Bridgehead Carbon Research Articles

Design and Evaluation of Azaspirocycles as RNA binders.

This study presents efficient synthetic pathways for preparing novel azaspirocycles. These methodologies involve functionalizing key bicyclic hydrazines with a substituent on one of their bridgehead carbon atoms. The desired spirocyclic cores were successfully obtained through double reductive amination reactions, intramolecular cyclizations, and cleavages of the N-N bond. The isolated molecules possess unique three-dimensional structures, suggesting potential applications in medicinal chemistry and drug discovery. With the growing interest in targeting nucleic acids as a complementary approach to protein-targeting strategies for developing novel active compounds, we investigated the potential of the synthesized azaspirocycles as RNA binders. As a proof of concept, we highlight the promising activity of some compounds as strong binders of HIV-1 TAR RNA and inhibitors of Tat/TAR interactions.

Synthesis of π-Extended [1.1]Paracyclophanes, [1.1][n]PCP (n=2, 3, and 4), and Their Through-Space Conjugation.

[1.1][n]Paracyclophanes ([1.1][n]PCPs) (3) with n=2, 3, and 4, which consist of two [n]paraphenylene units connected by methylene bridges, were synthesized using short synthetic pathways with good overall yields. Single-crystal X-ray diffraction analyses reveal that the paraphenylene unit in 3 is bent, resulting in an elliptic core structure of 3. The facing bridgehead carbons of the paraphenylene units are separated by a distance much shorter than the sum of the van der Waals radii of sp2-carbon atoms. UV-vis absorption spectra, fluorescence spectra, electrochemical measurements, and theoretical calculations were used to demonstrate the presence of through-space (TS) conjugation in 3. Furthermore, host-guest complex formation between 3D (n=3) and tetracyanoquinodimethane in the solid state was revealed.

Polyprenylated Benzoylphloroglucinols Isolated from Garcinia Species and Their Cytotoxic Effects on Cancer Cell Lines.

Polyprenylated benzoylphloroglucinols (PPBPs) make up a group of complex natural products with anticancer potentials that are mainly distributed in Garcinia plants. As part of our intensive exploration on new bioactive substances from this genus, we report two undescribed PPBPs, picrorhizones I (1) and J (2), along with four known analogues (3-6) from the stem bark of Garcinia picrorhiza and Garcinia gracilis. The new structures were elucidated on the basis of spectroscopic analysis, particularly 1D and 2D NMR and HRESIMS, whereas the absolute configurations were determined by a combination of ECD and NMR calculations coupled with a DP4+ probability analysis. Being the least class in genus Garcinia, picrorhizone I possesses a type-A structure with the position of a benzoyl moiety attaching to one of the bridgehead carbons of a bicyclo[3.3.1]nonane skeleton, which differs from its major type-B counterparts. This work also represents the first report on the occurrence of PPBPs in G. gracilis. The cytotoxic evaluation of the isolated compounds revealed that isogarcinol (4) and garciyunnanin L (5) significantly inhibited the growth of KB and Hela S3 cancer cells with IC50 values lower than 10 μM, while 5 was also strongly active against the Hep G2 cancer cell line with an IC50 value of 8.02 μM. Among the B-class derivatives bearing a lavandulyl side chain, cyclization of the moiety in the bicyclic phloroglucinol skeleton enhanced the cytotoxic properties on cancer cells.

Pyrolysis characteristics and kinetic analysis of coating pitch derived from ethylene tar using model-free and model-fitting methods

This work conducted the pyrolysis of coating pitch derived from the ethylene tar through thermogravimetry analysis. The thermogravimetry-mass spectrometry and solid-state 13C nuclear magnetic resonance spectroscopy were performed to correlate the structural characteristics with the pyrolysis behavior. Meanwhile, the pyrolysis kinetics were estimated with model-free and model-fitting methods. The TG-DTG results showed that the pyrolysis process was generally divided into drying, fast pyrolysis, and polycondensation stages, accompanied by the decomposition of active functional groups like the aliphatic carbons bonded to oxygen (falO), the pyrolysis of relatively stable groups like the non-protonated aromatic carbon (faH), and the condensation of high bonding-energy aromatic structure like aromatic bridgehead carbon (faB). The activation energy obtained from model-free analysis ranged from 78.12 to 150.92kJ/mol with the increasing conversion, indicating the pyrolysis process as a multi-step reaction mechanism. Furthermore, the reaction model A1/3 (gα=[−ln(1−α)]3) was identified as the most suitable model for the pyrolysis of coating pitch in the conversion range of 0.25-0.8. The modeling values matched well with the experimental data, indicating the accuracy and feasibility of the results.

