Application gaps in Chemistry

Representative open questions

Showing 30 of 39 — one per source paper, highest-quality first.

• Mechanistic investigations of the formation of multifunctional products from the multi-generation ●OH oxidation of styrene (2026) · doi

  The mechanism predicts that further oxidation of third-generation products may yield compounds with sufficiently low volatility to nucleate new aerosol particles; direct chamber or smog chamber experiments measuring new particle formation rates and growth kinetics from these predicted ultra-low volatility organic compounds (ULVOCs) have not been conducted.

• High-Entropy Catalysts for Biomass-Derived Chemicals Valorization: Mechanisms, Applications, and Opportunities (2026) · doi

  High-entropy catalysts (HECs) have only been applied to seven specific biomass valorization reactions (HMF oxidation to FDCA, HMF and furfural hydrogenation, furfural oxidation condensation, lignin depolymerization, glucose to glucaric acid, and glycerol oxidation), while over 200 types of high-value chemicals can be synthesized from biomass platform compounds. The application scope must be expanded to retro-aldol condensation pathways, HMF transformation to levulinic acid and alkyl levulinates, and furfural conversion to its 80+ derivative chemicals.

• Olympian colour chemistry (2012) · doi

  Current photochromic dye technology with additive cocktails (hindered amine light stabilisers, triplet state quenchers, UV absorbers) achieves only an order of magnitude lifetime extension, but this remains insufficient for smart window applications requiring long-term regular and prolonged exposure to strong sunlight. The specific mechanisms by which these additives interact with spirooxazine and naphthopyran dyes to extend lifetime without compromising activation kinetics need further systematic investigation.

• Synthesis of Tetravalent Boron Complexes with Pyrazolone-Based Ligand and their Drug-Likeness (2026) · doi

  Although the paper demonstrates that boron complexes with pyrazolone ligands pass drug-likeness filters, no in vitro cytotoxicity, antimicrobial, or antifungal screening assays were performed to identify specific pharmacological targets or biological activities, unlike referenced boron-containing compounds evaluated against glioblastoma, endometrial cancer, or biofilm-forming pathogens.

• Physical Organic Chemistry (POC) Makes Chemistry a Science: A Personal Reflection on POC (2016) · doi

  The artificial intelligence approach for discovering rules and laws in physical organic chemistry has been demonstrated only for explosive materials' detonation velocity prediction. The methodology needs to be systematically applied across other classes of organic compounds and reaction types to establish whether the AI-discovered rules (such as the C-O bond correlation) generalize beyond energetics chemistry.

• The advent of macrocyclic chemistry (2012) · doi

  The paper notes that azamacrocycles can function similarly to porphyrins in catalytic and redox applications by incorporating them into larger structures, but does not specify which catalytic reactions, redox potentials, or protein-like structures have been attempted or remain untested.

• Analytical Techniques in Chemistry (2019) · doi

  While the paper describes pH metric titrations for strong acid versus strong base reactions, there is no discussion of the applicability and end point detection accuracy of pH metry in weak acid-weak base, weak acid-strong base, or weak base-strong acid titration scenarios, which represent the majority of practical analytical chemistry applications.

• The Basis of a Greener Analytical Chemistry (2011) · doi

  While the paper demonstrates waste reduction from 960 to 27 mL/h using micropump multicommutation for carbaryl determination with p-aminophenol, the applicability of this automation approach to other pesticide classes and toxic metal analyses has not been systematically evaluated across different analyte types and matrices.

• Initial organotin chemistry (2014) · doi

  The synthesis of trialkyltin compounds R3SnX via the Kocheshkov redistribution reaction (Kocheshkov comproportionation) is mentioned as discovered by Buckton but the scope of this reaction with different alkyl groups (beyond ethyl and methyl) and leaving groups X remains unexplored.

• Bis (N-Heterocyclic Carbene) Palladium Complex Immobilized Onto Fe3o4@Sio2 as a Catalyst for Sonogashira (Amine/Copper Free) and Hiyama Coupling of Arbr/Cl in Green Media (2026) · doi

  The paper evaluates substrate scope with electron-withdrawing and electron-releasing substituents on aryl bromides, as well as phenyl and ethynyl derivatives of terminal alkynes, but does not test sterically hindered aryl chlorides or conjugated alkynes. Systematic investigation of bulky ortho-substituted aryl chlorides and internal alkynes with the Pd-NHC/Fe3O4@SiO2 catalyst would clarify its scope limitations.

