ChemRxiv最新文献

{"title":"Hydration Shell Water Surrounding Citrate-Stabilised Gold Nanoparticles","authors":"Martin, Rabe, Taritra, Mukherjee","doi":"10.26434/chemrxiv-2024-1dchd","DOIUrl":"https://doi.org/10.26434/chemrxiv-2024-1dchd","url":null,"abstract":"Presence of gold nanoparticles in an aqueous dispersion perturbs water molecules in their vicinity. Such water molecules form what is known as hydration shell and possess different vibrational attributes than those in the bulk dispersion. Raman spectroscopy was utilised to study these hydration shell water molecules around citrate-stabilised gold nanoparticles. Aqueous dilution series of three sizes of gold nanoparticle samples were prepared. Hydration shell spectral response, recovered by applying multivariate curve resolution technique, were compared against the spectra of the bulk phase. Once correlated with an increasing aqueous content in the respective samples, it could be inferred from the comparison that the hydration shell contains a less extensive hydrogen-bonding network with a smaller number of hydrogen-bonding interactions being possible than that in bulk. The results also suggest the hydrogen-bonding network in the hydration shells to be structurally more rigid and stronger, if compared against the intermolecular hydrogen-bonding prevalent in bulk.","PeriodicalId":9813,"journal":{"name":"ChemRxiv","volume":"49 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nuclease-resistant photo-responsive synthetic “double-stranded DNAzyme”","authors":"Subinoy, Rana, Alisha, Kamra, Rohit, Kapila, Bhaskar, Sen","doi":"10.26434/chemrxiv-2024-0167h","DOIUrl":"https://doi.org/10.26434/chemrxiv-2024-0167h","url":null,"abstract":"DNA nanotechnology has significantly progressed from basic structural designs to advanced practical applications. The inherent ability of DNA to assemble with small molecules has elevated it to the forefront of biological applications such as biosensing, bioimaging, altering cell behaviour, and therapeutic delivery. Deoxyribozymes (DNAzymes) represent catalytically active DNA molecules, which are essential yet uncommon, making the fabrication of synthetic DNAzymes significant. However, a key challenge in employing DNAzyme nanostructures in biological settings is their susceptibility to degradation by nucleases in the biological milieu. Herein, we introduced a hierarchical assembly of DNA and guanidium containing Pt(II)-complex (Pt G) through supramolecular interactions that display significant resistance to nucleases in human serum. The one-dimensional growth of the supramolecular structures leads to metal-metal bonds that impart luminescence properties with long-lived excited states. Light-mediated singlet oxygen generated from the Pt G·DNA system allows the oxidation of substrates similar to oxidase enzymes. Besides a fundamental understanding of the new hierarchical assembly, the study presents important functional aspects, including the nuclease resistance, robustness, specific oxidase-like function and on-demand light stimulus-dependent activity for practical applications.","PeriodicalId":9813,"journal":{"name":"ChemRxiv","volume":"49 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unprecedented Photoinduced-Electron-Transfer Probe with a Turn-ON Chemiluminescence Mode-of-Action","authors":"Doron, Shabat, Maya, David, Sara, Gutkin, Raj V., Nithun, Muhammad, Jbara","doi":"10.26434/chemrxiv-2024-vj8f6","DOIUrl":"https://doi.org/10.26434/chemrxiv-2024-vj8f6","url":null,"abstract":"PeT-based fluorescent probes were demonstrated to be powerful tools for detection and imaging, owing to their significant fluorescence enhancement in response to specific targets. While numerous examples of fluorescence-based PeT have been frequently reported, there is not even a single example of a PeT probe that operates via a chemiluminescence mode. Here we report the first PeT-based turn-on probe that acts via a chemiluminescent operation mode. We designed, synthesized, and evaluated a novel chemiluminescent probe, featuring a PeT-based turn-on mechanism. The probe consists of a phenoxy-1,2-dioxetane, linked to an azide unit that acts as a PeT quencher. Upon cycloaddition of a strained cycloalkyne with the azide, a triazole-dioxetane is formed, which undergoes relatively slow chemiexcitation, resulting in a measurement window with an exceptionally high signal-to-noise ratio (over 5000-fold). The PeT-dioxetane probe could effectively detect and image two model proteins labeled with strained cycloalkyne units (Myc-DBCO and Max-DBCO) through either NHS or