Pyridinium bromide

Q. Basic: What are the recommended methods for synthesizing alkyl-substituted pyridinium bromide ionic liquids, and how do alkyl chain lengths influence their physicochemical properties?

Answer:
Alkyl-substituted pyridinium bromides (e.g., 1-dodecylthis compound, C₁₂PyBr) are synthesized by quaternizing pyridine with alkyl bromides. For example, 1-hexadecylthis compound (C₁₆PyBr) is prepared by reacting pyridine with 1-bromohexadecane under reflux conditions in anhydrous solvents . The alkyl chain length significantly impacts properties such as melting point, solubility, and surface activity. Longer chains (e.g., C₁₈) enhance hydrophobicity and reduce critical micelle concentration (CMC), making them suitable for applications like surfactants or electrolytes . Structural confirmation requires ¹H NMR (e.g., using deuterated DMSO for resolving alkyl and pyridinium proton signals) and elemental analysis .

Q. Advanced: How can researchers design experiments to evaluate the cytotoxic efficacy of this compound derivatives against cancer cell lines, and what factors contribute to variability in IC₅₀ values?

Answer:
Cytotoxicity assays involve treating cancer cells (e.g., A-549 lung carcinoma) with this compound derivatives at varying concentrations (10–140 mg/mL) and using the MTT assay to measure cell viability after 24 hours . Advanced protocols include:

• Morphological analysis : Phase-contrast microscopy to observe apoptosis-related changes (e.g., cell shrinkage, detachment) .
• DAPI staining : Fluorescence microscopy to detect chromatin condensation and nuclear fragmentation .
  Variability in IC₅₀ values arises from structural factors:
• Monomeric vs. dimeric structures : Dimeric pyridinium bromides (e.g., m-xylene-linked derivatives) often show lower IC₅₀ (20 mg/mL) compared to flexible dimers (100 mg/mL) due to enhanced membrane interaction .
• Substituent effects : Electron-withdrawing groups (e.g., nitro) increase electrophilicity, enhancing cytotoxicity .

Q. Basic: What spectroscopic and thermal analysis techniques are critical for characterizing the structural and phase behavior of this compound compounds?

Answer:

• ¹H NMR : Resolves pyridinium ring protons (δ 8.5–9.5 ppm) and alkyl chain protons (δ 0.5–2.5 ppm) using deuterated DMSO .
• DSC (Differential Scanning Calorimetry) : Identifies phase transitions, such as solid-solid transitions in (bis)thiourea this compound at 150 K (first-order) and 180 K (second-order) .
• Dielectric spectroscopy : Measures ion dynamics and dielectric relaxation to study order-disorder transitions in crystalline phases .

Q. Advanced: In studying phase transitions in this compound complexes, how should dielectric spectroscopy data be interpreted alongside differential scanning calorimetry results?

Answer:
Dielectric spectroscopy reveals ion mobility changes during phase transitions. For example, in (bis)thiourea this compound:

• T₁ = 180 K (second-order transition) : Dielectric permittivity shows a gradual increase, correlating with DSC-detected latent heat absence .
• T₂ = 150 K (first-order transition) : A sharp permittivity drop indicates restricted ion motion due to structural ordering, confirmed by DSC enthalpy changes . Cross-referencing dielectric anomalies with DSC thermograms ensures accurate assignment of transition mechanisms.

Q. Basic: What are the best practices for ensuring reproducibility in the synthesis of this compound derivatives, particularly regarding purity and structural confirmation?

Answer:

• Purification : Recrystallization from ethanol/acetone mixtures removes unreacted alkyl bromides .
• Purity assessment : Melting point analysis (e.g., this compound perbromide melts at 188–190°C) and HPLC .
• Structural validation : ¹H/¹³C NMR, FT-IR (C-Br stretch at ~600 cm⁻¹), and comparison with literature data .
• Documentation : Detailed experimental protocols (solvent ratios, reaction times) as per Beilstein Journal of Organic Chemistry guidelines to enable replication .

Q. Advanced: What molecular docking approaches are employed to investigate the interaction mechanisms between this compound derivatives and biological targets?

