Alkyl Functional Groups Research Articles

Unraveling Chain Branching in Cool Flames.

In cool flames, autoxidation of organic compounds forms alkyl hydroperoxides and ketohydroperoxides, and this controls the critical rate of chain branching, but there have been large uncertainties in the decomposition rate constants. We synthesized a series of hydroperoxides and measured their decomposition rate constants in pyrolysis experiments by spray-vaporization jet-stirred-reactor synchrotron vacuum ultraviolet photoionization mass spectrometry. Structural variation of the hydroperoxides, including alkyl, cycloalkyl, aromatic, and heterocyclic functionalities, has only a slight effect on their decomposition rate constants. Calculated rate constants are in good agreement with the experiment. The rate constant of ketohydroperoxide decomposition was obtained by theoretical calculation of 3-hydroperoxy butanal and tested by the pyrolysis of synthesized 3-hydroperoxy-3-phenylpropionate. The rate constant of ketohydroperoxide decomposition is close to that of alkyl hydroperoxides. The new chain-branching rate constants improves the cool-flame kinetic model, which is essential for removing discrepancies in model predictions and for the design of high-efficiency and low-emission engines.

Rhodium-Catalyzed Pyridylation of Alkynamides with Pyridylboronic Acids: A Route to Functionalized Enamides.

The catalytic direct hydroarylation of alkynamides is a highly efficient approach for accessing functionalized trisubstituted arylalkenes with amide groups. Herein, we report a rhodium-catalyzed pyridylation of alkynamides with pyridylboronic acids, producing a variety of primary, secondary, and tertiary enamides with high yields (up to 94 %). This reaction demonstrates broad tolerance towards various alkyl and aryl functional groups, providing convenient access to a diverse array of alkenylpyridine derivatives. To demonstrate potential applications in late-stage hydropyridylation, we synthesized α,β-unsaturated ketones, aldehydes, and esters with high yields from the pyridylation product of Weinreb amides. This indirect expansion of the substrate scope enhances the practicality of this strategy. Additionally, the α,β-unsaturated ketone obtained can be further reduced to yield a chiral alcohol with a 99 % ee, further demonstrating the versatility and potential utility of this approach.

Manganese-Catalyzed Synthesis of Polyketones Using Hydrogen-Borrowing Approach.

We report here a method of making polyketones from the coupling of diketones and diols using a manganese pincer complex. The methodology allows us to access various polyketones (polyarylalkylketone) containing aryl, alkyl, and ether functionalities, bridging the gap between the two classes of commercially available polyketones: aliphatic polyketones and polyaryletherketones. Using this methodology, 12 polyketones have been synthesized and characterized using various analytical techniques to understand their chemical, physical, morphological, and mechanical properties. Based on previous reports and our studies, we suggest that the polymerization occurs via a hydrogen-borrowing mechanism that involves the dehydrogenation of diols to dialdehyde followed by aldol condensation of dialdehyde with diketones to form chalcone derivatives and their subsequent hydrogenation to form polyarylalkylketones.

A Radical Activation Strategy for Versatile and Stereoselective N‐Glycosylation

AbstractPrevious N‐glycosylation approaches have predominately involved acidic conditions, facing challenges of low stereoselectivity and limited scope. Herein, we introduce a radical activation strategy that enables versatile and stereoselective N‐glycosylation using readily accessible glycosyl sulfinate donors under basic conditions and exhibits exceptional tolerance towards various N‐aglycones containing alkyl, aryl, heteroaryl and nucleobase functionalities. Preliminary mechanistic studies indicate a pivotal role of iodide, which orchestrates the formation of a glycosyl radical from the glycosyl sulfinate and subsequent generation of the key intermediate, a configurationally well‐defined glycosyl iodide, which is subsequently attacked by an N‐aglycone in a stereospecific SN2 manner to give the desired N‐glycosides. An alternative route involving the coupling of a glycosyl radical and a nitrogen‐centered radical is also proposed, affording the exclusive 1,2‐trans product. This novel approach promises to broaden the synthetic landscape of N‐glycosides, offering a powerful tool for the construction of complex glycosidic structures under mild conditions.

A Radical Activation Strategy for Versatile and Stereoselective N-Glycosylation.