• My journey in the CO2-chemistry wonderland (2017) · doi

  The ketal-mediated synthesis of cyclic carbonates (cyclohexanone + ethylene glycol → ketal → sc-CO2 treatment → cyclic ethylene carbonate) requires quantitative recovery of the cyclohexanone mediator for economic viability, but the paper does not specify recovery yields, separation methods, or cost-benefit analysis needed to determine if this pathway is economically competitive versus direct epoxide carboxylation routes.

• Organometallic Chemistry of Heterocycles (2010) · doi

  The combinatorial ligand design approach linking two different donor functions (e.g., polypyrazol-1-yl aluminates and poly-imidazol-2-ylidene borates) for catalytic applications has been established, but systematic screening of catalytic efficacy across diverse reaction types and substrate scopes for these dual-donor azole systems has not been reported.

• Resonance-enhanced multiphoton ionization time-of-flight mass spectrometry for the real-time analysis of a retronasal aroma compound from a cumin sandwich (2026) · doi

  The study analyzed aroma release from cumin alone; it remains unspecified whether the volatilization behavior and release kinetics derived from REMPI-TOFMS measurements of p-cymene will transfer to or differ significantly in food systems where cumin is mixed with other spices or ingredients that alter oral cavity pH, temperature, or saliva composition.

• cAMPS derivatives. A minireview over synthetic medicinal chemistry (2019) · doi

  The synthesis of membrane-permeable 8-substituted cAMPS prodrugs (compounds 73, 75, 77, 82) is described, but no systematic evaluation compares membrane penetration efficiency, intracellular activation rates, or receptor selectivity across the different prodrug scaffolds (pivalate vs. p-isobutyryloxybenzyl vs. p-acetoxybenzyl) in the same cell type or tissue.

• Special issue: Plant synthetic biology (2020) · doi

  The sources of chloroiodobenzene isomers and 1-iodo-4-nitrobenzene detected in Moscow snow samples remain unidentified; the authors note that iodobenzenes are unusual environmental contaminants used in organic chemistry synthetic reactions and functionalization, but pinpointing their specific anthropogenic sources requires targeted source apportionment studies beyond current analytical identification.

• Design of a green ammonia production process by machine learning (2026) · doi

  The integration of upstream feedstock production (hydrogen and nitrogen sourcing for green ammonia synthesis) with the optimized reactor process design was identified as future work but not executed; the machine learning model's ability to jointly optimize feedstock production parameters and reactor operating conditions remains unexplored.

• Flow Chemistry as a Drug Discovery Tool: A Medicinal Chemistry Perspective (2018) · doi

  While high-temperature Boc deprotection in flow achieves quantitative yields across a broad substrate scope (Scheme 20), the paper does not address whether the 300°C/2 min protocol at 100 bar is applicable to Boc-protected substrates containing acid-labile or thermally sensitive functional groups (e.g., acetals, vinyl ethers, or certain heterocycles) commonly encountered in drug discovery.

• Preparation and Biological Activity of Molecular Complexes Based on Secondary Metabolites of Glycyrrhiza Glabra L. and Sophora Japonica L. (2026) · doi

  The optimal GA:Rutin molar ratio of 4:1 identified for capillary-protective activity requires in-depth investigation of dose-response relationships, pharmacokinetic parameters (absorption, distribution, metabolism, excretion), and bioavailability enhancement mechanisms in relevant biological models.

• Flow Chemistry in Drug Discovery: Challenges and Opportunities (2021) · doi

  The paper states that fully integrated design-synthesize-test-purify cycles can combine algorithmic predictions with biological screening in automated platforms, but does not specify the integration requirements between flow chemistry synthesis modules and downstream purification/characterization modules, nor provides data on throughput compatibility between synthesis and purification rates in integrated systems.

• The Burgeoning of Mechanically Interlocked Molecules in Chemistry (2019) · doi

  While mechanically interlocked molecules have been investigated in solution, their deposition onto substrates and the effect of thin films on molecular behavior must be understood properly for on-surface applications. Specifically, the switching behavior and orientation changes of rotaxane monolayers on various substrates (glass, silicon) need systematic investigation to enable multiresponsive multilayer surface design.