Spontaneous Formation of Strained Anti-Bredt Bridgehead Alkenes upon Computational GeometryOptimization of Bicyclic β-Halo Carbanions

Bridgehead alkenes are polycyclic molecules bearing at least one C=C bond that includes a bridgehead carbon atom. For small bicyclic systems, these bonds are highly strained due to geometric constraints placed on the sp2 hybridized carbon atoms. These small, strained molecules have been termed “anti-Bredt” alkenes. β-halo carbanions have served as convenient precursors to bridgehead alkenes in experimental studies. We observed that upon attempted computational geometric optimizations (ωB97X-D/aug-cc-pVDZ) of the precursors, spontaneous elimination of the halide occurs along with formation of the anti-Bredt alkene in many cases. Such computational eliminations were shown to faithfully mimic experimentally obtained results. Computational elimination was not observed for [1.1.1] or [2.1.1] frameworks, in agreement with predictions that these bridgehead alkenes are too strained to be formed. However, computational elimination from the [2.2.1] framework was observed to form 1-norbornene, a compound suggested in experimental work to be a reactive intermediate. Similarly, [3.1.1] frameworks and higher led to eliminations upon computational geometric optimization, in agreement with experimental findings. Natural bond order (NBO) calculations of the starting geometries proved to be excellent predictors as to whether elimination would take place. Those precursor compounds exhibiting delocalization energies in the order of 10 kcal/mol between the lone-pair electrons of the carbon atom and σ*C-Br were generally found to undergo elimination. Thus, computational optimization of β-halo substituted bicyclic precursor anions can be used to predict whether strained anti-Bredt alkenes are likely to be formed, thereby saving valuable time and costs in the experimental lab.

Paddlanes revisited: Which are the smallest possible?

AbstractPaddlanes are tricyclic molecules with four bridging chains that share the same two bridgehead carbon atoms. The smallest known paddlane containing only carbon atoms in the main framework has a total of 18 atoms. We utilized computational chemistry (MP2/cc‐pVTZ) to locate the smallest possible all‐carbon paddlanes that meet the criterion suggested by Hoffmann, Schleyer, and Schaefer as being “fleeting,” meaning frequency calculations suggest the structures are energy minima on their respective potential energy surfaces (PES). Our results suggest that paddlane compounds with a total of 10 or fewer atoms can be considered to be non‐viable either because they are not energy minima on the PES or due to strain in the system that manifests as especially long carbon–carbon bonds. Some paddlanes with a total of 11 carbon atoms proved to be energy minima but still exhibited longer carbon–carbon bonds than normal. Finally, several paddlanes with a total of 12 carbons appear to be the least strained since carbon–carbon bond lengths remain reasonable.

Direct Introduction of an Acetyl Group at the α‐Carbon Atom of an Arene Ring through an Amide Photo‐Fries Rearrangement upon Exposure to UV Light

AbstractWe employed an amide photo‐Fries rearrangement for the synthesis benzoheterocyclic compounds and found that direct acylation of the α‐carbon atom in an arene ring can occur upon exposure to ultraviolet (UV) light. In this reaction, the N‐acetyl group of amides underwent rearrangement to the α‐position across the bridgehead carbon atom under UV−C light. The reaction conditions were gentle and safe. Moreover, this reaction proves to be more convenient for selectively manipulating benzoheterocyclic compounds in comparison to traditional approaches involving Lewis acid catalysts or anionic reagents.

