Application gaps in Chemistry

Representative open questions

Showing 30 of 94 — one per source paper, highest-quality first.

• Real-time P$$_2$$O$$_5$$ quantification in industrial phosphoric acid using laser-induced breakdown spectroscopy: a paradigm shift in process analytical chemistry (2026) · doi

  The calcium (Ca II doublet at 393-397 nm and Ca I lines at 315-318 nm) signals were identified as highly important VIP features due to geochemical correlation with phosphate in source material, but the quantitative relationship between calcium content variations and P2O5 measurement accuracy, and whether Ca interference requires explicit correction for real-world industrial samples, has not been characterized.

• 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.

• Green Dispersive Liquid–Liquid Microextraction Using an Octanol-Menthol-Based Deep Eutectic Solvent for Sensitive UV–Vis Determination of Rhodamine B in Food and Water Samples (2026) · doi

  The DLLME-OCT-MEN-DES method achieved a LOD of 5.1 µg L⁻¹, which is insufficient for ultra-trace level detection applications requiring concentrations below 5 µg L⁻¹, such as advanced environmental monitoring, forensics, or medical applications where higher sensitivity is critical.

• 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.

• WITHDRAWN: Combinatorial Chemistry Online Volume 15, Issue 11, November 2013 (2013) · doi

  Parallel high-throughput screening of polymer vectors for nonviral gene delivery by Rinkenauer et al. identified structure-property relationships for transfection, but systematic investigation of how polymer library diversity affects transfection efficiency across different cell types and genomic targets remains incomplete.

• Methyl 2-deoxy-3,5-di-O-p-toluoyl-α-d-ribofuranoside: isolation, crystal structure and conformation (2026) · doi

  The compound's utility as a glycosylation donor (as referenced in synthetic applications, refs. 2-3, 12) is not experimentally validated in this work; reactivity studies examining glycosylation efficiency, regioselectivity, and stereoselectivity with various nucleophiles are absent.

• 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.

• Introduction to Surface Chemistry Essentials (2013) · doi

  The paper states that milk emulsion chemistry is 'one of the most complex, and has still not been well investigated,' particularly regarding the interfacial composition and stability mechanisms in water-in-oil-in-water (W/O/W) systems. Detailed investigations of protein-lipid interfacial interactions and droplet coalescence kinetics in dairy emulsions would clarify biological emulsion design principles.

• 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.

• Using quantum chemistry to estimate chemical shifts in biomolecules (2020) · doi

  Conformational sampling effects on quantum chemical NMR predictions have been addressed for proteins [27], but the methodology has not been applied to characterize Watson-Crick versus Hoogsteen base pairing in DNA-protein complexes where multiple conformational states coexist.

• Chemistry of Carbon and Hydrogen (2019) · doi

  The paper mentions that 13C isotope finds use in reaction rate determination and mechanism elucidation for various reactions, but does not specify which reaction types (e.g., substitution, elimination, addition) have been studied or which remain unexplored using 13C spectroscopic analysis and isotopic labeling techniques.

• 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.

• Coordination chemistry of tris(azolyl)phosphines (2018) · doi

  Tris(azolyl)phosphines possess potential dual coordination sites (nitrogen atoms on azolyl rings and phosphorus apex), yet very few coordination studies have exploited both binding sites simultaneously in bimetallic or heterodinuclear complexes; this represents an unexplored avenue for tuning metal-metal electronic interactions through systematic variation of one metal center while the second binding site remains available for surface fixation or catalysis.

• Quinolines, a perpetual, multipurpose scaffold in medicinal chemistry (2021) · doi

  The quinoline peptide derivatives (161-165) demonstrated antimicrobial activity against five bacterial and fungal species, but resistance development mechanisms and the potential for cross-resistance with existing quinolone antibiotics have not been evaluated through serial passage or time-kill studies.

• 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.

• Chemistry and Pharmacy (2012) · doi

  The paper traces how alkaloid isolation and quinine synthesis exemplified the quest for pure active ingredients in modern pharmacy, but does not systematically examine what chemical and pharmaceutical criteria determine whether complex plant-derived remedies should be decomposed into isolated active ingredients versus preserved as multi-component preparations. Research comparing therapeutic efficacy, safety profiles, and mechanism of action between isolated alkaloids and their parent plant extracts would address this gap.

• 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.

• Shilov alkane platinum chemistry: 45 years (2015) · doi

  The heterogenized PtII complex catalytic system with triazine-based framework (2) for methane oxygenation achieves the highest catalytic rate but requires investigation of methods to mitigate the corrosive medium conditions and reduce the relatively high temperatures needed for alkane platinum oxidation reactions.

• Arene Ruthenium Complexes in Supramolecular Chemistry (2018) · doi

  Only one example of metallomesogen containing arene ruthenium complexes has been reported (the three-component system with pyrenyl-functionalized poly(arylester) dendrimers). The facility to modify and interchange different components suggests systematic exploration of alternative dendrimer structures, varied anion types, and different arene ligands is needed to establish design principles for arene ruthenium liquid-crystalline materials.

• 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.

• Origins of Green Analytical Chemistry (2011) · doi

  Table 1.3 shows growth in green analytical chemistry literature across multiple analytical techniques (spectroscopy, chromatography, electrochemistry, flow analysis), but the paper does not address which emerging analytical methodologies (e.g., miniaturized sensors, ionic liquids, plasma-based techniques) have achieved practical implementation at industrial or regulatory scales. Comparative assessment of scalability barriers for green alternatives in routine analytical practice is absent.

• Bioactive compounds from the cultured lichenmycobiont of Nigrovothelium inspersotropicum (2026) · doi

  Compound 1 demonstrated moderate HIV-1 reverse transcriptase inhibition with an IC50 of 145.5 ± 5.7 μM, which is substantially higher than the reference drug Nevirapine (1.6 ± 0.1 μM). Structure-activity relationship studies and chemical derivatization of compound 1 are needed to identify modifications that could enhance reverse transcriptase binding affinity and reduce the IC50 value to clinically relevant ranges.

• Laws in Chemistry (2012) · doi

  The paper discusses computational chemical models as 'overt' alternatives to bench-top reactions but does not investigate whether wave function-based computational models that generate quantitative predictions satisfy different criteria for law-likeness than qualitative chemical equations. The relationship between Berzelian mechanistic explanations and quantum mechanical computations in grounding chemical necessity remains unexamined.

• Atmospheric oxidation chemistry of hexafluoroisobutylene initiated by OH radical: Kinetics and mechanism (2021) · doi

  The study focused exclusively on OH radical-initiated oxidation; reactivity of (CF3)2C=CH2 with other atmospheric oxidants (Cl atoms, O₃, NO₃ radicals) at varying temperatures and pressures must be characterized to fully assess the compound's atmospheric degradation pathways and environmental persistence.

• 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.