Previous N-glycosylation approaches have predominately involved acidic conditions, facing challenges of low stereoselectivity and limited scope. Herein, we introduce a radical activation strategy that enables versatile and stereoselective N-glycosylation using readily accessible glycosyl sulfinate donors under basic conditions and exhibits exceptional tolerance towards various N-aglycones containing alkyl, aryl, heteroaryl and nucleobase functionalities. Preliminary mechanistic studies indicate a pivotal role of iodide, which orchestrates the formation of a glycosyl radical from the glycosyl sulfinate and subsequent generation of the key intermediate, a configurationally well-defined glycosyl iodide, which is subsequently attacked by an N-aglycone in a stereospecific SN2 manner to give the desired N-glycosides. An alternative route involving the coupling of a glycosyl radical and a nitrogen-centered radical is also proposed, affording the exclusive 1,2-trans product. This novel approach promises to broaden the synthetic landscape of N-glycosides, offering a powerful tool for the construction of complex glycosidic structures under mild conditions.

Boosting dynamic fluorescent materials using SP@Tb-MOFs through the alkyl functionalization of pores and applications in time-dependent information encryption

Boosting dynamic fluorescent materials using SP@Tb-MOFs through the alkyl functionalization of pores and applications in time-dependent information encryption

Synthesis of Metastable Calcium Carbonate Using Long-Chain Bisphosphonate Molecules.

Cementation in construction materials primarily relies on the aqueous precipitation of minerals such as carbonates and silicates. The kinetics of nucleation and growth play a critical role in the development of strength and durability, yet our understanding of the kinetic controls governing phase formation and porosity reduction in cements remains limited. In this study, we synthesized bisphosphonate molecules with varying alkyl chain lengths and functional groups to investigate their impact on calcium carbonate precipitation. Through conductivity measurements, infrared spectroscopy, and thermogravimetric analysis, we uncovered the selective formation of polymorphs and the specific incorporation of these molecules within the carbonate matrix. Further, in situ atomic force microscopy revealed that these molecules influenced the morphology of the precipitates, indicating a possible effect on the ionic organization through sorption mechanisms. Interestingly, amorphous calcium carbonate (ACC), when formed in the presence of bisphosphonates, showed metastability for at least seven months without inhibiting further calcium carbonate precipitation. Our research sheds light on the diverse mechanisms by which organic additives can modify mineral nucleation and growth, offering valuable insights for the control and enhancement of carbonate-based cementation processes.

Synergistic effects of mechanochemical activation and selective O-alkylation on the chemical structure and gaseous products evolution during coal flash pyrolysis

Mechanochemical activation offers significant advantages in enhancing the pore structure and active sites of materials, while selective O-alkylation boosts both the homogeneous and heterogeneous reactivity of coal. In this work, mechanochemical activation and selective O-alkylation are synergistically applied to modify pulverized coal. The evolution of the chemical structure was thoroughly characterized using ultimate analysis, Fourier-transform infrared spectroscopy (FTIR), and nuclear magnetic resonance (NMR). Pyrolysis gas chromatography-mass spectrometry (PY-GC-MS) was utilized to investigate the release of crucial gaseous products during the pyrolysis. Additionally, this study focuses on the synergistic effects of mechanochemistry and selective O-alkylation on the chemical structure and pyrolysis characteristics. The results reveal that alkylation boosts the formation of C-O bonds and aliphatic carbon while reducing the presence of aromatic carbon. Moreover, by disrupting intermolecular forces, alkylation induces the fragmentation of expansive aromatic layers into smaller aromatic fragments, thereby generating additional structural defects. Furthermore, the electron transfer process facilitates the conversion of aromatic carbon into aliphatic forms through ring-opening reactions. On the other hand, incorporating alkyl functional groups and initiating ring-opening reactions of aromatic carbons lead to a rise in aliphatic hydrocarbons during the pyrolysis of alkylated coal. However, intensified mechanochemical action hinders the production of aliphatic hydrocarbons. Additionally, during alkylation, the creation of esters and ethers with elevated thermal stability delays the release of oxygen-containing gas products. The findings propose a new pretreatment method for coal utilization, promoting the development of new low-NOx combustion technology.