Deduction of lignite liquefaction mechanism based on carbon structure analysis and free radical determination

The liquefaction performance of lignite is closely related to its structural evolution. The carbon structure and the free radical concentrations of Naomaohu (NMH) coal and liquefaction products were characterized by modified nuclear magnetic resonance (NMR) spectroscopy and electron paramagnetic resonance (EPR), respectively. The results showed that the oil yield increased gradually with the increase in temperature, and it reached a maximum of 64.91% at 430 °C. The carbon spectrum of the liquefied oil showed that the increase in temperature had little effect on the aromatic carbon connected with the aliphatic carbon, but had a greater effect on the aromatic proton carbon of the liquefied oil. The stability of aromatic carbon in asphaltene was greater than that of aliphatic carbon, and the temperature rise had a significant impact on the different types of aliphatic carbon of the asphaltene. The aromatic side chain of asphaltene gradually broke, and the bridgehead carbon content of the aromatic carbon increased due to the intensification of the condensation reaction at high temperature. On the other hand, the concentration of free radicals in liquefied oil increased with temperature, while the concentration of free radicals in asphaltene first increased and then decreased with temperature, indicating a positive correlation between its change trend and respective yield. With the increase in temperature, the aromatic ring substances with strong bond energy were gradually opened, the side chains were broken, thus forming more low molecular compounds. In summary, based on the above changes in the carbon structure and free radicals, the lignite pyrolysis and liquefaction mechanism have been deduced at the molecular level.

Discovery of sesquiterpenoids from an actinomycete Crossiella cryophila through genome mining and heterologous expression

Genome mining of the Actinomycete Crossiella cryophila facilitated the discovery of a minimal terpenoid biosynthetic gene cluster of cry consisting of a class I terpene cyclase CryA and a CYP450 monooxygenase CryB. Heterologous expression of cry allowed the isolation and characterization of two new sesquiterpenoids, ent-viridiflorol (1) and cryophilain (2). Notably, cryophilain (2) possesses a 5/7/3-fused tricyclic skeleton bearing a distinctive bridgehead hydroxy group. The combined in vivo and in vitro experiments revealed that CryA, the first ent-viridiflorol terpene cyclase, catalyzes farnesyl diphosphate to form the 5/7/3 sesquiterpene core scaffold and P450 CryB serves as a tailoring enzyme responsible for installing a hydroxy group at the bridgehead carbon.

Palladium-Catalyzed α-Arylation of Meyers’s Chiral Bicyclic Lactams and a Deprotonative Ring-Opening Sideline

AbstractDescribed is a deprotonative α-arylation reaction of Meyers’s chiral bicyclic lactams (MCBLs) under palladium catalysis, and a substrate-dependent post-transformation. When the bridgehead carbon of the MCBLs is substituted with a methyl or an ethyl group, the initial arylation product undergoes a further rearrangement reaction to give a conjugated framework. On the other hand, substrates bearing a bridgehead isopropyl or aryl group are converted into the corresponding exo-arylation products. Preliminary studies indicated that the rearrangement pathway was promoted by deprotonation and was independent of palladium catalysis. In addition to mechanistic interests, this study demonstrates a modular and divergent synthesis of functionalized lactams.

The Dynamic Chemistry of Orthoesters and Trialkoxysilanes: Making Supramolecular Hosts Adaptive, Fluxional, and Degradable.

ConspectusThe encapsulation of ions into macro(bi)cyclic hosts lies at the core of supramolecular chemistry. While chemically inert hosts such as crown ethers (synthesis) and cyclodextrins (Febreze) have enabled real-world applications, there is a wider and accelerating trend toward functional molecules and materials that are stimuli-responsive, degradable, or recyclable. To endow supramolecular hosts with these properties, a deviation from ether C-O bonds is required, and functional groups that engage in equilibrium reactions under relatively mild conditions are needed.In this Account, we describe our group's work on supramolecular hosts that comprise orthoester and trialkoxysilane bridgeheads. In their simplest structural realization, these compounds resemble both Cram's crown ethers (macrocycles with oxygen donor atoms) and Lehn's cryptands (macrobicycles with 3-fold symmetry). It is therefore not surprising that these new hosts were found to have a natural propensity to bind cations relatively strongly. In recent work, we were also able to create anion-binding hosts by placing disubstituted urea motifs at the center of the tripodal architecture. Structural modifications of either the terminal substituents (e.g., H vs CH3 on the bridgehead), the diol (e.g., chiral), or the bridgehead atom itself (Si vs C) were found to have profound implications on the guest-binding properties.What makes orthoester/trialkoxysilane hosts truly unique is their dynamic covalent chemistry. The ability to conduct exchange reactions with alcohols at the bridgehead carbon or silicon atom is first and foremost an opportunity to develop highly efficient syntheses. Indeed, all hosts presented in this Account were prepared via templated self-assembly in yields of up to 90%. This efficiency is remarkable because the macrobicyclic architecture is established in one single step from at least five components. A second opportunity presented by dynamic bridgeheads is that suitable mixtures of orthoester hosts or their subcomponents can be adaptive, i.e. they respond to the presence of guests such that the addition of a certain guest can dictate the formation of a preferred host. In an extreme example of dynamic adaptivity, we found that ammonium ions can fulfill the dual role of catalyst for orthoester exchange and cationic template for efficient host formation, representing an unprecedented example of a fluxional supramolecular complex. The third implication of dynamic bridgeheads is due to the reaction of orthoesters and trialkoxysilanes with water instead of alcohols. We describe in detail how the hydrolysis rate differs strongly between O,O,O-orthoesters, S,S,S-trithioorthoesters, and trialkoxysilanes and how it is tunable by the choice of substituents and pH.We expect that the fundamental insights into exchange and degradation kinetics described in this Account will be useful far beyond supramolecular chemistry.

