ACKNOWLEDGEMENTS

24 Apr 2025

Submitted by (Bold are A*STAR Staff): Krishna M. Gupta, Srinivasulu Aitipamula, Xavier Chin, Pui Shan Chow

Research Institute: ISCE2

Title of Paper: Synergistic Computational and Experimental Investigation of Covalent Organic Frameworks for Efficient Alcohol Dehydration

Publish in: Applied Materials & Interfaces

Abstract: Covalent organic frameworks (COFs), a promising class of nanoporous materials, have received significant attention for membrane separation. Currently, several COFs are reported for alcohol dehydration, but they are not efficient owing to the pervasive challenge to separate small-sized molecular mixture. Herein, first we have computationally explored a series of COFs with different functionality and aperture size as pervaporation (PV) membrane and identified a novel COF for efficient dehydration of water/alcohol mixtures (90 wt % IPA, 90 wt % n-butanol and 90 wt % t-butanol). Subsequently, the best-performing COF was experimentally synthesized and characterized, and its sorption properties were correlated with computational results. Molecular dynamics (MD) simulations revealed that solvent permeation fluxes are predominantly influenced by the pore aperture of COFs, and larger pore aperture exhibits higher flux. Conversely, the separation factor is primarily determined by the polarity of the pore functional groups. Among the tested COF membranes, TpPa-1-OC3H6OCH3 demonstrated superior performance, surpassing the current state-of-the-art membranes. The activation energy (Ea) for water permeation in alcohol mixtures through TpPa-1-OC3H6OCH3 is mostly governed by water–alcohol interactions. Furthermore, experimental evaluation of the COFs indicated a plate-like morphology for TpPa-1-OC3H6OCH3 which ascertained a 2D-sheet-like structure. TpPa-1 showed greater sorption than TpPa-1-OC3H6OCH3 with all of the solvents tested owing to the inability of the solvent molecules to enter the relatively small pores in the later COF. This is in accordance with the MD simulation predictions, which indicated that the solvent molecules cannot penetrate the small pores of TpPa-1-OC3H6OCH3. This work synergistically integrates computational and experimental approaches to develop novel COFs with superior performance compared to previously reported PV membranes, paving the way for advanced membranes for sustainable solvent recovery.

URL:  https://doi.org/10.1021/acsami.5c01219

16 Apr 2025

Submitted by (Bold are A*STAR Staff): Jiawei Liu, Yifan Xu, Ruihuan Duan, Mingsheng Zhang, Yue Hu, Mengxin Chen, Bo Han, Jinfeng Dong, Carmen Lee, Loku Singgappulige Rosantha Kumara, Okkyun Seo, Jochi Tseng, Takeshi Watanabe, Zheng Liu, Qiang Zhu, Jianwei Xu, Man-Fai Ng, Dongshuang Wu & Qingyu Yan 

Research Institute: IMRE, ISCE2

Title of Paper: Reaction-driven formation of anisotropic strains in FeTeSe nanosheets boosts low-concentration nitrate reduction to ammonia

Publish in: Nature Communications

Abstract: FeM (M = Se, Te) chalcogenides have been well studied as promising magnets and superconductors, yet their potential as electrocatalysts is often considered limited due to anion dissolution and oxidation during electrochemical reactions. Here, we show that by using two-dimensional (2D) FeTeSe nanosheets, these conventionally perceived limitations can be leveraged to enable the reaction-driven in-situ generation of anisotropic in-plane tensile and out-of-plane compressive strains during the alkaline low-concentration nitrate reduction reaction (NO3−RR). The reconstructed catalyst demonstrates enhanced performance, yielding ammonia with a near-unity Faradaic efficiency and a high yield rate of 42.14 ± 2.06 mg h−1 mgcat−1. A series of operando synchrotron-based X-ray measurements and ex-situ characterizations, alongside theoretical calculations, reveal that strain formation is ascribed to chalcogen vacancies created by partial Se/Te leaching, which facilitate the adsorption and dissociation of OH−/NO3− from the electrolyte, resulting in an O(H)-doped strained lattice. Combined electrochemical and computational investigations suggest that the superior catalytic performance arises from the synergistic contributions from the exposed strained Fe sites and surface hydroxyl groups. These findings highlight the potential of 2D transition metal chalcogenides for in-situ structural engineering during electrochemical reactions to enhance catalytic activity for NO3−RR and beyond.

URL:  https://doi.org/10.1038/s41467-025-58940-x

10 Apr 2025

Submitted by (Bold are A*STAR Staff): Ziyu Mi, Yuke Li, Chao Wu, Mingsheng Zhang, Xun Cao, Shibo Xi, Jia Zhang & Wan Ru Leow

Research Institute: IHPC, IMRE, ISCE2

Title of Paper: CoOx clusters-decorated IrO2 electrocatalyst activates NO3- mediator for benzylic C-H activation

Publish in: Nature Communications

Abstract: Electrochemical conversion of petrochemical-derived hydrocarbons to high-value oxygenates can utilize renewable energy and reduce carbon emissions. However, this involves the challenging activation of inert C(sp3)-H bonds at room temperature. Here, we introduce an electrocatalyst:mediator assembly in which CoOx clusters-decorated IrO2 electrocatalyst activates NO3- mediator to a highly reactive radical capable of abstracting a hydrogen atom from benzylic C-H. The interface between CoOx and IrO2 promotes NO3- activation by facilitating the desorption of NO3● radical for subsequent reaction. Our strategy is demonstrated through the selective oxidation of toluene to benzaldehyde with high Faradaic efficiency of 86( ±1)% at 25 mA/cm2, a factor of >3 times higher than the bare electrocatalyst. The electrocatalyst:mediator assembly is operated stably for 100 h, with minimal decline in performance. When translated into a flow system, a Faradaic efficiency of 60( ±4)% at 200 mA/cm2 was achieved.

