dataesr/scientific-paragraphs-categorization huggingface dataset:
Materials Reagents and solvents were obtained from commercial suppliers and used without further purification. Column chromatography was carried out using Merck Kieselgel 60 silica gel (particle size: 32-63 Å). Analytical TLC was performed using Merck precoated silica gel 60 F-254 sheets. All the C-H activation reactions were carried out under a nitrogen atmosphere. NMR spectroscopic data were acquired on Bruker Avance III spectrometer at 500 MHz for 1 H-NMR and 125 MHz for 13 C-NMR. HR-MS spectra were recorded on a 6500 series Q-TOF (Agilent) spectrometer. UV-Vis absorption spectra was measured on the UV-Vis Cary 60-Agilent spectrometer. Fluorescence spectra were recorded on Perkin Elmer FL 8500 spectrometer.
Acknowledgements This work was supported by the  European Research Council   ERC Consolidator grant  BrightSens  648528. B. A. was supported by  LabEx Chimie des Systèmes Complexes. I. O. A. acknowledges support from  Marie Curie post-doctoral research grant  ( H2020-MSCA-IF-2018 ,  DNANanoProbes 846571 ) by the  European Union.
Methods Molecular Dynamics simulations. All simulations are carried out using LAMMPS simulation package  48  (stable release 7 Aug 2019). Electrostatic interactions are calculated using the PPPM method with an accuracy of at least 10 -4 and a real-space cut-off r c = 12. 5 Å. Periodic boundary conditions are used in all dimensions with the non-electrostatic interactions being cut and shifted to zero at r c. For the simulations of the TF fluid and the salt in contact with an insulating/vacuum interface, the interactions between periodic images are not screened so that we employ the slab correction method proposed by Yeh and Berkowitz  49  with a vacuum layer of three times the simulation cell height. The non-electrostatic part of the salt-salt interactions are described using the Born-Meyer-Huggins potential which accurately reproduces the properties of NaCl (either as a crystal or molten salt), 41 U BMH (r) = A exp σ -r B - C r 6 - D r 8 , (7) The corresponding force field parameters are given in Supplementary Table  1.
Acknowledgements We acknowledge  V. Kaiser  for his help with the  Thomas-Fermi model and computation time through CIMENT infrastructure (Rhône-Alpes   CPER07 13 CIRA ) and Equip@ Meso  project ( ANR-10-EQPX-29-01 ). We also acknowledge funding from the  ANR  project  TAMTAM  ( ANR-15-CE08-0008-01 ). AS acknowledges funding from the  DFG  under Germany's Excellence Strategy -EXC  2075 -390740016  and  SFB 1313  (Project Number  327154368 ) and support by the  Stuttgart Center for Simulation Science (SimTech).
Acknowledgements Business Finland is gratefully acknowledged for financial support (project # 2291/31/2017 ). The authors thank the  SYSPROD  project and  AXELERA Pôle de Compétitivité  for financial support (PSMN Data Center). This work was granted access to the HPC resources of CINES, IDRIS, and  TGCC  under the allocation 2018-080609 made by  GENCI. The authors acknowledge the  French agency ANR  ( TeneMod  project  ANR-17-CE29-0007-21 ) for financial support. The authors gratefully acknowledge the support of the  Centre Blaise Pascal 's IT test platform at  ENS de Lyon (Lyon, France)  for its facilities. The platform operates the SIDUS solution developed by  Emmanuel Quemener. FAPESP-São Paulo Research Foundation ,  Brazil  (project # 2018/05280-5 ) and  CNPEM  for providing the beamtime at the TGM beamline of LNLS (# 20180001 ) are acknowledged.
For example, vapor-liquid equilibrium (VLE) measurements for binary mixtures should be normally accompanied by the pure-component vapor pressures measured with the same apparatus  [20] , and pure-component melting properties should be presented as part of binary SLE (solid-liquid equilibrium) phase diagrams. b) The reporting of high-pressure measurements (such as for density or speed of sound) should also include measurements from low-pressure regions when feasible. c) Related properties necessary for analyzing the main data should be measured, if possible (e. g. , melting temperatures and enthalpies of fusion to complement solid solubility data). Measuring over a range of conditions (temperature, etc. ) is more valuable than measuring for a single point. If the range is limited by special points (for example, liquid-liquid equilibrium in a ternary system limited by an isothermal critical-mixing-point, i.