Research on CO2/CH4/N2 competitive adsorption characteristics of anthracite coal from Shanxi Sihe coal mine.

This study aims to solve the problem of unsatisfactory development and utilization of coalbed methane and CO2 storage efficiency. It is focused on the adsorption behavior of CO2, CH4, and N2 in the macromolecular structure model of Shanxi Sihe coal mine anthracite, as well as the competitive adsorption behavior of CO2/CH4 and CH4/N2 binary gas mixtures with different ratios. Experimental analysis such as elemental analysis, solid 13C nuclear magnetic resonance (13C NMR), Fourier transform infrared (FT-IR) spectroscopy, X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD) analysis were used to construct the Shanxi Sihe coal mine model of the macromolecular structure of anthracite coal. The Grand Canonical Monte Carlo (GCMC) and molecular dynamics (MD) simulation methods were used to study the adsorption capacity and heat characteristics of CO2, CH4, and N2 at different temperatures using a molecular model of anthracite coal from Shanxi Sihe coal mine, as well as the competitive adsorption characteristics of CO2/CH4 and CH4/N2 binary mixtures. The mechanism of the influence of temperature and gas properties on the adsorption capacity and heat of adsorption was revealed from a microscopic perspective. The results indicated that the aromatic carbon content of anthracite in the Sihe coal mine, Shanxi is 81.19%, and the ratio Xbp of aromatic bridgehead carbon to surrounding carbon is 0.489. The aromatic structure is mainly composed of pyrene and anthracene. The molecular formula of the macromolecular structure model of anthracite in Shanxi Sihe coal mine is C233H157O13N2. The adsorption capacity and equivalent adsorption heat of the macromolecular model for adsorbing single-component gas CO2/CH4/N2 decrease with the increase in temperature. The temperature has the greatest impact on CO2 adsorption capacity and adsorption heat, followed by CH4 and N2. Under the competitive adsorption conditions of CO2/CH4 and CH4/N2 binary mixtures, the higher the partial pressure of a single-component gas in the mixture, the greater the adsorption capacity of the gas. The difference in the adsorption heat of CH4 and N2 is smaller than that of CH4 and CO2. The conclusions obtained from the study can provide technical and theoretical support for formulating reasonable drainage methods for coalbed methane wells.

Microscopic pyrolysis mechanisms of superfine pulverized coal based on TG-FTIR-MS and ReaxFF MD study

Current studies on coal pyrolysis characteristics mainly focus on macroscopic aspects. Here, the structural properties of coal residues were well characterized based on HRTEM, XPS, and 13C NMR etc., and the macromolecule models were constructed. Combining the small molecule compositions of extracts and the macromolecule models of residues, the multi-component models of raw coals with different particle sizes were successfully constructed. Thus, the microscopic pyrolysis mechanisms of raw coals were obtained by combining TG-MS-FTIR and ReaxFF MD analysis. More importantly, the evolution of chemical bonds and carbon-containing products was discussed. The effect of particle size on microscopic pyrolysis characteristics was focused on. The results show that for smaller particles, the abundant alkylated aromatic and aromatic bridgehead carbon enhances the pyrolysis process. During the primary thermal depolymerization, the conversion of C100+ to C14–C40 and C41–C100 and the generation of pyrolysis gases collectively govern the thermochemical process. For the secondary thermal depolymerization, the release of massive pyrolysis gases is dominant, and most oxygen-containing intermediate groups transform into CO and CO2. In the thermal polymerization stage, the C100+ mainly evolves into C41–C100 and C14–C40, accompanied by the evolution of substantial H2. The microscopic pyrolysis mechanisms shed light on further developing new low-NOx combustion technologies.