URL:  https://doi.org/10.1038/s41467-025-58733-2

31 Mar 2025

Submitted by (Bold are A*STAR Staff): Calvin Pei Yu Wong, Hiroyo Kawai, Zhuojun Jiang, Chengkun Lyu, Cedric Troadec, Kuan Eng Johnson Goh

Research Institute: IHPC, IMRE

Title of Paper: Uncovering Semiconductor Band Structure Effects in Au/n-WS2 Schottky Devices Using Ballistic Electron Emission Microscopy

Publish in: Basic Solid State Physics

Abstract: When fabricating semiconductor devices based on 2D transition metal dichalcogenides (TMD), it is important to understand both the Ohmic and Schottky metal/semiconductor contacts as these contacts directly impact device performance, reproducibility and are important constituents of the interconnects in electronic circuit design. Despite intense ongoing research, a robust understanding of the nature of the metal/TMD contact remains lacking. In this article, the Au/n-WS2 Schottky interface is studied using ballistic electron emission microscopy (BEEM), which is a nanoscale probe of the metal/TMD Schottky interface. The nanoscale Schottky barrier height of the Au/WS2 interface is reported at 0.86 ± 0.03 eV and a second threshold at 1.04 ± 0.06 eV, which corresponds to the secondary conduction band satellite minima in the band structure of WS2 located at 0.20 ± 0.09 eV above the first minimum, in good agreement to theoretically simulated band structures. The results show that BEEM has the energy resolution to uncover contributions from the conduction band satellite minima of WS2 in a device structure, which can be difficult using conventional techniques.

URL:  https://doi.org/10.1002/pssb.202500089

13 Mar 2025

Submitted by (Bold are A*STAR Staff): Yajing Mu, Jinchang Fan, Tianyi Gao, Lina Wang, Lei Zhang, Xiaoxin Zou, Weitao Zheng, Yong-Wei Zhang, Zhi Gen Yu, Xiaoqiang Cui

Research Institute: IHPC

Title of Paper: Tuning Ru–O Coordination for Switching Redox Centers in Acidic Oxygen Evolution Electrocatalysis

Publish in: Angewandte Chemie

Abstract: Avoiding lattice oxygen involvement (oxygen redox) while promoting the coupling of adjacent adsorbed oxygen (metal redox) during the acidic oxygen evolution reaction (OER) is essential for gaining high activity and robust stability in RuO2-based catalysts but remains elusive. Here, we present a precise strategy to selectively activate the metal redox process while suppressing the undesired oxygen redox pathway by fine-tuning the Ru–O coordination number in amorphous RuOx. The optimized catalyst exhibits outstanding acidic OER performance, achieving a low overpotential of 215 mV at 10 mA cm−2 and maintaining stability for 300 h with a negligible degradation rate of 100 µV h−1. X-ray absorption measurements and multiple operando spectra reveal that only Ru2–O11 moieties can selectively activate the metal redox process, whereas Ru2–O9 and Ru2–O8 moieties either trigger both redox pathways or bypass them. Theoretical calculations reveal that Ru2–O11 moiety reduces crystal field splitting energy at active Ru sites, disables lattice oxygen activation, and lowers the energy barrier for oxygen coupling. The strategy developed in this work offers new avenues for switching redox centers and refining OER mechanisms to enhance catalytic performance and long-term stability.

URL:  https://doi.org/10.1002/anie.202504876

04 Mar 2025

Submitted by (Bold are A*STAR Staff): Ziyue Wen, Feng Wu, Man-Fai Ng, Beier Jia, Jinxuan Song, Tianyang Yu, Jinfeng Dong, Anchun Tang, Renjie Chen, Qingyu Yan

Research Institute: IHPC

Title of Paper: Lean-Water Hydrogel with Multipolar Sites for Flexible and High-Performance Aqueous Aluminum Ion Batteries

Publish in: Advanced Materials

Abstract: Rechargeable aqueous aluminum ion batteries (AAIBs) offer a promising avenue for achieving safe, high-energy, and low-cost large-scale energy storage applications. However, the practical development of AAIBs is hindered by competitive reduction reactions in the aqueous solution, which lead to insufficient aluminum (Al) deposition and a severe hydrogen evolution reaction (HRE). In this work, an inorganic/organic hybrid hydrogel with a stable silicon-based network and multiple polar sites is successfully fabricated via an in situ sol-gel polymerization method. The preferential formation of hydrogen bonds between the polar functional groups and water molecules effectively reduces the thermodynamic reactivity of water. Furthermore, X-ray photoelectron spectroscopy (XPS) and time of flight secondary ion mass spectrometry (TOF-SIMS) analyses confirm the formation of a stable, inorganic-rich solid electrolyte interface (SEI) layer, which kinetically suppresses undesirable side reactions. This hydrogel electrolyte exhibits a high ionic conductivity of 2.9 × 10−3 S cm−1 at 25 °C, even under lean-water conditions. As a result, Al|hydrogel|potassium nickel hexacyanoferrate (KNHCF) full cells demonstrate excellent cycling performance, delivering a high initial discharge capacity of 74.9 mAh g−1 at 100 mA g−1 and achieving an outstanding capacity retention of 90.0% after 200 cycles. Additionally, pouch cells exhibit stable open-circuit voltage under various mechanical abuse conditions.

URL:  https://doi.org/10.1002/adma.202500695

25  Feb 2025

Submitted by (Bold are A*STAR Staff): Jian Zhang, Haochun Zhang, Jie Xiong, Shuai Chen, Yong-Wei Zhang, Gang Zhang

Research Institute: IHPC

Title of Paper: Anomalous component-dependent lattice thermal conductivity in MoWTaTiZr refractory high-entropy alloys

Publish in: iScience

Abstract: Refractory high-entropy alloys (RHEAs) have been of great interest due to their excellent mechanical properties at elevated temperatures. However, there are few studies on their thermodynamic properties. Here, we investigate lattice thermal conductivity of MoWTaTiZr RHEAs using the equilibrium molecular dynamics (EMD) method. First, we consider the finite size effect. Then, the effect of temperature on the lattice thermal conductivity is explored. Remarkably, the lattice thermal conductivity and the reciprocal of the temperature are approximately linearly distributed. Finally, by tuning the elemental concentrations in RHEAs, the influence of each composition on the lattice thermal conductivity is studied. Interestingly, the lattice thermal conductivity decreases after increasing the Ti element. Chemical ordering in RHEAs indicates that Ti-Ti pairs tend to form bonds, and increasing Ti concentration is more likely to form Ti-rich clusters. This research is conducive to understanding the thermal behaviors in RHEAs and promoting the applications of RHEAs.