• A universal atomically dispersed cobalt catalyst for alkylation of ketones alcohols and lignin-derived compounds (2026) · doi

  The Co@NC-PPDA catalyst has been demonstrated for C-alkylation of ketones, secondary alcohols, and lignin model compounds at 120-150 °C, but direct application to industrial-scale lignin valorization with crude kraft lignin or technical lignin streams has not been evaluated. The scope remains limited to structurally simple lignin-derived compounds rather than complex polymeric lignin feedstocks.

• Recent developments in the chemistry of azaferrocenes (2010) · doi

  W(CO)₅-containing azaferrocenes 38-39 were evaluated as IR-active spectroelectrochemical markers via cyclic voltammetry and FTIR spectroelectrochemistry, but their actual application to biomolecule detection and quantification, as well as comparison with existing organometallic markers in biological matrices, has not been demonstrated.

• Thermodynamics in Chemistry (2012) · doi

  The paper states that gas-phase reactions often require specific catalysts whose development demands enormous cost and effort, and that products may react further depending on catalyst and environmental variables, but does not address how to systematically predict which side reactions will dominate under specific catalyst-temperature-pressure combinations in ammonia synthesis.

• Fine and hyperfine interactions with multi-level spin relaxation of the purified Giese-salt in veterinary medicine: Prussian blue compound ammonium-ferric-hexacyano-ferrate (2026) · doi

  The veterinary pharmaceutical effectiveness of purified Giese-salt AFCF (86–266 times more effective than ion exchangers for radiocesium remediation) is documented, but the biomolecular mechanism linking the magnetic short-range order, ferromagnetic cluster properties (S = 66, KV/kBT = 4.08), and cesium ion binding/sequestration has not been established; in vitro radiocesium adsorption studies on AFCF samples with characterized magnetic relaxation parameters are required.

• Flow Chemistry in Medicinal Chemistry: Applications to <scp>Bcr</scp> ‐ <scp>Abl</scp> Kinase Inhibitors (2022) · doi

  The paper employs fluorescence-based assays with optical cartridge plate readers but does not address how assay standardization protocols should account for reagent stability degradation during continuous extended operation of the integrated flow-chemistry-to-bioassay platform.

• Formal organocatalytic fluoronitromethane addition to tetrahydroisoquinolines through a CDC process (2026) · doi

  While the scope evaluation tested tetrahydroisoquinolines with various N-protecting aromatic groups (p-Me, halogens, p-CF₃, p-OMe), the methodology has not been evaluated on aliphatic N-substituents or N-unprotected tetrahydroisoquinolines. The compatibility of the Rose Bengal photocatalytic system with alternative nitrogen protection strategies beyond aromatic sulfonamides requires systematic study.

• ReaxFF simulations on molecular entrapment capability and gas sensor performance of some volatile organic compounds by a novel functional tubular-helix nanostructure doped sulfur (2026) · doi

  The paper does not address how the proposed sulfur-doped tubular-helix nanostructure could be synthesized at scale or integrated into practical gas sensor devices, limiting assessment of real-world applicability beyond computational predictions.

• Lu2CrMnO6–Pm-g-C3N4 supported dendritic nanosilica as a recyclable green catalyst for eco-friendly synthesis of N-[(2-hydroxyethoxy)carbonyl] glycine from carbon dioxide (2026) · doi

  The catalyst was tested under specific optimized conditions (80 °C, 30 min, solvent-free) with a limited range of substrates; broader applicability to other epoxide substrates, reaction temperatures, pressures, and solvent systems remains unexplored.

• Chemistry Teacher International, Best Practices in Chemistry Education (2020) · doi

  Chemistry education conferences in different regions (NICE, Eurovariety, ACRICE) should serve as sources for articles, suggesting a need to systematically integrate global conference proceedings into the journal.

• Green Chemistry Metrics in Analytical Chemistry (2024) · doi

  The use of 10 mg of a sorbent looks environmentally friendly if one does not take into account that 100 mL of a toxic or volatile organic solvent was spent for its synthesis, indicating a need to evaluate not only the chemical analysis procedure itself but also the processes preceding it.