Construction and optimization of macromolecular structure model of Tiebei lignite.

Mastering the molecular structure of coal is important for the effective utilization of coal. For a detailed study of the microstructural characteristics of Tiebei lignite, its molecular structure was characterized by elemental analysis, solid 13C nuclear magnetic resonance (13C NMR), Fourier-transform infrared (FT-IR) spectroscopy, X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD). The results showed that the aromatic carbon content of Tiebei lignite was 51.98%, the aromatic carbon structure was mainly composed of benzene and naphthalene, and the ratio of aromatic bridgehead carbon to surrounding carbon Xbp was 0.14. Oxygen existed in phenol, ether, carbonyl, and carboxyl; nitrogen-containing structures mainly existed in the form of pyrrole and pyridine; sulfur mainly existed in thiophene sulfur; and aromatic substitution was mainly in the form of trisubstitution. The molecular formula of the macromolecular structure model of Tiebei lignite was C190H161O57N2, and the 13C NMR spectrum of the model was in good agreement with the experimental results, which fully verified the accuracy of the macromolecular structure model of Tiebei lignite. The construction of a macromolecular structure model of Tiebei lignite is essential to intuitively understand the molecular structure characteristics of Tiebei lignite and to provide theoretical support and guidance for the micromechanism research and prevention of lignite spontaneous combustion and other disasters.

Structural Characterization and Molecular Model Construction of High-Ash Coal from Northern China.

High-ash coal, also known as low-grade coal, has becomes a viable alternative in recent years to high-quality coal because available resources have become increasingly scarce due to extensive mining activity. This work aims to provide a comprehensive understanding of the structural characteristics of high-ash coal and construct a plausible molecular structure to elucidate its chemical reactivity in future applications. Its properties were investigated using Solid-state 13C nuclear magnetic resonance (13C NMR), X-ray photoelectron spectroscopy analysis (XPS), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FT-IR). The molecular structure was constructed and validated using Material Studio, LAMMPS Software Package, and MATLAB program. The characterization results revealed that high-ash coal contains 72.15% aromatic carbon, significantly surpassing the percentage of aliphatic carbon (27.85%). The ratio of bridgehead carbon to peripheral aromatic carbon was calculated as 0.67, indicating that the pentacene is the main carbon skeleton form in the high-ash coal structure. Furthermore, oxygen-containing functional groups presented as C=O/O-C-O, C-O, and COO- within the structure along with pyridine and pyrrolic structures. Consequently, the molecular structure comprises pentacene with aliphatic carbon chains, such as methylene, that connect the benzene rings and form a three-dimensional network. The results of a simulated IR spectrum and contact angle simulation aligned with the experimental results, validating the molecular structure of high-ash coal. The chemical formula for the high-ash coal model was determined as C203H189N7O61S with a molecular weight of 3734.79.

Correction of sideband effects of nuclear magnetic resonance carbon spectrum in coal and its application in coal structure analysis

AbstractIn the nuclear magnetic resonance (NMR) test of coal, when the spinning frequency of magic‐angle spinning (MAS) is less than the frequency range of chemical shift anisotropy, serious aromatic carbon spinning sidebands will appear. Existing solutions to the sideband effect, such as changing the MAS frequency, inserting total suppression of sidebands (TOSS) pulse sequences, or simply defining the peak after chemical shift of 200 ppm as the sideband peaks generated by aromatic carbon peak, multipling the identified sideband integral by 2 and adding to the main peaks of protonated aromatic carbon and aromatic bridgehead carbon. None of these methods can reasonably correct for the sideband effect and cause errors to accurately quantifying the carbon structure parameters. Compared with 13C nuclear magnetic resonance (13C NMR) spectrum without sideband suppression (13C CP‐MAS NMR) and 13C NMR spectrum under sideband suppression conditions (13C CP‐MAS/TOSS NMR), according to the chemical shifts of the main peaks of four aromatic carbons, namely protonated aromatic carbon, aromatic bridgehead carbon, alkylated aromatic carbon and oxygen‐linked aromatic carbon, combined with the MAS frequency, the first‐ and second‐level sideband peaks generated by four types of aromatic carbons were accurately located and quantified, and they were added to the corresponding aromatic carbon main peaks in 13C CP‐MAS/TOSS NMR spectrum, thus realizing the accurate correction of sideband effect of the solid‐state 13C NMR spectrum of coal samples. The relative area of corrected aliphatic carbon, carbonyl (carboxyl) carbon, and various aromatic carbons were recalculated, and more accurate carbon structure parameters were obtained, which is significant for studying the coal structure from a microscopic perspective.