URL:  https://10.1016/j.isci.2025.112100

21 Jan 2025

Submitted by (Bold are A*STAR Staff): Dillon W. P. Tay, Winston Koh, Shi Jun Ang, Zicong Marvin Wong, Yi Wee Lim, Elena Heng, Naythan Z. X. Yeo, Krishnan Adaikkappan, Fong Tian Wong, Yee Hwee Lim

Research Institute: ISCE2, BII, IHPC, IMCB

Title of Paper: A linked Genomics Sequencing and Mass Spectrometry multi-modal dataset and models for Streamlined Natural Products Discovery in Microbial Strain Libraries

Publish in: bioRxiv

Abstract: Natural products (NP) are instrumental in drug development, but their discovery and validation remain challenging and laborious despite advances in both genomic and analytical technologies. In this study, we demonstrate the use of an integrated multi-modal characterization of a microbial strain library for enhanced natural product discovery. This characterization utilizes language- and transformer-based models, integrated through a cross-validate and rank approach to search a mass spectrometry (MS)-genome multi-modal dataset with high confidence. MS data are analysed using an in-house developed tandem mass spectral MS/MS to structural elucidation workflow (WISE) that features a combination of molecular language and transformer-based models to predict corresponding molecular structures. Simultaneously, the related genomic data is pre-processed using the protein language model (ESM2) to extract meaningful embeddings. As a proof of concept, these models and pre-processed linked MS-genome datasets were applied and validated for the rapid identification of microbial strains capable of producing three diverse natural product compounds with precision ranging from 75-100%. Our findings demonstrate the transformative potential of linked MS-genome datasets at the strain-level to accelerate natural product discovery. This approach can expand the range of biotechnological innovations beyond what is currently known and curated, while also greatly reduce the resources and effort needed for discovery.

URL:  https://doi.org/10.1101/2025.01.20.633932

20 Jan 2025

Submitted by (Bold are A*STAR Staff): Hanaé Carrié, Ngak Leng Sim, Pui Mun Wong, Anna Gan, Yi Ting Lau, Polly Poon, Saranya Thangaraju, Iain Tan, Yoon Sim Yap, Kiran Krishnamachari, Limsoon Wong, Anders Skanderup

Research Institute: GIS

Title of Paper: Comprehensive benchmarking of methods for mutation calling in circulating tumor DNA

Publish in: bioRxiv

Abstract: Detection of somatic mutations in cell-free DNA (cfDNA) is challenging due to low variant allele frequencies and pronounced DNA degradation. Here, we present a novel approach and resource for benchmarking of somatic variant calling algorithms in cfDNA samples from cancer patients. Using longitudinally collected cfDNA samples from colorectal and breast cancer patients, we identify patient-matched samples with high and ultra-low circulating tumor DNA (ctDNA) levels. These sample pairs, preserving patient-specific germline and somatic haematopoiesis variant backgrounds, were used to generate dilution series capturing characteristics of bona-fide cfDNA samples. To benchmark the accuracy and limit of detection of 9 somatic variant calling algorithms, we used deep Whole Genome Sequencing (WGS, 150x) and ultra-deep Whole Exome Sequencing (WES, 2,000x) to construct a reference set of ∼37,000 Single Nucleotide Variants and ∼58,000 Insertions/Deletions. We tested methods under variable ctDNA levels and depth of sequencing, generating guidelines for method choice depending on use case. Using a machine learning approach, we further evaluated the potential of fine-tuning individual variant callers, revealing features that may improve accuracy in cfDNA samples. Overall, we present a new resource for benchmarking of somatic variant calling methods in cfDNA, providing insights on method choice to realize the potential of liquid biopsies in precision oncology.

URL:  https://doi.org/10.1101/2025.02.16.638482 

18 Jan 2025

Submitted by (Bold are A*STAR Staff): Robert Laskowski, Jakub Mikula & Guglielmo Vastola

Research Institute: IHPC

Title of Paper: Understanding and control of gas porosity in metal laser powder-bed fusion additive manufacturing

Publish in: Computer Integrated Manufacturing

Abstract: The presented study discusses mechanism leading to gass porosity formation during additive manufacturing (AM) process. The method employs numerical scheme, which includes fluid dynamics of the melt pool and on-the-fly ray-tracing implemented within a phase field framework where the liquid/vapor interface is captured within volume of fluid approach. The emission of pores in the middle or the stripe happens only for relatively low scan speed (less than 0.6 m/s for IN718). The stripe edges (laser turning points) are identified as potential source of gas pores at scan speeds as high as 1 m/s. Simulations of laser turning, representative of the edge of a stripe, suggest the way the process parameters can be altered to avoid local porosity formation, while still ensuring a deep melt pool suitable for high build rates. The laser power modulation around the edge can lead to over 50% reduction of the pores emission. The proposed numerical framework requires only moderate computational resources, thus providing a holistic tool to decrease defect density and thus further improve quality of additive manufactured components.

URL:  https://doi.org/10.1080/0951192X.2025.2452984

14 Jan 2025

Submitted by (Bold are A*STAR Staff): Yingying Jiang, Zicong Marvin Wong, Hongwei Yan, Teck Leong Tan, Utkur Mirsaidov

Research Institute: IHPC

Title of Paper: Revealing Multistep Phase Separation in Metal Alloy Nanoparticles with In Situ Transmission Electron Microscopy

Publish in: ACS Nano

Abstract: Phase separation plays a crucial role in many natural and industrial processes, such as the formation of clouds and minerals and the distillation of crude oil. In metals and alloys, phase separation is an important approach often utilized to improve their mechanical strength for use in construction, automobile, and aerospace manufacturing. Despite its importance in many processes, the atomic details of phase separation are largely unknown. In particular, it is unclear how a different crystal phase emerges from the parent alloy. Here, using real-time in situ transmission electron microscopy, we describe the stages of the phase separation in face-centered cubic (fcc) AuRu alloy nanoparticles, resulting in a Ru phase with a hexagonal close-packed (hcp) crystal structure. Our observation reveals that the hcp Ru phase forms in two steps: the spinodal decomposition of the alloy produces metastable fcc Ru clusters, and as they grow larger, these clusters transform into hcp Ru domains. Our calculations indicate that the primary reason for the fcc-to-hcp transformation is the size-dependent competition between the interfacial and bulk energies of Ru domains. These insights into elusive, transient steps in the phase separation of alloys can aid in engineering nanomaterials with unconventional phases.