Alkyl-terminated PEG suppressors for copper electroplating and their hydrophilic and hydrophobic properties

This study explores the structure-activity relationship of copper electroplating suppressors, with a focus on alkyl-terminated polyethylene glycols (PEGs), to better understand their efficacy in electronic interconnect fabrication. Electrochemical analysis demonstrated that an increase in the molecular weight of PEG suppressors significantly raises the electrochemical polarization overpotential during copper electrodeposition. Additionally, alkyl terminal capping was observed to amplify this polarization effect, with the extent of overpotential increase directly correlating with the alkyl chain length. However, the advantageous impact of molecular weight on overpotential diminishes at higher molecular weights. In contrast to the electrochemical results, through-hole electroplating experiments revealed that a suppressor with a molecular weight of 1 k and butyl termination exhibits superior through-hole throwing power. Further analysis indicated that a greater proportion of alkyl functional groups within the suppressor's molecular chain enhances uniform electroplating capabilities. The study also suggests that measuring contact angles, as an expression of hydrophobicity, could provide a more efficient and precise method for evaluating suppressor performance.

Small-Angle X-ray Scattering Study of the Amphiphilic Bulk Nanostructure of Tetraalkylammonium Deep Eutectic Solvents.

Deep eutectic solvents (DESs) are low-melting mixtures, often prepared from a salt and a molecular hydrogen bond donor. Like ionic liquids, DESs that contain at least one sufficiently amphiphilic component can form bicontinuous nanostructures consisting of polar and nonpolar domains, although this has not been widely explored for many DES combinations. Here, the bulk nanostructures of DESs comprising tetraalkylammonium bromide salts (tetrabutylammonium bromide, tetraoctylammonium bromide, and methyltrioctylammonium bromide) with alkanols and alkanoic acids of systematically varied chain lengths (C2, C6, C8, and C10) as hydrogen bond donors have been studied. Small-angle X-ray scattering techniques were used to identify the relationship between the alkyl chain length and functionality of the hydrogen bond donor on the nature of the amphiphilic nanostructures formed. These findings demonstrated that the amphiphilic nanostructures of the DESs were not affected by the functional group on the hydrogen bond donor, with these nanostructures influenced primarily by both the absolute and relative alkyl chain lengths of the salt and hydrogen bond donor.

Physicochemical Analysis of Biofilms from Cocos nucifera Linn. (Coconut) Flour and Manihot esculenta Crantz (Cassava) Starch with Polyvinyl Alcohol (PVA)

The province of Northern Samar, its municipalities including Pambujan, is a place abundant of Manihot esculenta Crantz (cassava), and Cocos nucifera Linn. (coconut). However, its industry is mainly limited to food production. This study developed biofilms from cassava starch (CasS), and coconut flour (CoF) with polyvinyl alcohol (PVA). The physicochemical properties were analyzed to determine their pH, solubility, moisture content, and tensile strength. Functional groups were investigated using FTIR, and the antibacterial properties were evaluated. The results showed that both biofilms with PVA were weakly acidic and insoluble in all solvents. Meanwhile, CoF biofilm contained higher moisture content than the CasS biofilm. CoF biofilms also carried more weight and higher force than CasS biofilm. Hydroxyl, alkyl, and alkene functional groups were identified for both biofilms. Meanwhile, both biofilms showed no inhibitory effect against E. coli, and S. aureus. Therefore, the developed biofilms with PVA showed good physicochemical properties and can be used for packaging applications. The slight acidity can prolong their shelf-life. Moreover, both will not easily dissolve. CoF biofilm comprised more water than CasS but both are still suitable for packaging due to their tensile strength attributed to the presence of the functional groups. However, CasS, CoF, and PVA do not have antibacterial properties. More physicochemical tests, further characterization, and incorporation of antibacterial agents were recommended.

Electrochemical Capacitance Traces with Interlayer Spacing in Two‐dimensional Conductive Metal–Organic Frameworks