maleimide conjugations. Comparative analysis shows that our PeT-based chemiluminescent probe significantly outperforms a commercially available fluorescent analog. We anticipate that the insights gained from this study will facilitate the development of additional chemiluminescent probes utilizing various PeT-quenching pathways.","PeriodicalId":9813,"journal":{"name":"ChemRxiv","volume":"189 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Equilibrium and Non-equilibrium Ensemble Methods for Accurate, Precise and Reproducible Absolute Binding Free Energy Calculations","authors":"Agastya Prakash, Bhati, Shunzhou, Wan, Peter V., Coveney","doi":"10.26434/chemrxiv-2024-sslzp-v2","DOIUrl":"https://doi.org/10.26434/chemrxiv-2024-sslzp-v2","url":null,"abstract":"Free energy calculations for protein-ligand complexes have become widespread in recent years owing to several conceptual, methodological and technological advances. Central among these is the use of ensemble methods which permits accurate, precise and reproducible predictions and are necessary for uncertainty quantification. Absolute binding free energies (ABFEs) are challenging to predict using alchemical methods and their routine application in drug discovery has remained out of reach until now. Here, we apply ensemble alchemical ABFE methods to a large dataset comprising 219 ligand-protein complexes and obtain statistically robust results with high accuracy (< 1 kcal/mol). We compare equilibrium and non-equilibrium methods for ABFE predictions at large scale and provide a systematic critical assessment of each method. The equilibrium method is more accurate, precise, faster, computationally more cost-effective and requires a much simpler protocol, making it preferable for large scale and blind applications. We find that the calculated free energy distributions are non-normal and discuss the consequences. We recommend a definitive protocol to perform ABFE calculations optimally. Using this protocol, it is possible to perform thousands of ABFE calculations within a few hours on modern exascale machines.","PeriodicalId":9813,"journal":{"name":"ChemRxiv","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-selective antagonists acting at a stable cell-cell interface have the potential to induce signaling","authors":"John, Proudfoot","doi":"10.26434/chemrxiv-2024-9kfl4","DOIUrl":"https://doi.org/10.26434/chemrxiv-2024-9kfl4","url":null,"abstract":"A model, based on receptor occupancy theory, for signaling due to receptor A and co-receptor B colocalization in the presence of a stable cell-cell interface reveals that a non-selective antagonist of receptor A with affinity for a receptor C on the trans-cell can induce as well as inhibit the signal due to A. As a result, assertion of selectivity for agents acting in such a system should be supported by measurement of signal when the co-receptor B is absent. For conditions where the co-receptor B is non-functional, the model reveals the potential to rescue function through bifunctional ligands, such as bispecific antibodies, antibody conjugates or even bifunctional tethered small molecules.","PeriodicalId":9813,"journal":{"name":"ChemRxiv","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemiluminescence signature arrays coupling with machine learning for Alzheimer’s disease serum diagnosis","authors":"Chongzhao, Ran, Biyue, Zhu, Yanbo, Li, Jing, Zhang, Jun, Yang, Shi, Kuang, Johnson, Wang, Shiqian, Shen, Xuan, Zhai, Jiajun, Xie, Astra, Yu","doi":"10.26434/chemrxiv-2024-vs1m9","DOIUrl":"https://doi.org/10.26434/chemrxiv-2024-vs1m9","url":null,"abstract":"Tremendous efforts have been made to directly identify serum components using traditional omics approaches. However, several unmet medical needs persist, particularly for chronic diseases that lack reliable biomarkers. The subtle physicochemical abnormality of serum has been widely overlooked and currently lacks detection methods. Inspired by the bat echolocation mechanism, we proposed a chemiluminescence “echoes” approach to depict the disease-specific signatures in biofluids. Specifically, Alzheimer’s disease (AD) serums were used for proof-of-concept study. We first demonstrated the discrepancy in physicochemical properties between AD and healthy control (HC) serums. On this basis, we developed a simple, fast and versatile UNICODE (UNiversal Interaction of Chemiluminescence echOes for Disease Evaluation) array for AD diagnosis. By employing a \"bat\" probe (ADLumin-1), which generates chemiluminescence autonomously, and combined with a panel of “flag” molecules