molecular design guidelines and commercial prospects outlined in this review.

Design of polyimides with targeted glass transition temperature using a graph neural network

Models were obtained to predict the Tg of polyimides and compared with the experimental results. 110 polyimides are screened through high-throughput calculations and chemical knowledge. Novel molecular design guidelines are provided.

Incorporation of Robust NIR-II Fluorescence Brightness and Photothermal Performance in a Single Large π-Conjugated Molecule for Phototheranostics.

Second near-infrared (NIR-II, 1000-1700nm) window fluorescence imaging-guided photothermal therapy probes are promising for precise cancer phototheranostics. However, most of the currently reported probes do not demonstrate high NIR-II fluorescent brightness (molar absorption coefficient (ε) × quantum yield (QY)) and photothermal performance (ε × photothermal conversion efficiency (PCE)) in a single molecule. Herein, a versatile strategy to solve this challenge is reported by fabricating a large π-conjugated molecule (BNDI-Me) with a rigid molecular skeleton and flexible side groups. The proposed BNDI-Me nanoprobe boosts the ε and simultaneously optimizes its QY and PCE. Therefore, high NIR-II fluorescent brightness (ε × QY = 2296 m-1 cm-1 ) and strong photothermal performance (ε × PCE = 82000) are successfully incorporated in a single small molecule, and, to the best of knowledge, either of these two parameters is better than the best currently available fluorescent or photothermal probes. Thus, superior NIR-II imaging effect in vivo and high photothermal tumor inhibition rate (81.2%) at low systemic injection doses are obtained. The work provides further insights into the relationship of photophysical mechanisms and structures, and presents promising molecular design guidelines for the integration of more efficient multiple theranostic functions in a single molecule.

Synchronous Doping Effects of Cathode Interlayers on Efficient Organic Solar Cells

An in-depth understanding of the role of cathode interlayers in nonfullerene organic solar cells (OSCs) is challenging due to ambiguous and complicated interfacial doping, which complicates molecular designs and hinders progress in optoelectronic performance. Herein, we describe synchronous doping effects (a combination of the cathode interlayer’s self-doping and its doping on acceptors in the active layer) of cathode interlayers. The electronic nature of π-conjugated cores in cathode interlayer materials has a negligible influence on nonfullerene acceptor doping but an obvious influence on their self-doping. A synchronous doping effect generated by the amine-substituted fullerene (C60-N), with its electron-withdrawing C60 core, facilitates interfacial charge transport and collection, affording a remarkable power conversion efficiency > 18% for PM6:L8-BO based OSCs, which is among the highest reported values for binary OSCs. This discovery of synchronous doping on interfacial modification provides new and useful molecular design guidelines for high-performance cathode modifiers in organic electronics.

Temperature-Dependent Dual Fluorescence from Small Organic Molecules

The temperature-dependent dual fluorescence from a single component of small organic molecules (SOMs) is very promising for the ratiometric fluorescence sensing of temperature. However, the SOM-based fluorophores typically only show one fluorescence band. It is thus very challenging to achieve dual fluorescence, let alone the dual fluorescence that is sensitive to temperature. Herein, in this short review, we briefly summarized the examples of SOM-based fluorophores exhibiting temperature-dependent dual fluorescence. Through representative examples, we mainly focus on the illustration of the intrinsic mechanisms of this unusual phenomenon, which may take place because of the presence of two local minimum conformations that are thermally equilibrated in the ground state, the presence of two local minimum conformations in the first excited state as the result of significant structural relaxation upon excitation, or the presence of thermal equilibrium between the first and second excited states. Hopefully, the discussions in this short review will provide some important guidelines for the further rational molecular design of such fluorophores.

Configurable Organic Charge Carriers toward Stable Perovskite Photovoltaics.

Due to their solution processability and unique photoelectric characteristics, perovskite solar cells (PSCs) have shown considerable promise in the area of renewable energy. Although their power conversion efficiency (PCE) has risen from 3.8% to 25.7% in only a few years, their short lifetime and high material prices continue to be key roadblocks to commercial viability. Charge transporting materials (CTMs), such as hole/electron transporting materials, are critical components in PSCs because they not only govern hole or electron extraction and transporting from the perovskite layer to the electrodes but also protect the perovskite from direct contact with the ambient environment. CTMs are split into two types: inorganic CTMs (ICTMs) and organic CTMs (OCTMs). Because of their inexpensive prices, well-adjusted energy levels, and low temperature solution-processed features, OCTMs have been more frequently explored and employed than ICTMs. Various forms of OCTMs with more straightforward synthetic pathways and better performance have been thoroughly researched. Recent achievements in the development of OCTMs will be discussed and evaluated on a molecular level in this study, which will include a systematic categorization of OCTMs based on molecular functionalization techniques. In order to achieve highly efficient and stable PSCs, we will present insights on the structure-property relationship in the design of OCTMs as well as device stability. We hope that this analysis will serve as a comprehensive reference to molecular design guidelines for various types of OCTMs, spurring greater research toward designing highly efficient and OCTMs for stable PSCs.

Mechanistic Studies for the Rational Design of Multivalent Glycodendrimers.

We have synthesized B-antigen-displaying dendrimers (16-mers) with different sizes and evaluated their affinity to their IgM antibody in order to investigate which design features lead to effective multivalency. Unexpectedly, the smallest dendrimer, which cannot chelate the multiple binding sites of IgM, clearly exhibited multivalency, together with an affinity similar to or higher than those of the larger dendrimers. These results indicate that the statistical rebinding model, which involves the rapid exchange of clustered glycans, significantly contributes to the multivalency of glycodendrimers. Namely, in the design of glycodendrimers, high-density glycan presentation to enhance statistical rebinding should be considered in addition to the ability to chelate multiple binding sites. This notion stands in contrast to the currently prevailing scientific consensus, which prioritizes the chelation model. This study thus provides new and important guidelines for molecular design of glycodendrimers.