In this context, the absence of the direct link between the chemical space of the generated fragments and the pool of available BBs makes tools like RECAP and BRICS appear as rather theoretical, reality-disconnected approaches, distant from down-to-earth practical library design based on the reagents present in the laboratory drawers. 18 me methodologies of library de-novo designs considering BBs availability have been previously reported, including both commercial/proprietary software  [19] [20] [21]  and methodologies used mostly by the authoring academic group  22   The label is associated with those reagent classes that can produce a given synthon (see Table  1 ). In total, there are almost 150 mono-bi-and tri-functional subclasses. The chemical validity of a synthon allows users to treat it as any other chemical structures: to assess different properties using machine-learning models, to evaluate similarity, and to visualize their chemical space.
General description of SynthI SynthI is a python3 RDkit-based  9  (v. 2021. 03. 1) library that generates synthons from larger molecules via fragmentation or from small reagents via functional group transformations. Being a knowledge-based tool, SynthI is based on the extensive library of SMARTS, defining each reagent class and SMIRKS that specify the reaction rules for synthon generation from BBs, pseudoretrosynthetic bond disconnections, or synthon recombination. SynthI consists of four modules (Figure  1 ), each being responsible for a particular task. In the following chapters, you can find a detailed description of each of them.
In addition, there are 28 bifunctional and 19 trifunctional classes. In the first version of SynthI, there will be no heterocyclization reactions. From the library design point of view, their usage would lead to the destruction of the privileged scaffolds that contribute significantly to the exhibited activity. Therefore, in the first implementation of SynthI heterocyclization reactions were not taken into consideration. For more detailed retrosynthesis, however, those reactions are highly important, therefore we are currently working on the implementation of the SynthI-Heterocyclization module that would allow the user to select whether they want to include cycle bonds disconnection.
SynthI-BBs The same BB can be assigned to several classes followed by the generation of synthons, corresponding to each class using SynthI-BBs module. In each synthon, the special labels are placed at the former position of the leaving groups (Figure  2  and Table  1 ). They define the type of the bond disconnection and reaction center (RC) -electrophile, nucleophile, radical, etc. The full list of unique synthons generated from the user-provided BBs library produces a chemical space of available synthons. In the case of a compound containing protective groups, it is up to the user to decide whether to keep protected synthons or not (keepPG option). The list of more than 400 synthons types that can be generated from all BB classes is provided in SynthI_BB_classes_and_respectiveSynthons. xls available on GitHub.
Scheme 2. Example of RECAP disconnection of the bond that can be formed via different reactions. The reaction rules behind SynthI were collected based on the analysis of current literature and our experience in medicinal chemistry synthesis. It included various reactions, leading to: • several ways of disconnection of the same strategic bonds that were already considered in RECAP and/or BRICS (Buchwald-Hartwig amination  26  , Cu-mediated C-N/O coupling  27  , umpolung cross-coupling  28  , Chan-Evans-Lam coupling  29  , olefin metathesis  30  , non-classical carbonyl olefination (like Julia-Kocienski)  [31] [32]  , C-H activation  33  , sulfonyl fluorides chemistry  34  , Suzuki CAr-CAr cross-coupling, novel methods for CAr-Csp3 couplings). • disconnection of the new strategic bonds absent in the previous implementation (Heck CAr-Csp2, Sonogashira CAr-Csp and Suzuki Csp2-Csp2 couplings, imines, oximes, hydrazones, and semicarbazones synthesis, sulphinic acid salts alkylation and their Cu-catalyzed arylation) Also, the set of new radical chemistry, as well as new methods of late-stage functionalization (Baran diversinates  35  , Minisci-type reaction  36  ), were included in SynthI.
These new reactions and the new more effective conditions for them  37  have changed dramatically the modern retrosynthetic thinking of the medicinal chemist  14, 38. In total, SynthI contains 13 broad reaction types for the bond disconnections and 37 subtypes, that may lead to different synthons. For example, for the "Olefination" type, there are two subtypes -"Knoevenagel-, Wittig-, Julia-Kocienski-type reactions" and "Olefin Metathesis". The first one is the example of polar bond disconnection resulting in bivalent electrophilic and nucleophilic synthons, while the second one produces neutral biradicals (Scheme 3). Obtained synthons can be traced back to the potential BBs for compound synthesis. The full list of reaction rules with some examples is available in the Supporting Information.