that enable “echo” formation, we were able to create distinct signatures for various serum components and subtle physicochemical environments. To develop an AD-specific UNICODE diagnosis, we screened a library of over 1000 small molecules, and identified 12 “flag” molecules (top-12) that optimally depict the differences between AD and HC serums. Finally, we used the top-12 array for AD diagnosis. By modeling the UNICODE signatures with seven machine learning methods, we successfully differentiated AD (n = 31) and HC (n = 37) serums, and our best model of random forest provided accuracy = 85.48%, precision = 85.00%, recall = 88.60%, f1 = 85.63%, and AUC = 90.24%. Our strategy could provide new insights into biofluid abnormality and prototype tools for developing liquid biopsy diagnoses for AD and other diseases.","PeriodicalId":9813,"journal":{"name":"ChemRxiv","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergetic hydrogen-bond network of functionalized graphene and cations for enhanced atmospheric water capture","authors":"Rakesh, Joshi, Xiaojun, Ren, Xiao, Sui, Llewellyn, Owens, Dali, Ji, Xinyue, Wen, Yuta, Nishina, Kamal , Pant, Vanesa, Quintano, Daria , Andreeva, Kostya, Novoselov, Amir, Karton, Tobias, Foller, Daisuke, Asanoma","doi":"10.26434/chemrxiv-2024-m9f3h-v2","DOIUrl":"https://doi.org/10.26434/chemrxiv-2024-m9f3h-v2","url":null,"abstract":"Water molecules at the solid-liquid interface display intricate behaviours sensitive to small changes. The presence of different interfacial components, such as cations or functional groups, shape the physical and chemical properties of the hydrogen bond network. Understanding such interfacial hydrogen-bond networks is essential for a large range of applications and scientific questions. To probe the interfacial hydrogen-bond network, atmospheric water capture is a powerful tool. Here, we experimentally observe that a calcium ion on a calcium-intercalated graphene oxide aerogel (Ca-GOA) surface captures 3.2 times more water molecules than in its freestanding state. From experimental Van’t Hoff estimation and density functional theory (DFT) calculations, we uncover the synergistically enhanced hydrogen-bond network of the calcium ion-epoxide complex due to significantly larger polarizations and hydrogen bond enthalpies. This study reveals valuable insights into the interfacial water hydrogen-bond network on functionalized carbon-cation complexed surfaces and potential pathways for future atmospheric water generation technologies.","PeriodicalId":9813,"journal":{"name":"ChemRxiv","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temperature Correction of Near-Infrared Spectra of Raw Milk","authors":"José Antonio, Díaz Olivares, Stef, Grauwels, Xinyue, Fu, Ines, Adriaens, Wouter, Saeys, Ryad, Bendoula, Jean-Michel, Roger, Ben, Aernouts","doi":"10.26434/chemrxiv-2024-ls0j0","DOIUrl":"https://doi.org/10.26434/chemrxiv-2024-ls0j0","url":null,"abstract":"Accurate milk composition analysis is crucial for improving product quality, economic efficiency, and animal health in the dairy industry. Near-infrared (NIR) spectroscopy can quantify milk composition quickly and nondestructively. However, external factors, such as temperature fluctuations, can alter the molecular vibrations and hydrogen bonding in milk, altering the NIR spectra and leading to errors in predicting key constituents such as fat, protein, and lactose. This study compares the effectiveness of Piecewise Direct Standardization (PDS), Continuous PDS (CPDS), External Parameter Orthogonalization (EPO), and Dynamic Orthogonal Projection (DOP in correcting the impact of temperature-induced variations on predictions in milk long-wave NIR spectra (LW-NIR, 1000 to 1700 nm).\u0000A total of 270 raw milk samples were analyzed, collecting both reflectance and transmittance spectra at five different temperatures (20°C, 25°C, 30°C, 35°C, and 40°C). The experimental setup ensured precise temperature control and accurate spectral measurements. PLSR models were calibrated at 30°C to predict milk fat, protein, and lactose content. The performance of these models was assessed before and after applying the temperature correction methods, with a primary focus on reflectance spectra.