URL:  https://doi.org/10.1016/j.surfcoat.2025.131792

13 Jan 2025

Submitted by (Bold are A*STAR Staff): Haiyang Yu, Wenping Liang, Qiang Miao, Mengjuan Yin, Hongmei Jin, Yuanyuan Sun, Yuehao Xu, Xiangle Chang

Research Institute: IHPC

Title of Paper: Study on the wear resistance and thermodynamic stability of (MNbTaZrTi)N (M = Cr, Hf) high-entropy nitride coatings at elevated temperatures

Publish in: Surface and Coatings Technology

Abstract: One of the major challenges fac+G56ed by high-temperature titanium alloy components in applications is wear. Designing and preparing a highly wear-resistant coating remains a longstanding technical challenge. In this work, (MNbTaZrTi)N (M = Cr, Hf) high-entropy nitride coatings were developed on the basis of the (TaNbZr)N system using first-principles calculations. The effects of Cr and Hf on the thermodynamic stability and performance of nitride ceramics were systematically investigated. Additionally, (MNbTaZrTi)N high-entropy nitride coatings were applied to titanium alloy surfaces via the double-glow plasma surface alloying technique, followed by high-temperature friction and wear tests. Research findings revealed that the addition of Cr and Hf enhanced both the mechanical properties and thermodynamic stability of nitride ceramics. The (MNbTaZrTi)N high-entropy nitride ceramics exhibited better performance at high temperatures. Furthermore, the formed transition metal oxides at high temperatures significantly enhanced the friction performance of titanium alloy surfaces, leading to a tenfold reduction in the wear rate during ball-on-disc tests conducted at 700 °C (∼ 10−5 mm3/N•m). This study will offer valuable guidance for the design and creation of novel wear-resistant high-entropy nitride ceramic coatings.

URL:  https://doi.org/10.1016/j.surfcoat.2025.131792

18 Dec 2024

Submitted by (Bold are A*STAR Staff): Prasad Sarashetti, Josipa Lipovac, Filip Tomas, Mile Šikić & Jianjun Liu

Research Institute: GIS

Title of Paper: Evaluating data requirements for high-quality haplotype-resolved genomes for creating robust pangenome references

Publish in: Genome Biology

Abstract:

Background
Long-read technologies from Pacific Biosciences (PacBio) and Oxford Nanopore Technologies (ONT) have transformed genomics research by providing diverse data types like HiFi, Duplex, and ultra-long ONT. Despite recent strides in achieving haplotype-phased gapless genome assemblies using long-read technologies, concerns persist regarding the representation of genetic diversity, prompting the development of pangenome references. However, pangenome studies face challenges related to data types, volumes, and cost considerations for each assembled genome, while striving to maintain sensitivity. The absence of comprehensive guidance on optimal data selection exacerbates these challenges.

Results
Our study evaluates recommended data types and volumes required to establish a robust de novo genome assembly pipeline for population-level pangenome projects, extensively examining performance between ONT’s Duplex and PacBio HiFi datasets in the context of achieving high-quality phased genomes with enhanced contiguity and completeness. The results show that achieving chromosome-level haplotype-resolved assembly requires 20 × high-quality long reads such as PacBio HiFi or ONT Duplex, combined with 15–20 × of ultra-long ONT per haplotype and 10 × of long-range data such as Omni-C or Hi-C. High-quality long reads from both platforms yield assemblies with comparable contiguity, with HiFi excelling in phasing accuracies, while Duplex generates more T2T contigs.

Conclusion
Our study provides insights into optimal data types and volumes for robust de novo genome assembly in population-level pangenome projects. Reassessing the recommended data types and volumes in this study and aligning them with practical economic limitations are vital to the pangenome research community, contributing to their efforts and pushing genomic studies with broader impacts.

URL:  https://doi.org/10.1186/s13059-024-03452-y

10 Dec 2024

Submitted by (Bold are A*STAR Staff): Wenyu Zhou, Haisong Feng, Shihong Zhou, Mengxin Wang, Yuping Chen, Chenyang Lu, Hao Yuan, Jing Yang, Qun Li, Luxi Tan, Lichun Dong, Yong-Wei Zhang

Research Institute: IHPC

Title of Paper: Designing and screening single-atom alloy catalysts for CO2 reduction to CH3OH via DFT and machine learning

Publish in: Early View

Abstract: Carbon dioxide (CO2) utilization technology is of great significance for achieving carbon neutrality, in which the catalytic materials play crucial roles, and among them, single-atom alloys (SAAs) are of particular interests. In this study, density functional theory (DFT) calculations and machine learning are employed to assess the effectiveness of Cu-, Ag-, and Ni-host SAAs as catalysts for electrochemical CO2 reduction to CH3OH. The Gibbs free energies of 477 elementary reactions across 35 SAAs involved in CO2 reduction are calculated, and by utilizing this dataset, a trained gradient boosting regression model is established with an excellent accuracy. Subsequently, the properties of 46 unknown SAAs are predicted, including their pathways, products, potential-determining steps (PDS), and corresponding Gibbs free energies of the PDS (GPDS). Three promising candidates, ZnCu, AuAg and MoNi, stand out due to their lowest GPDS among Cu-, Ag- and Ni- hosted SAAs, respectively.

URL:  https://doi.org/10.1002/aic.18678

09 Dec 2024

Submitted by (Bold are A*STAR Staff): Lun-Hsin Kuo, Xu Ban, Jia-Hao He, Duc Nam Phuong Pham, Choon Wee Kee, Choon-Hong Tan

Research Institute: ISCE2

Title of Paper: A Quantitative Study of the Halogenophilic Nucleophilic Substitution (SN2X) Reaction and Chalcogenophilic Nucleophilic Substitution (SN2Ch) Reaction

Publish in: American Chemical Society

Abstract: Halogenophilic nucleophilic substitution (SN2X) has a distinctly different reaction pathway compared to the bimolecular nucleophilic substitution reaction (SN2), but they can lead to the same reaction product. However, their differences can be distinguished by studying stereoselective reactions in which both reaction pathways are possible. Herein, we utilize the stereospecific nature of SN2 and the presence of a pro-chiral anion intermediate in SN2X to conduct a quantitative study in which both SN2 and SN2X reactions exist. We developed a procedure supported by kinetic simulations to measure the halogenophilic percentage (X%). We also developed a new parameter, relative halogenophilicity (H), to quantify the intrinsic characteristics of SN2X reactions and found it to correlate well with the Hammett and Mayr postulates. We studied the time dependency of X% under different reaction conditions, which led to the discovery of two new distinct mechanisms: chalcogenophilic nucleophilic substitution (SN2Ch) reaction and bromide-catalyzed dynamic kinetic resolution. The SN2 and SN2X reactions exhibit similar behavior from both thermodynamic and kinetic perspectives, suggesting that they occur to varying degrees in most of the reactions. Consequently, they are inherently linked and should not be considered in isolation.