Using synthons as a unified representation, SynthI allows merging the chemical space of BBs (or rather structural increments that they bring to the final molecule) with a chemical space of fragments, obtained via pseudo-retrosynthetic bond disconnections. The herein-developed system of labels encodes the position and chemical nature of the reactive centers while preserving structure validity, allowing to treat synthons as actual compounds. In our approach, synthons are not fragments with open valences complemented by dummy atoms like in AllChem  23  or Ftrees-FS  40  that can be processed only by the parent software, but valid molecules in which marked atoms specify their anchoring points. Such representation allows, unlike in other approaches, processing of synthons structures by various chemoinformatic tools.
Data And Software Availability As a source of available BBs, the library of 201 675 in-stock reagents provided by Enamine was used. Seventy-nine drugs, recently approved by FDA, have been used as a dataset for fragmentation and analogs generation. The full list, together with fragmentation results, can be found in Supporting Information. The code of SynthI is publicly available at https://github. com/Laboratoire-de-Chemoinformatique/SynthI. ABBREVIATIONS SynthI, Synthons Interpreter; BBs, building blocks (here -synonym for reagents); PAS, position analogs scanning; RC, reaction center.
Here we describe a new open-source toolkit for synthons-based de novo library design, called Synthons Interpreter (SynthI), available at https://github. com/Laboratoire-de- Chemoinformatique/SynthI. In chemoinformatics, synthons were first introduced by R. D. Cramer et al. 23in 2007 as structures with one or more open valences, each having a defined reactivity. In this work, synthons are defined differently: the open valence at the connection/disconnection point is complemented by hydrogen atom(s) and a special label determining its reactivity is assigned.
ACKNOWLEDGMENTS MHR acknowledges financial support by the Agence Nationale pour la Recherche through the project BIO-MAGNET (ANR-16CE29-0008-01). Centre de Calcul Intensif d'Aix-Marseille is acknowledged for granting access to its high performance computing resources. MAR and CdG acknowledge the Spanish ministry of Science and Innovation (Project PID2020-113187GB-I00) and the Genralitat de Catalunya (project 2017-SGR629) for financial support.
However, other major factors combined to make this happen: the fast development of efficient molecular orbital (MO)-based software (the GAUSSIAN suit of programs  [66]  and others), the synthesis of aromatic and antiaromatic molecules (a dichotomy that initially evaded VB theory), and the formulation of attractive qualitative concepts, like Walsh diagrams, Fukui's frontier molecular orbital theory, the Woodward-Hoffmann rules of conservation of orbital symmetry  [67] , and the synthesis of molecules like ferrocene and the elegant interpretation of its unusual bonding by MO theory  [59]. The fact that MOT described excited states pictorially and simply, with excitations from bonding to antibonding MOs made it attractive to spectroscopists. Finally, the entrance of density functional theory into chemistry and its formulation in terms of Kohn-Sham MOs  [68] , which looked like simple Extended Hückel MOs, thus developing the same MO interaction diagram types [69], which made MO theory attractive to chemists  [67].
Sometime later, Gerratt, Raimondi and Cooper developed a related VB method called the spin coupled (SC) theory, now called "SCGVB", which also uses atomic orbitals (AOs) with delocalization tails. This is followed up by configuration interaction using the SCVB method  [98] [99] [100]. These methods are now incorporated in the MOLPRO software. GVB and SCGVB theories do not employ covalent and ionic structures explicitly. Nevertheless, the delocalization tails of these AOs effectively incorporate all the ionic structures  [22]  (pp. [40] [41] ) and thereby enable one to express the electronic structures in compact forms based on formally covalent pairing schemes. Balint-Kurti and Karplus  [101]  developed a multi-structure VB method that may utilize explicitly covalent and ionic structures with local atomic orbitals.
In a later development by van Lenthe and Balint-Kurti  [102, 103]  and by Verbeek and van Lenthe  [104, 105] , the multi-structure method is referred to as a VB self-consistent field (VBSCF) method. In a subsequent development, van Lenthe, Verbeek and co-workers generated the multipurpose VB program called TURTLE  [106, 107] , which has been incorporated into the MO-based package of programs GAMESS-UK. Matsen  [108, 109] , McWeeny  [110] , and Zhang and co-workers  [111, 112]  developed spin-free VB approaches based on symmetric group methods. Subsequently, Wu et al. extended the spin-free approach, and produced a general-purpose VB program initially called the XIAMEN-99 package, and more recently named XMVB  [113, 114]. XMVB is becoming faster and more efficient every year, and its VBSCF routine can include up to 26 orbitals/26 electrons in the VB space  [97, 115] , and can also handle molecules with two transition metals and as many as 10 ligands like CO  [116].