AbstractElectrically conductive metal–organic frameworks (MOFs) are promising candidates for electrochemical capacitors (EC) for fast energy storage due to their high specific surface areas and potential for redox activity. To maximize energy density, traditional inorganic pseudocapacitors have utilized faradaic processes in addition to double‐layer capacitance. Although conductive MOFs are usually comprised of redox active ligands which allow faradaic reactions upon electrochemical polarization, systematic studies providing deeper understanding of the charge storage processes and structure‐function relationships have been scarce. Here, we investigate the charge storage mechanisms of a series of triazatruxene‐based 2D layered conductive MOFs with variable alkyl functional groups, Ni3(HIR3‐TAT)2 (TAT=triazatruxene; R=H, Et, n‐Bu, n‐Pent). Functionalization of the triazatruxene core allows for systematic variation of structural parameters while maintaining in‐plane conjugation between ligands and metals. Specifically, R groups modulate interlayer spacing, which in turn shifts the charge storage mechanism from double‐layer capacitance towards pseudocapacitance, leading to an increase in molar specific capacitance from Ni3(HIH3‐TAT)2 to Ni3(HIBu3‐TAT)2. Partial exfoliation of Ni3(HIBu3‐TAT)2 renders redox active ligand moieties more accessible, and thus increases the dominance of faradaic processes. Our strategy of controlling charge storage mechanism through tuning the accessibility of redox‐active sites may motivate further design and engineering of electrode materials for EC.

Electrochemical Capacitance Traces with Interlayer Spacing in Two-dimensional Conductive Metal-Organic Frameworks.

Electrically conductive metal-organic frameworks (MOFs) are promising candidates for electrochemical capacitors (EC) for fast energy storage due to their high specific surface areas and potential for redox activity. To maximize energy density, traditional inorganic pseudocapacitors have utilized faradaic processes in addition to double-layer capacitance. Although conductive MOFs are usually comprised of redox active ligands which allow faradaic reactions upon electrochemical polarization, systematic studies providing deeper understanding of the charge storage processes and structure-function relationships have been scarce. Here, we investigate the charge storage mechanisms of a series of triazatruxene-based 2D layered conductive MOFs with variable alkyl functional groups, Ni3(HIR3-TAT)2 (TAT=triazatruxene; R=H, Et, n-Bu, n-Pent). Functionalization of the triazatruxene core allows for systematic variation of structural parameters while maintaining in-plane conjugation between ligands and metals. Specifically, R groups modulate interlayer spacing, which in turn shifts the charge storage mechanism from double-layer capacitance towards pseudocapacitance, leading to an increase in molar specific capacitance from Ni3(HIH3-TAT)2 to Ni3(HIBu3-TAT)2. Partial exfoliation of Ni3(HIBu3-TAT)2 renders redox active ligand moieties more accessible, and thus increases the dominance of faradaic processes. Our strategy of controlling charge storage mechanism through tuning the accessibility of redox-active sites may motivate further design and engineering of electrode materials for EC.

Modification of gelcoat based unsaturated polyester resin with functionalized octaspherosilicates to reduce the ice adhesion strength

Many composite structures used in various industries, such as wind turbines, aircraft, watercraft, lifeboats and others face the problem of ice build-up in winter seasons. The mechanical, thermal and chemical methods used so far to remove ice are inefficient, uneconomical and hurt the environment. Recently, surfaces have begun to be designed to eliminate or minimize ice accumulation, namely icephobic surfaces. The key parameter of such surfaces is the lowest possible ice adhesion strength (IA). One of the mechanisms for designing icephobic surfaces is a modification with compounds that direct hydrophobic properties. In this work, unsaturated polyester resin gelcoats modified with compounds from the group of octaspherosilicates with alkyl and methacrylic functional groups proposed as fluorine-free additives were investigated in terms of water repellent and ice adhesion. The surface roughness of the tested materials was measured. The surface zeta potential was also determined, which is new compared to available studies of surfaces for icephobic applications. The work also presents microstructure observations of the surface. Almost all of the modifiers increased the water contact angle (WCA), modifying the reference material from hydrophilic to slightly hydrophobic. The highest WCA was equal to 94°. The most important IA parameter was decreased by 56% compared to the unmodified gelcoat, with a value of 152 kPa. In addition, the study observed that the lowest value of IA correlated with the lowest value of CAH. The highest reduction in CAH was 44% compared to the reference sample. The roughness, wettability and IA parameters were determined before and after UV exposure to investigate modified gelcoats durability.