URL:  https://pubs.acs.org/doi/10.1021/jacs.4c12463

27 Nov 2024

Submitted by (Bold are A*STAR Staff): Haimei Wang, Hao Yuan, Wanwan Wang, Lei Shen, Jianguo Sun, Ximeng Liu, Jing Yang, Xingyang Wang, Tuo Wang, Ning Wen, Yulin Gao, Kepeng Song, Dairong Chen, Shijie Wang, Yong-Wei Zhang, John Wang

Research Institute: IHPC, IMRE

Title of Paper: Asymmetric Polarization Modulation of d–p Hybridization-Enhanced Bidirectional Sulfur Redox Kinetics with Heteronuclear Dual-Atom CatalystsClic

Publish in: ACS Nano

Abstract: Lithium sulfur batteries (LiSBs) represent a highly promising avenue for future energy storage systems, offering high energy density and eco-friendliness. However, the sluggish kinetics of the sulfur redox reaction (SRR) poses a significant challenge to their widespread applications. To tackle this challenge, we have developed an efficient heteronuclear dual-atom catalyst (hetero-DAC) that leverages surface charge polarization to enhance the asymmetric adsorption of sulfur intermediates. This study investigates how asymmetric electronic redistribution of CoFe DACs modulates the d–p orbital hybridization with sulfur intermediates, revealing the mechanisms of moderate adsorption dynamics with enhanced catalytic performance. The dynamic switching between mono and dual adsorption sites, enabled by the heteronuclear polarized configuration, fine-tunes the orbital hybridization, boosting the bidirectional rate-determining steps, that is, the solid–solid conversion of Li2S2 to Li2S and the reverse dissociation of Li2S. Consequently, the thus-designed CoFe DACs cathode delivers impressive rate performance, achieving a high initial specific capacity of 703.9 mA h g–1 at 3 C, with a negligible decay rate of only 0.031% over 1000 cycles, demonstrating sustained long-term cycling stability. This work bridges geometric configurations and electronic structures, elucidating the mechanisms of asymmetric trapping and conversion enabled by hetero-DACs and offering fresh perspectives for catalyst design in LiSBs and beyond.

URL:  https://pubs.acs.org/doi/10.1021/acsnano.4c09637

21 Nov 2024

Submitted by (Bold are A*STAR Staff): Elaine GY Chew, Zhehao Liu, Zheng Li, Sun Ju Chung, Michelle M. Lian, Moses Tandiono, Yue Jing Heng, Ebonne Y. Ng, Louis CS Tan, Wee Ling Chng, Tiak Ju Tan, Esther KL Peh, Ying Swan Ho, Xiao Yin Chen, Erin YT Lim, Chu Hua Chang, Jonavan J. Leong, Ting Xuan Peh, Ling Ling Chan, Yinxia Chao, Wing-Lok Au, Kumar M. Prakash, Jia Lun Lim, Yi Wen Tay,  Vincent Mok, Anne YY Chan, Juei-Jueng Lin, Beom S. Jeon, Kyuyoung Song, Clement C. Tham, Chi Pui Pang, Jeeyun Ahn, Kyu Hyung Park, Janey L. Wiggs, Tin Aung, Ai Huey Tan, Azlina Ahmad Annuar, Mary B. Makarious, Cornelis Blauwendraat, Mike A. Nalls, Laurie A. Robak, Roy N. Alcalay, Ziv Gan-Or, Richard Reynolds, Shen-Yang Lim, Yun Xia, Chiea Chuen Khor, Eng-King Tan, Zhenxun Wang,  Jia Nee Foo

Research Institute: GIS

Title of Paper: Exome sequencing in Asian populations identifies low-frequency and rare coding variation influencing Parkinson’s disease risk

Publish in: Nature Aging

Abstract: Parkinson’s disease (PD) is an incurable, progressive and common movement disorder that is increasing in incidence globally because of population aging. We hypothesized that the landscape of rare, protein-altering variants could provide further insights into disease pathogenesis. Here we performed whole-exome sequencing followed by gene-based tests on 4,298 PD cases and 5,512 controls of Asian ancestry. We showed that GBA1 and SMPD1 were significantly associated with PD risk, with replication in a further 5,585 PD cases and 5,642 controls. We further refined variant classification using in vitro assays and showed that SMPD1 variants with reduced enzymatic activity display the strongest association (<44% activity, odds ratio (OR) = 2.24, P = 1.25 × 10−15) with PD risk. Moreover, 80.5% of SMPD1 carriers harbored the Asian-specific p.Pro332Arg variant (OR = 2.16; P = 4.47 × 10−8). Our findings highlight the utility of performing exome sequencing in diverse ancestry groups to identify rare protein-altering variants in genes previously unassociated with disease.

URL:  https://doi.org/10.1038/s43587-024-00760-7

05 Nov 2024

Submitted by (Bold are A*STAR Staff): Damien K. J. Lee, Teck Leong Tan, Man-Fai Ng

Research Institute: IHPC

Title of Paper: Machine Learning-Assisted Bayesian Optimization for the Discovery of Effective Additives for Dendrite Suppression in Lithium Metal Batteries

Publish in: ACS Applied Materials & Interfaces

Abstract: In the pursuit of enhancing the performance and safety of lithium (Li)-metal batteries, the discovery of effective electrolyte additives to suppress Li dendrites has emerged as a paramount objective. In this study, we employ an inverse design strategy to identify potential additives for dendrite mitigation. Two key mechanisms, namely, the formation of robust solid electrolyte interphase layers and the leveling mechanism, serve as the foundation for our investigation. Our inverse design strategy is guided by molecular properties such as the lowest unoccupied molecular orbital energy and interaction energy upon Li surface adsorption. An active learning process utilizing Bayesian optimization (BO) was utilized to identify potential molecules with ideal properties. Through this screening process, we uncover a collection of 62 molecules with the potential to act as SEI-forming additives, along with 106 molecules for leveling additives, both surpassing the performance of established additives reported in the literature. This work highlights the potential of BO methods in computationally based inverse design of materials for many applications, and the discovered additives could potentially boost the commercialization of Li–metal batteries.