The new XMVB versions also have DFVB methods, which combine DFT and VBT  [117]. Soon after the XIAMEN-99 package, Li and McWeeny announced their VB2000 software, which is also a general-purpose program, including a variety of methods  [118]. Another software of multiconfigurational VB (MCVB), called CRUNCH and based on the symmetric group methods of Young was written by Gallup and co-workers  [119, 120]. During the early 1990s, Hiberty and co-workers developed the breathing orbital VB (BOVB) method, which also utilizes covalent and ionic structures, but in addition, allows them to have their own unique set of orbitals  [121] [122] [123] [124] [125]. In this manner, BOVB introduces dynamic correlation to bonding and improves the quantitative results vis à vis VBSCF. The method is now incorporated into the TURTLE and XMVB packages.
XMVB is versatile. Thus, Wu et al. [126] developed a VBCI method, which is akin to BOVB, but can be applied to larger systems, since the method starts from VBSCF and improves the orbitals by excitation to virtual orbitals without changing the number of VB structures. In a more recent work, the same authors coupled VB theory with the solvent model, PCM, and produced the VBPCM program that enables one to study reactions in solution  [127]. More recent developments involve coupling simple VBSCF calculations (which are fast) with Monte Carlo Simulations to retrieve missing correlation effects  [128]. These VB-Monte Carlo methods project a fruitful future direction for VBT. Finally, Truhlar and co-workers  [129]  developed the VB-based multiconfiguration molecular mechanics method (MCMM) to treat dynamic aspects of chemical reactions, while Landis and co-workers  [130]  introduced the VAL-BOND method that is capable of predicting structures of transition metal complexes using Pauling's ideas of orbital hybridization.
Determination of Minimum Inhibitory Concentrations In order to compare the antimicrobial activity of limonene, RuL3, and the microencapsulated RuL3, their minimum inhibitory concentrations were measured against Escherichia coli. Staphylococcus aureus, Listeria monocytogenes, and Enterococcus faecalis (Table  1 ). DMSO (2%) used to enhance the water miscibility of limonene, did not affect the growth of the considered strains at this DMSO concentration (data not shown). The MIC values for limonene against all considered strains were 12. 5 mg/ml. Compared with limonene, the MICs (0. 4 mg/ml) of the RuL3 complex was approximately 30-fold lower. Thus, the complexation of limonene with 233 Ruthenium enhanced its antibacterial potential. In addition, Table  1  shows that the MIC values of microencapsulated RuL3 were fourfold lower against all studied strains than those of free RuL3.
Impact of Free and Microencapsulated RuL3 Treatment on E. coli Morphology Escherichia coli was used in order to measure the effect of free and microencapsulated RuL3 treatments on the bacterial cells. The bacterial cells were exposed to the MIC values of free and microencapsulated RuL3. The structural morphology of the treated E. coli was observed by SEM (Figure  4 ). Figure  4  shows that untreated cells (control) had a regular and normal bacilliform structure. However, the micrographs of the cells treated with free and microencapsulated RuL3 shows different forms of distortion and deformation (Figure  4 ). Furthermore, treated cells endured a complete collapse of the morphology of the cells accompanied by intercellular pool leakage (Figure  4 ). Similar results were obtained with Staphylococcus aureus (data not shown).
After 10 min, the GFP fluorescence intensity increased by 1. 5-fold in the supernatant filtrates of the bacterial suspension treated with DTAC. However, no fluorescence increase was measured after the addition of the free microencapsulated RUL3. These results were in agreement with these obtained by an analysis, using SDS page electrophoresis, of intracellular proteins in the supernatant before and after the addition of the free or microencapsulated RUL3 (data not shown). These results show that the free or microencapsulated RUL3 induce potassium release but not protein leakage from the cytoplasm.
Angiogenic Array Angiogenic arrays (human angiogenesis antibody array-membrane; Abcam Cambridge UK) were employed for the simultaneous detection of 43 growth factors and cytokines in DPSCs cultured in 2D and 3D. The assay procedure was performed as described in the manufacturer's instructions, using 14 day conditioned medium from DPSCs cultured in either 0. 5% w/v NapFFεKεK-OH hydrogels or standard 2D culture. Arrays were imaged using a Syngene G: BOX, with GeneSys software and semiquantified using ImageJ, image analysis programme, with a microarray plugin. Results were presented as a heat map generated using Microsoft Excel.