Reactive mesoporous organosoluble multifunctional hyperbranched polymer nanoparticles: Synthesis, post-polymerization reactions and clickable layer-by-layer coating

Synthesis of reactive organosoluble porous polymers, which can be useful for covalent layer-by-layer coatings, is synthetically challenging and not well known. In this work, we demonstrated a new approach to synthesize indole-decorated mesoporous hyperbranched polymer nanoparticles, which can be easily post-modified via triazolinedione (TAD)-indole click reaction. Importantly, further crosslinking of the polymer nanoparticles in solution leads to formation of insoluble mesoporous polymers, where porosity and surface area of the hyperbranched polymer nanoparticles further improved by ∼40%. Consequently, the nanoparticles are useful in layer-by-layer porous coatings and post-surface modifications. While studying their water repellent properties it was noted that nanoparticles having higher surface area/porosity results better water repellent surface which can be further enhanced via suitable surface functionalization using different long chain alkyl functionalities.

Electrochemical Vicinal C-H Difunctionalization of Saturated Azaheterocycles.

A method to functionalize two vicinal C-H bonds of saturated azaheterocycles is described. The procedure involves subjecting the substrate to a mixture of hydrochloric acid, acetic acid, and acetic anhydride in an undivided electrochemical cell at a constant current, resulting in stereoselective conversion to the corresponding α-acetoxy-β-chloro derivative. The α-position can be readily substituted with a range of other groups, including alkyl, aryl, allyl, alkynyl, alkoxy, or azido functionalities. Furthermore, we demonstrate that the β-chloro position can be engaged in Suzuki cross-coupling. This protocol thus enables the rapid diversification of simple five-, six-, and seven-membered saturated azaheterocycles at two adjacent positions.

The Antifungal Activities of Silver Nano-Aggregates Biosynthesized from the Aqueous Extract and the Alkaline Aqueous Fraction of Rhazya stricta against Some Fusarium Species.

Rhazya stricta is a major medicinal species used in indigenous medicinal herbal medications in South Asia, the Middle East, Iran, and Iraq to treat a variety of ailments. The current study aimed to investigate the antifungal properties of biosynthesized silver nanoparticles (AgNPs) made from R. stricta aqueous extract and its alkaline aqueous fraction. Fourier transform infrared spectroscopy (FTIR), UV-vis spectrophotometry, dynamic light scattering (DLS), and transmitted electron microscopy (TEM) were used to characterize AgNPs. The produced extracts and AgNPs were tested for their antifungal efficacy against four Fusarium spp. All of the characterization experiments proved the biosynthesis of targeted AgNPs. FTIR showed a wide distribution of hydroxyl, amino, carboxyl, and alkyl functional groups among all preparations. The DLS results showed that the produced Aq-AgNPs and the Alk-AgNPs had an average size of 95.9 nm and 54.04 nm, respectively. On the other hand, TEM results showed that the Aq-AgNPs and Alk-AgNPs had average diameters ranging from 21 to 90 nm and 7.25 to 25.32 nm. Both AgNPs absorbed UV light on average at 405 nm and 415 nm, respectively. Regarding the fungicidal activity, the highest doses of Aq-extract and Aq-AgNPs inhibited the mycelial growth of F. incarnatum (19.8%, 87.5%), F. solani (28.1%, 72.3%), F. proliferatum (37.5%, 75%), and F. verticillioides (27.1%, 62.5%), respectively (p < 0.001). Interestingly, the Alk-fraction had stronger inhibition than the biosynthesized AgNPs, which resulted in complete inhibition at the doses of 10% and 20% (p < 0.001). Furthermore, microscopic analysis demonstrated that both AgNPs caused obvious morphological alterations in the treated organisms when compared to the control. In conclusion, R. stricta's Aq-extract, alkaline fraction, and their biosynthesized AgNPs show substantial antifungal efficacy against several Fusarium spp. It is the first study to highlight the prospective biological activities of R. stricta Aq-extract and its alkaline fraction against F. incarnatum, F. proliferatum, and F. verticillioides. In addition, it is the first opportunity to deeply investigate the ultrastructural changes induced in the Fusarium species treated with R. stricta crude Aq-extract and its biosynthesized AgNPs. More studies are required to investigate their biological effect against other Fusarium or fungal species.

Nanocluster Surface Microenvironment Modulates Electrocatalytic CO2 Reduction.