URL:  https://doi.org/10.1021/acsami.4c16611

30 Oct 2024

Submitted by (Bold are A*STAR Staff): Yuanjian Li, Xiang Feng, Gaoliang Yang, Wei Ying Lieu, Lin Fu, Chang Zhang, Zhenxiang Xing, Man-Fai Ng, Qianfan Zhang, Wei Liu, Jun Lu & Zhi Wei Seh 

Research Institute: IMRE, IHPC

Title of Paper: Toward waterproof magnesium metal anodes by uncovering water-induced passivation and drawing water-tolerant interphases

Publish in: Nature Communications

Abstract: Magnesium (Mg) metal is a promising anode candidate for high-energy and cost-effective multivalent metal batteries, but suffers from severe surface passivation in conventional electrolytes, especially aqueous solutions. Here, we uncover that MgH2, in addition to the well-known MgO and Mg(OH)2, can be formed during the passivation of Mg by water. The formation mechanism and spatial distribution of MgH2, and its detrimental effect on interfacial dynamics and stability of Mg anode are revealed by comprehensive experimental and theoretical investigations. Furthermore, a graphite-based hydrophobic and Mg2+-permeable water-tolerant interphase is drawn using a pencil on the surface of Mg anodes, allowing them to cycle stably in symmetric (> 900 h) and full cells (> 500 cycles) even after contact with water. The mechanistic understanding of MgH2-involved Mg passivation and the design of pencil-drawn waterproof Mg anodes may inspire the further development of Mg metal batteries with high water resistance.

URL:  https://doi.org/10.1038/s41467-024-53796-z

30 Oct 2024

Submitted by (Bold are A*STAR Staff): Thathsara D. Maddumapatabandi, Fabio Bussolotti, Wei Fu, Hiroyo Kawai, Kuan Eng Johnson Goh

Research Institute: IMRE, IHPC

Title of Paper: Influence of Substrate Defects on the Electronic Properties of the WS2 Monolayer/Highly Oriented Pyrolytic Graphite Heterostructure

Publish in: ACS Applied Electronic Materials

Abstract: This study investigates the influence of local defects introduced in highly oriented pyrolytic graphite (HOPG) substrates on the electronic properties of two-dimensional transition-metal dichalcogenides (TMDs). Utilizing a combination of X-ray photoelectron spectroscopy (XPS) and angle-resolved photoemission spectroscopy (ARPES), we studied the changes in energy level alignment and interface charge transfer phenomena at the HOPG/WS2 interface. While XPS did not detect significant spectral changes for defect densities up to ∼7%, ARPES line shape analysis revealed that the increased defect density in the HOPG interfacing the WS2 monolayer significantly shortened carrier lifetimes. This provides crucial guidance for the study and optimization of devices wherein TMDs are interfaced with a HOPG or graphene.

URL:  https://doi.org/10.1021/acsaelm.4c01330

17 Oct 2024

Submitted by (Bold are A*STAR Staff): Zaohong Zhang, Kaihui Xu, Jing Yang, Zhuoyu Ji , Yunchen Ge, Zhicong Shi, Yongwei Zhang, Kai Zhang, Chuan Wu, and Jia Hong Pan

Research Institute: IHPC

Title of Paper: Versatility of π-d Conjugated Coordination Nickel Metal-Organic Frameworks as Electrode Materials of Metal-Ion Batteries

Publish in: Energy Material Advances

Abstract: Metal–organic frameworks have emerged as promising electrode materials for metal-ion batteries due to their superior structural customizability. However, they face challenges such as poor reversibility and easy degradation during electrochemical redox processes. Here, we report the synthesis of π-d conjugated coordination polymers through NH3-vapor-assisted self-polymerization of NiCl2·6H2O with 1,2,4,5-benzenetetramine tetrahydrochloride (namely, Ni-BTA). The synthesized Ni-BTA exhibits an open lattice structure that enhances the capacity for metal-ion diffusion, ensuring prolonged electrochemical cycling stability. Moreover, electrochemical characterizations reveal that Ni-BTA functions as a bifunctional material, serving as both cathode and anode materials for lithium-ion batteries (LIBs). After 1,000 cycles at 1.0 A g−1, the cathode and anode show high discharge capacities of 199.7 and 338.4 mAh g−1, respectively. Additionally, symmetrical all-organic batteries constructed with Ni-BTA exhibit a high specific capacity of 30.6 mAh g–1 and an ultrastable coulombic efficiency of approximately ≈100% after 6,000 cycles at 1.0 A g−1. Furthermore, Ni-BTA exhibits versatility as a robust cathode for aluminum ion batteries (AIBs), delivering a discharge capacity of 18.7 mAh g−1 after 10,000 cycles at 1.0 A g−1. These findings highlight the potential of Ni-BTA as a versatile and durable electrode materials for both LIBs and AIBs.

URL:  https://spj.science.org/doi/10.34133/energymatadv.0126

14 Oct 2024

Submitted by (Bold are A*STAR Staff): Choon Wee Kee, Jia’E Zheng, Wei Jie Yap, Roy Ou Yong and Yan Liu 

Research Institute: ISCE2

Title of Paper: Thermal and Sono—Aqueous Reforming of Alcohols for Sustainable Hydrogen Production

Publish in: Molecules 

Abstract: Hydrogen is a clean-burning fuel with water as its only by-product, yet its widespread adoption is hampered by logistical challenges. Liquid organic hydrogen carriers, such as alcohols from sustainable sources, can be converted to hydrogen through aqueous-phase reforming (APR), a promising technology that bypasses the energy-intensive vaporization of feedstocks. However, the hydrothermal conditions of APR pose significant challenges to catalyst stability, which is crucial for its industrial deployment. This review focuses on the stability of catalysts in APR, particularly in sustaining hydrogen production over extended durations or multiple reaction cycles. Additionally, we explore the potential of ultrasound-assisted APR, where sonolysis enables hydrogen production without external heating. Although the technological readiness of ultrasound-assisted or -induced APR currently trails behind thermal APR, the development of catalysts optimized for ultrasound use may unlock new possibilities in the efficient hydrogen production from alcohols.