Statistical Analysis Results were expressed as the mean of three independent experiments with three to six replicates per experiment. GraphPad Prism Software (Version 8) was used to perform statistical analysis (GraphPad Software Inc. , San Diego, CA, USA). MTT assay results were analysed by one-way ANOVA followed by Dunnett's post hoc multiple comparison test. Comparisons were made with HPMC controls in the modified MTT assay. Biofilm inhibition and bacterial viability results were analysed by Mann-Whitney non parametric tests, and comparisons were made with untreated controls or vehicle control treatments respectively. The level of statistical significance was set at p < 0. 05.
Angiogenic Array Angiogenic arrays (human angiogenesis antibody array-membrane; Abcam Cambridge UK) were employed for the simultaneous detection of 43 growth factors and cytokines in DPSCs cultured in 2D and 3D. The assay procedure was performed as described in the manufacturer's instructions, using 14 day conditioned medium from DPSCs cultured in either 0. 5% w/v NapFFεKεK-OH hydrogels or standard 2D culture. Arrays were imaged using a Syngene G: BOX, with GeneSys software and semiquantified using Im-ageJ, image analysis programme, with a microarray plugin. Results were presented as a heat map generated using Microsoft Excel.
All comparisons were made with untreated controls. Mann-Whitney non parametric testing was employed for statistical analysis. ns: no significant difference (p > 0. 05), **: p ≤ 0. 01. (PLGF), regulated upon activation normal T cell expressed and secreted (RANTES), tissue inhibitor of matrix metalloproteinases (TIMP)-1, TIMP-2, angiopoietin-1 (ANGPT1), angiopoietin-2 (ANGPT2), T lymphocyte-secreted protein I-309 (I-309), IL-10, IL-1α, IL-1β, IL-2, IL-4, interferon-inducible T cell alpha chemoattractant (I-TAC), monocyte chemoattractant protein (MCP)-3, MCP-4, MMP (matrix metalloproteinase)-1, MMP-9, tyrosine kinase with immunoglobulin-like and EGF-like domains (TIE-2) and tumour necrosis factor alpha (TNFα) (Figure  6 ). The heat map was generated in Excel using a 3-colour scale whereby red colour represents no expression above baseline, yellow represents the median expression level of the dataset and green represents the 90% percentile of the expression levels obtained.
Computational approach To understand the formation mechanism and structure of the observed fragments, theoretical simulations were carried out on the three smallest fragment ions. As previously,  [43] [44] [45] [46]  simulations were performed using the genetic algorithm tool Fafoom  47, 48  to enable effective characterization of the potential energy surface. The structures were optimized using the MMFF94 force field. [49] [50] [51] [52] [53]  This approach samples a wide range of ring structures incorporating multiple chair, boat, and skew forms, enabling a thorough interrogation of the potential energy surface. All oxygen sites had sodium cations added using custom scripts to generate starting points for the calculations. Geometry optimizations of the resulting candidate conformations were performed with the Gaussian 09 software package  54  at the HF/3-21G, B3LYP/6-31G(d), and B3LYP/ 6-31+G(d,p) levels of theory.
Acknowledgements E. C. , R. P. P. , A. B. K. , and T. R. R. thank the  Swiss National Science Foundation  (Grant  200020_184838 ), the  European Research Council  (Grant  788697-GLYCANAL ), and the  EPFL  for the financial support of this work. J. M. R. and B. J. B. were supported by the  National Science Foundation  under  CHE-1948611  and  ACI-1919789 ,  Ohio University , and performed some calculations at the  Ohio Supercomputer Center  (http:// osc. edu/ark:/19495/f5s1ph73).
, 2018). The investigations of the interactions in heterogeneous phase (gas/ condensed phases) in a TGT have been initiated in 1990s at the United Kingdom Atomic Energy Authority  (Bowsher et al, 1985 (Bowsher et al, , 1986)). Authors observed that boric acid can react with a part of caesium iodide, leading to the release of gaseous iodine. In the framework of the WIND (Wide Range Piping Integrity Demonstration) project at the Japan Atomic Energy Research Institute (JAERI)  (Shibazaki et al. , 2000) , reactivity between caesium iodide particles deposited onto the surfaces of a TGT (1270 K-640 K) and a metaboric acid layer placed beforehand, was noticed. Deposited caesium iodide was mostly decomposed at the temperature exceeding approximately 770 K. The past work brought a lot of information on the reactions between caesium iodide and boric acid in a TGT, broadening the database in several conditions and demonstrating how presence of boric acid can affect the physical and chemical forms of iodine and caesium, in particular through the formation of stable condensed caesium borates (Cs x B y O z )  (Vandeputte et al.