Synthesis of 5-Hydrazino-2-cyclopentenone Derivatives by a Gold(I)-Catalyzed Cycloisomerization/Hetero-Diels-Alder/Ring-Opening Tandem Reaction of Enynyl Acetates.

A highly efficient, one-pot synthesis of ring-fused 5-hydrazino-2-cyclopentenone derivatives is achieved by a gold(I)-catalyzed cycloisomerization/hetero-Diels-Alder/ring-opening tandem reaction of suitable enynyl acetates. By mixing the latter with a dialkylazodicarboxylate in the presence of a gold(I) catalyst, the 1,3-acyloxy migration/Nazarov cyclization process leads to dienyl acetate intermediates which are trapped by the heterodienophile present in situ. This provides strained intermediates which undergo highly regioselective ring opening by a retro aza-Michael reaction promoted by traces of water, eventually yielding the target compounds. Six- and seven-membered ring-fused cyclopentenones and piperidine- and tetrahydropyran-fused cyclopentenones bearing a pendant hydrazino functionality on a bridgehead carbon atom can be obtained in high yield (68-96%) by this approach.

Magnetic Shielding Analysis of Bonding in [1.1.1]Propellane.

The bonding in [1.1.1]propellane, bicyclo[1.1.0]butane, bicyclo[1.1.1]pentane, tetrahedrane, and cyclopropane is investigated by analyzing changes in the off-nucleus isotropic magnetic shielding within the space surrounding each of these molecules and, for [1.1.1]propellane, by examining also the diamagnetic and paramagnetic contributions to this shielding. Any shielding arising from the two "exo" sp3-like hybrid atomic orbitals on the bridgehead carbon atoms that have been used to support the idea of an inverted bond between these two atoms is found to be almost entirely contained within the [1.1.1]propellane cage and to contribute to a strongly shielded central region. This strongly shielded region suggests the establishment of a mainly covalent bonding interaction involving all carbon atoms that cannot be straightforwardly decomposed into contributions from individual carbon-carbon bonds. The emergence of the strongly shielding central region is traced by comparing the shielding variations in and around molecules with one three-membered carbon ring (cyclopropane), two fused three-membered carbon rings (bicyclo[1.1.0]butane), and three fused three-membered carbon rings ([1.1.1]propellane).

Finding activity through rigidity: syntheses of natural products containing tricyclic bridgehead carbon centers.

Covering: up to 2022Tricyclic bridgehead carbon centers (TBCCs) are a synthetically challenging substructure found in many complex natural products. Here we review the syntheses of ten representative families of TBCC-containing isolates, with the goal of outlining the strategies and tactics used to install these centers, including a discussion of the evolution of the successful synthetic design. We provide a summary of common strategies to inform future synthetic endeavors.

Ruthenium(II)-Catalyzed Tandem C-H Allylation and [3 + 2] Dipolar Cycloaddition to Construct Bridged Tetracycles.

The ruthenium(II)-catalyzed tandem C-H allylation and intramolecular dipolar cycloaddition between azomethine imines and 2-methylidenetrimethylene carbonate is described herein. The initially formed β-substituted allyl fragment could trigger the exotype [3 + 2] cycloaddition with the polar azomethine group, resulting in the formation of bridged tetracycles bearing a hydroxymethylene group at a bridgehead carbon center. A wide substrate scope and broad functional group compatibility were observed. The gram-scale synthesis and synthetic transformations demonstrate the synthetic utility of this process.