URL:  https://doi.org/10.3390/molecules29204867

28 Aug 2024

Submitted by (Bold are A*STAR Staff): Mudi Li, Yaxi Ding, Prof. Siwen Zhang, Minghui Liu, Jiazhuo Li, Ying Sun, Dr. Lingfeng Zhu, Dr. Hui Li, Prof. Zhi Gen Yu, Prof. Yong-Wei Zhang, Prof. Hongge Pan, Prof. Bosi Yin, Prof. Tianyi Ma

Research Institute: IHPC

Title of Paper: Organic-Inorganic Coupling Strategy: Clamp Effect to Capture Mg2+ for Aqueous Magnesium Ion Capacitor

Publish in: German Chemical Society

Abstract: The rapid transport kinetics of divalent magnesium ions are crucial for achieving distinguished performance in aqueous magnesium-ion battery-based energy storage capacitors. However, the strong electrostatic interaction between Mg2+ with double charges and the host material significantly restricts Mg2+ diffusivity. In this study, a new composite material, EDA-Mn2O3, with double-energy storage mechanisms comprising an organic phase (ethylenediamine, EDA) and an inorganic phase (manganese sesquioxide) was successfully synthesized via an organic–inorganic coupling strategy. Inorganic-phase Mn2O3 serves as a scaffold structure, enabling the stable and reversible intercalation/deintercalation of magnesium ions. The organic phase EDA adsorbed onto the surface of Mn2O3 as an elastic matrix, works synergistically with Mn2O3, and utilizes bidentate chelating ligands to capture Mg2+. The robust coordination effect of terminal biprotonic amine in EDA enhances the structural diversity and specific capacity characteristics of the composite material, as further corroborated by density functional theory (DFT) calculations, ex situ XRD, XPS, and Raman spectroscopy. As expected, the EDA-Mn2O3 composite achieved an outstanding specific discharge capacity of 188.97 mAh/g at 0.1 A/g. Additionally, an aqueous magnesium ion capacitor with EDA-Mn2O3 serving as the cathode can reach 110.17 Wh/kg, which stands out among the aqueous magnesium ion capacitors that have been reported thus far. The abundant reversible redox sites are ensured by the strategic design concept based on the synergistic structure and composition advantages of organic and inorganic phases. This study aimed to explore the practical application value of organic-inorganic composite electrodes with double-energy storage mechanisms.

URL:  https://doi.org/10.1002/anie.202412735

21 Aug 2024

Submitted by (Bold are A*STAR Staff): Syed Zulfiqar Hussain Shah, Zainul Aabdin, Weng Weei Tjiu, Wei Nong, Jose Recatala-Gomez, Vijila Chellappan, Wenhao Zhai, Durga Venkata Maheswar Repaka, Gang Wu, Kedar Hippalgaonkar, Iris Nandhakumar, Pawan Kumar

Research Institute: IMRE, IHPC

Title of Paper: Thermoelectric Property Enhancement of Tellurium Nanowires by Surface Passivation

Publish in: ACS Applied Materials & Interfaces

Abstract: The pursuit of high-performance thermoelectric materials is of paramount importance in addressing energy sustainability and environmental concerns. Here, we explore the multifaceted impact of sulfur passivation in the matrix of tellurium nanowires (TeNWs), encompassing environmental control, thermoelectric properties, and charge carrier mobility. In this study, we present the facile production of TeNWs using an aqueous solution synthesis approach. The synthesized TeNWs were subsequently subjected to surface modification involving sulfur moieties. Our findings demonstrate that sulfur passivation not only effectively safeguards the nanowires from environmental degradation but also significantly augments their thermoelectric properties. Notably, the highest recorded values were achieved at 560 K for passivated tellurium nanowires, exhibiting a Seebeck coefficient of 246 μV/K, an electrical conductivity of 14.2 S/cm, and power factors of 86.7 μW/m-K2. This strategy presents a promising avenue for the development of advanced thermoelectric materials for applications in energy harvesting, waste heat recovery, and sustainable energy conversion technologies.

URL:  https://pubs.acs.org/doi/10.1021/acsami.4c02469

15 Aug 2024

Submitted by (Bold are A*STAR Staff): Yuanyuan Feng, Jing Yang, Maykel Manawan, Huiyun Gan, Dongwei Ma, Zhuoyu Ji, Zhicong Shi, Zhongzhu Liu, Yong-Wei Zhang, Chuan Wu, Jia Hong Pan

Research Institute: IHPC

Title of Paper: Comparative insight into crystal evolutions of monodisperse MNb2O6 (M = Ni, Cu, Zn) spheres during electrochemical cycling in Li/Al-ion batteries

Publish in: Energy Storage

Abstract: Niobates have emerged as advanced anode materials for lithium-ion batteries, owing to their inherently higher voltage and the occurrence of multiple one-electron redox reactions. However, there is a lack of comprehensive comparative analysis regarding their performance in lithium-ion and aluminum-ion battery applications. In this study, a facile solvothermal process is developed to synthesize uniform submicrospheres of three niobates: NiNb2O6, CuNb2O6, and ZnNb2O6 with large specific surface area and narrow size distribution. Their superior textural properties consisting of interconnected nanograins offer numerous active sites, delivering enhanced capacity and rate performance for the constructed half and full cells. Our in-situ XRD analysis reveals that all three niobates exhibit ultralow crystal volume expansion (< 6 %). But they exhibit distinct ion storage mechanisms: CuNb2O6 undergoes a phase transition to LiNb3O8 and NbO2 upon cyclic insertion of Li+ ions; NiNb2O6 mainly involves a classic hybrid-controlled process, facilitating easy ion insertion/extraction into/from the crystal lattices, especially at low sweep rates; while ZnNb2O6 stores charges via a pseudocapacitive-controlled process. Density functional theory (DFT) calculation and ex-situ XRD analysis confirm that CuNb2O6 outperforms the others, displaying the best electrochemical performance and holding promise as a high-energy electrode material thanks to favorable phase conversion, enhanced transport channels, porous structure and spherical morphology.