The catalytic activity and product selectivity of the electrochemical CO2 reduction reaction (eCO2RR) depend strongly on the local microenvironment of mass diffusion at the nanostructured catalyst and electrolyte interface. Achieving a molecular-level understanding of the electrocatalytic reaction requires the development of tunable metal-ligand interfacial structures with atomic precision, which is highly challenging. Here, the synthesis and molecular structure of a 25-atom silver nanocluster interfaced with an organic shell comprising 18 thiolate ligands are presented. The locally induced hydrophobicity by bulky alkyl functionality near the surface of the Ag25 cluster dramatically enhances the eCO2RR activity (CO Faradaic efficiency, FECO: 90.3%) with higher CO partial current density (jCO) in an H-cell compared to Ag25 cluster (FECO: 66.6%) with confined hydrophilicity, which modulates surface interactions with water and CO2. Remarkably, the hydrophobic Ag25 cluster exhibits jCO as high as -240mA cm-2 with FECO >90% at -3.4V cell potential in a gas-fed membrane electrode assembly device. Furthermore, this cluster demonstrates stable eCO2RR over 120h. Operando surface-enhanced infrared absorption spectroscopy and theoretical simulations reveal how the ligands alter the neighboring water structure and *CO intermediates, impacting the intrinsic eCO2RR activity, which provides atomistic mechanistic insights into the crucial role of confined hydrophobicity.

Using Metadynamics to Reveal Extractant Conformational Free Energy Landscapes.

Understanding the impact of extractant functionalization on metal-binding energetics in liquid-liquid extraction is essential to guide the development of better separation processes. Traditionally, computational extractant design uses electronic structure calculations on metal-ligand clusters to determine the metal-binding energy of the lowest energy state. Although highly accurate, this approach does not account for all of the relevant physics encountered under experimental conditions. Such methodologies often neglect entropic contributions such as temperature effects and ligand flexibility, in addition to approximating solvent-extractant interactions with implicit solvent models. In this study, we use classical molecular dynamics simulations with an advanced sampling method, metadynamics, to map out extractant molecule conformational free energies in the condensed phase. We generate the complete conformational landscape in solution for a family of bidentate malonamide-based extractants with different functionalizations of the headgroup and the side chains. In particular, we show how such alkyl functionalization reshapes the free energy landscape, affecting the free energy penalty of organizing the extractant into the cis-like metal-binding conformation from the trans-like conformation of the free extractant in solution. Specifically, functionalizing alkyl tails to the center of the headgroup has a greater influence on increasing molecular rigidity and disfavoring the binding conformation than functionalizing side chains. These findings are consistent with trends in metal-binding energetics based on experimentally reported distribution ratios. We also consider a different bidentate extractant molecule, carbamoylmethylphosphine oxide, and show how the choice of solvent can further reshape the conformational energetic landscape. This study demonstrates the feasibility of using molecular dynamics simulations with advanced sampling techniques to investigate extractant conformational energetics in solution, which, more broadly, will enable extractant design that accounts for entropic effects and explicit solvation.

Design and Synthesis of Novel 2-Acetamido, 6-Carboxamide Substituted Benzothiazoles as Potential BRAFV600E Inhibitors - In vitro Evaluation of their Antiproliferative Activity.

The oncogenic BRAFV600E kinase leads to abnormal activation of the MAPK signaling pathway and thus, uncontrolled cellular proliferation and cancer development. Based on our previous virtual screening studies which issued 2-acetamido-1,3 benzothiazole-6-carboxamide scaffold as active pharmacophore displaying selectivity against the mutated BRAF, eleven new substituted benzothiazole derivatives were designed and synthesized by coupling of 2-acetamidobenzo[d]thiazole-6-carboxylic acid with the appropriate amines in an effort to provide even more efficient inhibitors and tackle drug resistance often developed during cancer treatment. All derived compounds bore the benzothiazole scaffold substituted at position-2 by an acetamido moiety and at position-6 by a carboxamide functionality, the NH moiety of which was further linked through an alkylene linker to a sulfonamido (or amino) aryl (or alkyl) functionality or a phenylene linker to a sulfonamido aromatic (or non-aromatic) terminal pharmacophore in the order -C6 H4 -NHSO2 -R or reversely -C6 H4 -SO2 N(H)-R. These analogs were subsequently biologically evaluated as potential BRAFV600E inhibitors and antiproliferative agents in several colorectal cancer and melanoma cell lines. In all assays applied, one analog, namely 2-acetamido-N-[3-(pyridin-2-ylamino)propyl]benzo[d]thiazole-6-carboxamide (22), provided promising results in view of its use in drug development.