\u0000Results indicate that EPO and DOP significantly enhance model robustness and prediction accuracy across all temperatures, outperforming PDS and CPDS, especially for lactose prediction. These orthogonalization methods were compared against PLSR models calibrated with spectra from all temperatures. EPO and DOP showed comparable or superior performance, highlighting their effectiveness without requiring extensive temperature-specific calibration data. These findings suggest that orthogonalization methods are particularly suitable for in-line milk quality measurements under farm conditions where temperature control is challenging. This study highlights the potential of advanced chemometric techniques to improve real- time, on-farm milk composition analysis, facilitating better farm management and enhanced dairy product quality.","PeriodicalId":9813,"journal":{"name":"ChemRxiv","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating Path Sampling with Enhanced Sampling for Rare-event Kinetics","authors":"Dhiman, Ray","doi":"10.26434/chemrxiv-2024-qr6kv","DOIUrl":"https://doi.org/10.26434/chemrxiv-2024-qr6kv","url":null,"abstract":"Studying the kinetics of long-timescale rare events is a fundamental challenge in molecular simulation. To address this problem, we propose an integration of two different rare-event sampling philosophies: biased enhanced sampling and unbiased path sampling. Enhanced sampling methods e.g. metadynamics can facilitate enthalpic barrier crossing by applying an external bias potential. On the contrary, path sampling methods like weighted ensemble (WE) lack explicit mechanisms to overcome energetic barriers. However, they can accelerate the exploration of rugged free energy surfaces through trajectory resampling. We show that a judicious combination of the weighted ensemble with a metadynamics-like algorithm, can synergize the strengths and mitigate the deficiencies of path sampling and enhanced sampling approaches. The resulting integrated sampling (IS) algorithm improves the computational efficiency of calculating the kinetics of peptide conformational transitions, protein unfolding, and the dissociation of a ligand-receptor complex. Furthermore, the IS approach can direct sampling along the minimum free energy pathway even when the collective variable used for biasing is suboptimal. These advantages make the integrated sampling algorithm suitable for studying the kinetics of complex molecular systems of biological and pharmaceutical relevance.","PeriodicalId":9813,"journal":{"name":"ChemRxiv","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An integral activity-based protein profiling (IABPP) method for higher throughput determination of protein target sensitivity to small molecules","authors":"Vivian S., Lin, Aaron T., Wright, Stephen J., Callister, Leo J., Gorham, Gerard X., Lomas, Agne, Sveistyte, John T., Melchior, Priscila M., Lalli, Chathuri J., Kombala, Tong, Zhang, Vanessa L., Paurus","doi":"10.26434/chemrxiv-2024-jg6bn","DOIUrl":"https://doi.org/10.26434/chemrxiv-2024-jg6bn","url":null,"abstract":"Activity-based protein profiling (ABPP) is a chemoproteomic technique that uses chemical probes to label active enzymes selectively and covalently in complex proteomes. Competitive ABPP, which involves treatment of the active proteome with an analyte of interest, is especially powerful for profiling how small molecules impact specific protein activities. Advances in higher throughput workflows have made it possible to generate extensive competitive ABPP data across various biological systems and treatments, making this approach highly appealing for characterizing shared and unique proteins affected by perturbations such as drug or chemical exposures. To use the competitive ABPP approach effectively to understand potential adverse effects of chemicals of concern, a wide range of concentrations may be needed, particularly for chemicals that may lack toxicity data. In this work, we present an integral competitive ABPP method that enables target sensitivity differentiation across a wide range of concentrations for the model organophosphate (OP), paraoxon. Using previously developed OP-ABPs, we optimized conditions for tandem mass tag (TMT) multiplexing of ABPP samples and compared conventional competitive ABPP involving discrete samples at various paraoxon concentrations with pooling of samples across that same concentration range. The results show that small vs. large differences in integral intensities for the competitive sample can be used to distinguish low vs. high sensitivity proteins, respectively, without increasing the overall number of samples. We envision the integral ABPP method will provides a means to screen diverse chemicals more rapidly to identify both highly sensitive and less sensitive protein targets.","PeriodicalId":9813,"journal":{"name":"ChemRxiv","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}