URL:  https://doi.org/10.1016/j.est.2024.113187

14 Aug 2024

Submitted by (Bold are A*STAR Staff): Song Lin Zhang, Yuke Li, Jintao Zhang, Wanwan Wang, Nguk Neng Tham, Bing Li, Jia Zhang, Zhaolin Liu

Research Institute: IHPC, IMRE

Title of Paper: Anchoring Metal–Nitrogen Sites on Porous Carbon Polyhedra with Highly Accessible Multichannels for Efficient Oxygen Reduction

Publish in: ACS Applied Materials & Interfaces

Abstract: Transition metal–nitrogen-carbon complexes, featuring single metal atoms embedded in a nitrogen-doped carbon matrix, emerge as promising alternatives to traditional platinum-based catalysts, offering cost-effectiveness, abundance, and enhanced catalytic performance. This work introduces a novel method for the etching and doping of zeolitic imidazolate frameworks (ZIFs) with transition metals, creating a uniform distribution of secondary metal centers on ZIF surfaces. By disrupting the crystalline symmetry of ZIFs through synthetic defect engineering, we gain access to their entire internal volume, creating multichannel pathways. The absorption of metal ions is theoretically simulated, demonstrating their thermodynamically spontaneous nature. The selective removal of defect channels under Lewis acidic conditions, induced by metal ion alcoholysis/hydrolysis, facilitates the introduction of metal atoms into ZIF cavities. The resulting single-atom catalyst, after pyrolysis, features a three-dimensional (3D) multichannel structure, high surface area, and uniformly dispersed metal atoms within the N-doped carbon matrix, establishing it as an exceptional catalyst for the oxygen reduction reaction (ORR). Our findings highlight the potential of using metal etching in defect-engineered metal–organic frameworks (MOFs) for single-atom catalyst preparation, paving the way for the next generation of high-performance, cost-effective ORR catalysts in sustainable energy systems.

URL:  https://doi.org/10.1021/acsami.4c07385

06 Aug 2024

Submitted by (Bold are A*STAR Staff): Miao Tian, Jing Lyu, Ran Su, Xu Zhang, Kexin Wang, Xiang Lv, Dawei Zhang, Shuo-Wang Yang, John Hon Kay Yip, Zhongkai Hao, Guo Qin Xu

Research Institute: IHPC

Title of Paper: Harnessing the Power of Nano-Ferroelectrics: BaTiO3/MXene (Ti3C2Tx) Composites for Enhanced Lithium Storage

Publish in: Advanced Energy Materials

Abstract: 2D Ti3C2Tx MXene is a desirable electrode material for advanced lithium-ion batteries (LIBs) in the pursuit of high energy and power densities, owing to its extensive reactive area and surface-induced pseudo-capacitance. Here, a novel synergistic strategy for fortifying lithium storage capability is first proposed, by in-situ anchoring BaTiO3 ferroelectric nanoparticles on few-layered Ti3C2Tx nanosheets (BT/f-Ti3C2Tx) using a hydrothermal method. The uniform BaTiO3 nanoparticles effectively prevent the restacking of Ti3C2Tx nanosheets, successfully deplete metastable Ti atoms, and intriguingly form a thin and well-adhered solid electrolyte interface layer, enhancing the aggregation-resistant, oxidation-resistant, and electrochemical properties of Ti3C2Tx. Simultaneously, the internal electric fields, originating from the spontaneous polarization of BaTiO3 ferroelectric nanoparticles, can augment the adsorption of Li+, boosting the lithium storage capacity and reaction kinetics. The resulting composite electrode displays a remarkable charge capacity of 84 mAh g−1 at 10 A g−1, almost five times that of pristine Ti3C2Tx electrode. The excellent rate performance and cyclability make BT/f-Ti3C2Tx composites highly attractive for LIBs. Furthermore, this synthetic approach presented here is scalable and can be extended to other Ti-based materials. This strategy is expected to underscore the considerable potential of ferroelectric composites for integration into high-performance LIBs.

URL:  https://doi.org/10.1002/aenm.202401988

03 Aug 2024

Submitted by (Bold are A*STAR Staff): Ganna Petruk , Jitka Petrlova, Firdaus Samsudin, Peter J. Bond, Artur Schmidtchen

Research Institute: BII

Title of Paper: Thrombin-derived C-terminal peptides bind and form aggregates with sulfated glycosaminoglycans

Publish in: Heliyon

Abstract: Glycosaminoglycans (GAGs) such as heparin and heparan sulfate (HS) play crucial roles in inflammation and wound healing, serving as regulators of growth factors and pro-inflammatory mediators. In this study, we investigated the influence of heparin/HS on thrombin proteolysis and its interaction with the generated 11 kDa thrombin-derived C-terminal peptides (TCPs). Employing various biochemical and biophysical methods, we demonstrated that 11 kDa TCPs aggregate in the presence of GAGs, including heparin, heparan sulfate, and chondroitin sulfate-B. Circular dichroism analysis demonstrated that 11 kDa TCPs, in the presence of GAGs, adopt a β-sheet structure, a finding supported by thioflavin T1 (ThT) fluorescence measurements and visualization of 11 kDa TCP-heparin complexes using transmission electron microscopy (TEM). Furthermore, our investigations revealed a stronger binding affinity between 11 kDa TCPs and GAGs with higher sulfate group contents. Congruently, in silico simulations showed that interactions between 11 kDa TCPs and heparin/HS are predominantly electrostatic in nature. Collectively, our study suggests that 11 kDa TCPs have the capacity to aggregate in the presence of GAGs, shedding light on their potential roles in inflammation and wound healing.

URL:  https://doi.org/10.1016/j.heliyon.2024.e35703

28 Mar 2023

Submitted by (Bold are A*STAR Staff): Naythan Z. X. Yeo, Dillon W. P. Tay, Shi Jun Ang

Research Institute: ISCE2,IHPC

Title of Paper: Benchmarking tandem mass spectra of small natural product molecules via ab initio molecular dynamics

Published in: ChemRxiv

Abstract: Natural products have proven to be valuable, particularly in the fields of drug discovery and chemogenomics. Tandem mass spectrometry, along with reference mass spectral libraries, has been frequently used to assist the characterization of natural products present in unknown complex mixtures. As current spectral libraries only contain a small percentage of known natural products, their continual expansion is crucial for accurate molecular identification. However, doing so through experimental means is often expensive and time-consuming. This study explores the use of ab initio molecular dynamics simulations (AIMD) based on the lightweight GFN2-xTB semiempirical Hamiltonian, to generate mass spectra for small natural products molecules. Through this approach, more than 2,700 unique mass spectra were generated and analysed in relation to the Global Natural Products Social Molecular Networking (GNPS) database. This study found that AIMD performs relative well (mean cosine similarity score of 0.68), with improved performance observed in aromatic molecules but limitations found when applied to molecules with carboxylic acid groups. Other key findings relating to experimental and simulated conditions also led to several recommendations for future work in this area. Overall, AIMD proved to have huge potential to be used to develop a putative natural product mass spectral library.

URL: https://doi.org/10.26434/chemrxiv-2023-7k5x8