Data gaps in Chemistry

Representative open questions

Showing 30 of 45 — 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 volatility predictions for third-generation closed-shell products (S47, S51, S58, S62) rely on SIMPOL.1 estimation methods; direct experimental measurements of saturation vapor pressure and condensation behavior of these highly oxygenated and nitrogenated compounds under atmospheric conditions are needed to validate particle formation potential.

• QM/MM hybrid simulation of enzyme-Mn synergistic catalysis for quinazolinones: computational determination of activation energy and transition state (2026) · doi

  The basis set sensitivity analysis (6-311++G(d,p), def2-TZVP, cc-pVTZ) showed deviations ≤0.2 kcal/mol for quinazolinone synthesis, but this finding was limited to activation energy predictions; systematic comparison of basis set performance for transition state geometric parameters (C-N bond length, Mn-O coordination) and vibrational frequency calculations remains incomplete.

• Cyclooligophosphanes and their coordination chemistry (2021) · doi

  The coordination chemistry of cyclooligophosphanes with transition metals has been documented for specific ring sizes (tetraphosphanes, hexaphosphanes), but systematic coordination studies with larger ring systems such as octadecaphosphanes (P18) and icosaphosphanes (P20) remain unexplored, limiting understanding of how ring size affects metal binding modes and complex stability.

• Olympian colour chemistry (2012) · doi

  Side-reaction rate constants are reported as small for spirooxazines and naphthopyrans, but the paper provides no quantitative comparison of these constants across structural variants or under different light exposure intensities and wavelengths, making it difficult to predict fatigue accumulation timescales for specific dye designs in real-world lens applications.

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

  The paper evaluated six boron-pyrazolone complexes (MPAP-1 to MPAP-6) against five drug-likeness rule sets but did not investigate blood-brain barrier (BBB) permeability, plasma protein binding, or renal clearance prediction specific to the charged or lipophilic nature of these tetravalent boron coordination compounds.

• The advent of macrocyclic chemistry (2012) · doi

  The thermodynamic stability enhancement of macrocyclic ligand compounds depends on both cation and ring size with complex enthalpic and entropic components, but the paper does not specify which specific cation-ring size combinations have been systematically studied or which combinations remain unexplored.

• Analytical Techniques in Chemistry (2019) · doi

  The advantages of potentiometric titrations state that the method works for dark-colored solutions where indicators fail, but the paper does not provide quantitative data on the concentration limits or color intensity thresholds at which indicator-based titrations become unreliable compared to potentiometric methods.

• Basic Organometallic Chemistry (2016) · doi

  While ferrocene's application in promoting smoke-free fuel combustion and preventing engine knocking is mentioned, the paper provides no quantitative data on combustion efficiency improvements, emission reduction percentages, or optimal ferrocene concentrations for these fuel applications.

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

  The energy consumption reduction claims for miniaturization and automation strategies in green analytical chemistry lack specific quantification; comparative energy consumption data (kWh per sample) across classical FIA, SIA, solenoid valve multicommutation, and micropump systems are not provided.

• 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

  Large variability in start time (standard deviation 2.8 s) and especially end time (standard deviation 8.6 s) for retronasal aroma release was attributed to individual differences across four panelists, but the study did not systematically characterize which physiological or anatomical factors (saliva secretion rate, oral cavity geometry, breathing pattern) drive this inter-individual variability in REMPI-TOFMS measurements.

• Chemistry and Pharmacy (2012) · doi

  The paper argues that chemistry's productive power—particularly in organic synthesis generating millions of novel compounds annually—is understudied by philosophers of chemistry, yet provides no framework for assessing how this synthetic capacity in pharmaceutical chemistry relates to actual drug discovery rates, market approval, or clinical efficacy. A quantitative analysis tracking synthesis rates of novel compounds against successful pharmaceutical candidates would illuminate this relationship.

• Multicomponent reactions in crop protection chemistry (2020) · doi

  Downy mildew disease control compounds have been discovered through multicomponent reactions, but comparative efficacy and selectivity data against resistant pathogen populations and alternative crop protection targets remain absent from the literature.

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

  While hexamethylphosphoramide (HMPA) was identified in Moscow snow samples with multiple known applications (polymer solvent, polymerization catalyst, UV stabilizer, flame retardant, anti-freezing additive), the specific emission pathways and dominant sources contributing to its environmental presence remain unclear and require source-receptor modeling studies specific to HMPA.

• Porous crystals as scaffolds for structural biology (2020) · doi

  Post-crystallization covalent guest installation in DNA scaffold crystals has been demonstrated (ref. 23), but the efficiency rates, reaction conditions, and residual reactivity of installed guest molecules within the crystal lattice remain unquantified for complex multi-guest loading scenarios.

• Self-Assembly of Complementary Components Using a Tripodal Bismuth Compound: Pnictogen Bonding or Coordination Chemistry? (2021) · doi

  The paper examines self-assembly in benzene-d6 solution via NMR but does not systematically investigate how solvent polarity or donor capability affects the pnictogen bonding vs. coordination chemistry equilibrium. Testing the 2·Py3 system in solvents ranging from non-polar (CCl4) to polar (DMSO) would establish whether solvent environment modulates the interaction mechanism.