Answer:

• Software : AutoDock Tools (ADT) and AutoDock Vina for docking studies .
• Protocol :
  • Optimize ligand geometry (e.g., this compound derivatives) using ChemDraw and Gaussian.
  • Prepare protein targets (e.g., EGFR kinase) by removing water molecules and adding polar hydrogens.
  • Use genetic algorithms to explore binding poses, with binding affinity calculated via the Lamarckian model .
• Validation : Compare docking scores (e.g., binding energy < −6 kcal/mol) with experimental IC₅₀ values to identify structure-activity relationships .

Q. Advanced: How are this compound derivatives utilized as additives in bromine-generating electrochemical cells, and what synthesis optimizations enhance their performance?

Answer:
Alkyl 3-methyl pyridinium bromides (e.g., 3-methyl-1-octylthis compound) act as bromine-complexing agents in Zn/Br₂ batteries, preventing bromine diffusion . Synthesis optimizations include:

• Alkyl chain tuning : Longer chains (C₁₀–C₁₈) improve bromine sequestration but may reduce ionic conductivity .
• Concentration : 0.5–1.0 M aqueous solutions achieve optimal electrolyte stability .
  Performance is evaluated via cyclic voltammetry and charge-discharge cycling .

Q. Basic: What safety protocols should be followed when handling this compound derivatives in laboratory settings?

Answer:

• Hazard mitigation : Use PPE (gloves, goggles) due to skin/eye irritation risks (R36/37/38) .
• Ventilation : Handle in fume hoods to avoid inhalation of fine powders .
• Storage : Keep in airtight containers away from oxidizers (e.g., dichromates) to prevent combustion .
• Waste disposal : Neutralize bromide residues with NaHCO₃ before aqueous disposal .

Comparison with Structurally Similar Compounds

Monomeric vs. Dimeric Pyridinium Bromides

Dimeric pyridinium bromides, such as m-xylene-linked or flexible aliphatic chain-linked derivatives, exhibit enhanced anticancer activity compared to monomeric forms. For example:

• Monomeric pyridinium bromide 3 (IC₅₀: 20 µg/mL) showed superior cytotoxicity against lung cancer cells (A-549) compared to dimeric analogs 1 and 2 (IC₅₀: 100 µg/mL) .
• Dimeric derivatives, however, demonstrate higher thermal stability and unique columnar phase behavior in ILCs due to increased molecular rigidity .

Table 1: Anticancer Activity of Mono- and Dimeric Pyridinium Bromides

Counterion Effects: Br⁻ vs. PF₆⁻

Replacing bromide with hexafluorophosphate (PF₆⁻) alters physicochemical properties:

• NMR Shifts : The protons near the pyridinium nitrogen in Br⁻ salts resonate at 9.17–9.24 ppm, while PF₆⁻ analogs show upfield shifts (8.47–8.62 ppm) due to weaker hydrogen bonding .
• Phase Transitions : PF₆⁻ salts exhibit lower transition temperatures to isotropic phases compared to Br⁻ derivatives, enhancing their utility in low-temperature ILC applications .

Table 2: Counterion Impact on Pyridinium Salts

Alkyl Chain-Length Variants

Alkyl chain length modulates micellar and biological properties:

• 1-Butylthis compound (C₄ chain): Used in micellization studies, with a critical micelle concentration (CMC) influenced by temperature and hydrophilic groups .
• Dodecylthis compound (C₁₂ chain): Demonstrates surfactant properties with a CMC of 0.8 mM, effective in corrosion inhibition for mild steel .
• Hexadecylthis compound (C₁₆ chain): Exhibits higher surface excess (Γ_max) due to stronger hydrophobic interactions .

Specialized Derivatives

• 1-(1-Adamantyl)this compound : A bulky adamantane-substituted derivative with a melting point of 245°C, used in organic synthesis and drug design .
• Pyridinium tribromide: A brominating agent for ketones and phenols, distinct from this compound due to its tribromide counterion (Br₃⁻) .

Key Research Findings

• Anticancer Mechanisms: Dimeric pyridinium bromides activate Ca²⁺ signaling pathways, while monomeric forms induce apoptosis via chromatin condensation .
• Corrosion Inhibition : this compound derivatives (C1–C3) achieve >90% inhibition efficiency for mild steel in acidic environments through adsorption .
• Synthetic Flexibility : Microwave-assisted synthesis enables solvent-free preparation of nitrobenzyl-substituted derivatives with high yields (~95%) .