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

  The paper discusses solubility limitations in flow chemistry compared to parallel batch approaches (which can perform diverse chemistries regardless of solvent mixture solubility), but provides no concrete data on the specific solubility thresholds that prevent flow chemistry applicability or systematic guidelines for predicting which reaction classes will face solubility constraints in continuous flow reactors.

• Dynamic Chemistry of Anion Recognition (2011) · doi

  The paper demonstrates exceptional sulfate selectivity against selenate in crystalline frameworks with Li+ cations yielding pyrite topology, but competitive crystallization selectivity data comparing sulfate against carbonate and selenate in the same Li-based system are not provided. Systematic binding affinity measurements and selectivity ratios across different divalent oxoanions in identical frameworks are needed.

• Progress in molecular uranium-nitride chemistry (2014) · doi

  Deuterium labelling confirmed that transient nitride intermediates formed during azide decomposition react with toluene solvent in the absence of sodium ion stabilization (forming primary amido complex 30), but the scope of solvent molecules and competing side-reactions under varying reaction conditions has not been systematically explored.

• Applications of Isatin Chemistry in Organic Synthesis and Medicinal Chemistry (2013) · doi

  The 9-demethylneopeltolide analogue showed equipotent or superior activity to neopeltolide in P388 murine leukemia cells and can be synthesized more readily, but its mechanism of action against cytochrome bc1 and its activity profile across the broader panel of cancer cell lines tested for native neopeltolide (A549, PANC-1, DLD-1, HCT116, PC3) have not been evaluated.

• When Stereochemistry Raised Its Ugly Head in Coordination Chemistry—An Appreciation of Howard Flack (2020) · doi

  Crystal Structure Databases lack routine inclusion of Flack parameter values in their standard data fields, making it impossible to systematically query fundamental questions about chiral coordination compounds. This database gap prevents data-mining activities from answering basic questions such as the total number of structurally characterized chiral coordination compounds or the prevalence of asymmetric crystallization in coordination networks.

• Sustainable Biginelli chemistry: Indian contributions to green multicomponent synthesis (2026) · doi

  Plant extract catalysts (five different extracts) were used for DHPM synthesis with yields of 50–95%, but the paper lacks identification of the specific active chemical components within these extracts and their individual catalytic contributions to the Biginelli transformation.

• Coordination and catalytic chemistry of phosphinoferrocene carboxamides (2017) · doi

  The substrate scope study for acyl chloride coupling with boronic acids (Scheme 44) identified that proper selection between complementary routes (route A vs. route B) is essential for good yields, but the paper does not specify which substrate classes require which route or provide predictive guidelines for ligand 106·HCl catalyst selection.

• Chemistry of sterically demanding dppf-analogs (2021) · doi

  For Ni-catalyzed C-N cross-coupling, CF3-substituted dppf-analogs (14 and 15) show little effect compared to unsubstituted dppf despite similar 31P NMR shifts; direct measurement of Ni-phosphine binding affinities and electronic properties of these ligands through complementary spectroscopic methods (e.g., FTIR, UV-vis) is needed to explain the lack of electronic differentiation.

• 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 study examined one industrially-synthesized purified AFCF sample; variability in structural details and magnetic properties across AFCF batches from different synthesis processes or manufacturers has not been systematically investigated, limiting generalization of the reported multi-level relaxation parameters and ferromagnetic transition temperatures to other Prussian blue compound sources used in veterinary radiocesium treatment.

• From Coordination Chemistry to Adaptive Chemistry (2018) · doi

  The ligand crossover process observed between two homo-metallo-dynamer films at 50°C for 24 hours without solvent or catalyst suggests kinetic and thermodynamic factors controlling monomer exchange, but systematic kinetic studies characterizing the rates of constitutional metal-ligand exchange reactions, activation barriers, and equilibrium distributions as functions of temperature, metal identity, and ligand structure are absent.

• Chiral configurations in cyclophosphazene chemistry (2015) · doi

  The diastereoisomeric ratio of 1:2:1 for compounds 139a-c has been experimentally confirmed for tri-spirane cyclophosphazenes with two chiral centers, but this relationship has not been systematically investigated for spirane systems with more than four equivalent centers of chirality or for non-equivalent chiral center combinations.

• Investigation of the effect of solvent polarity and viscosity on the Stokes shift of chromeno[2,3-b]indoles (2026) · doi

  The cited photophysical characterization studies employ femtosecond fluorescence and transient absorption spectroscopy on GFP chromophore analogs and malachite green, but comparable ultrafast spectroscopic measurements explicitly designed to probe the excited-state relaxation pathways and internal conversion rates of chromeno[2,3-b]indoles across different solvent polarities and viscosities are not reported in the reference list.

• 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

  While helical nanostructure geometry is proposed as advantageous for VOC sensing, quantitative investigation of how specific geometric parameters (pitch angle, helix diameter, tubular wall thickness) affect gas sensor performance through ReaxFF simulations has not been systematically explored.

• Nanoparticle Growth by Particle Phase Chemistry (2017) · doi

  Whether a nanoparticle will grow to a CCN-relevant size depends on its growth rate relative to loss rate from coagulation or scavenging by pre-existing aerosols, creating uncertainty in prediction models.

• Homoleptic triorganotin(IV) organoselenolates of type R3Sn(SeCH2CH2pz) (2025) · doi

  The coordination geometry of aliphatic compounds 1-3 was assigned based on NMR coupling constants in solution at room temperature, but solid-state structures for these compounds were not determined.