N-Vinyl-2-pyrrolidone

Synthetic Routes and Reaction Conditions: N-Vinyl-2-pyrrolidone is synthesized through the vinylation of 2-pyrrolidone. The process involves the base-catalyzed reaction of 2-pyrrolidone with acetylene. The reaction typically occurs under controlled conditions to ensure high yield and purity .

Industrial Production Methods: Industrial production of this compound involves several steps:

Synthesis of 2-pyrrolidone: This is achieved by treating γ-butyrolactone with ammonia.

Vinylation: The 2-pyrrolidone is then reacted with acetylene in the presence of a base catalyst to introduce the vinyl group.

Types of Reactions: N-Vinyl-2-pyrrolidone undergoes various chemical reactions, including:

Polymerization: It readily polymerizes to form polyvinylpyrrolidone.

Hydrolysis: It can hydrolyze under acidic or basic conditions.

Radical Reactions: It participates in radical polymerization reactions.

Common Reagents and Conditions:

Polymerization: Initiated by radical initiators such as azobisisobutyronitrile (AIBN).

Hydrolysis: Conducted in the presence of acids or bases.

Major Products:

Polyvinylpyrrolidone: The primary product formed through polymerization.

Hydrolyzed derivatives: Formed through hydrolysis reactions.

Plastics and Coatings

NVP is extensively used in the formulation of plastics and coatings, particularly in UV-curable systems. Its incorporation enhances the mechanical properties of films, making them flexible yet durable. Key applications include:

• UV-Curable Coatings : NVP improves the elongation and viscosity of coatings used in various industries, including medical radiation formulations and wood coatings .
• Wood Industry : It enhances the performance of UV-resistant coatings for wooden flooring, providing physical characteristics similar to waxless flooring .

Biomedical Applications

NVP has shown significant promise in biomedical fields, particularly in drug delivery systems and tissue preservation. Notable uses include:

• Drug Delivery Systems : NVP-based hydrogels exhibit thermoresponsive behavior, making them suitable for controlled drug release applications. These hydrogels can respond to physiological temperature changes to release drugs effectively .
• Embalming Solutions : As an alternative to traditional formalin solutions, NVP has been used for embalming cadavers for medical education. It maintains the elasticity of soft tissues, providing a more realistic surgical training environment .

Material Science

NVP's role extends into material science where it is utilized in synthesizing various polymeric materials:

• Hydrogels : NVP copolymers are synthesized with other monomers to create hydrogels that can be tailored for specific applications like wound dressings and tissue engineering .
• Nanoparticles : The use of NVP in creating mesoporous nanoparticles has been explored for sensitive fingerprint detection, showcasing its versatility in forensic science .

Case Study 1: Controlled Drug Delivery Using NVP-Based Hydrogels

In a study examining poly(N-isopropylacrylamide-co-N-vinyl-2-pyrrolidone) hydrogels, researchers found that varying the NVP content influenced the swelling behavior and drug release kinetics significantly. The study concluded that these hydrogels could serve as effective intelligent drug carriers due to their responsiveness to temperature changes .

Case Study 2: Embalming Efficacy of this compound

A comparative study on embalming techniques highlighted the effectiveness of NVP over traditional methods. The results indicated that cadavers treated with NVP maintained tissue characteristics closer to living conditions compared to those treated with formalin, thus enhancing surgical training outcomes .

The mechanism of action of N-Vinyl-2-pyrrolidone primarily involves its ability to undergo polymerization and form polyvinylpyrrolidone. This polymer interacts with various molecular targets and pathways, enhancing the solubility and stability of active compounds in drug delivery systems. It also acts as a stabilizer in aqueous dispersions, improving the bioavailability of poorly soluble compounds .

Physical and Chemical Properties

• NVP vs. Vinyl acetate : While NVP forms hydrophilic polymers, vinyl acetate yields polyvinyl acetate (PVAc), which is hydrophobic and used in adhesives and paints. PVAc-based biopolyesters exhibit higher tensile strength (e.g., 94 MPa) compared to NVP-based systems (70 MPa) due to increased crosslinking density .
• NVP vs. It lacks polymerizable vinyl groups and is primarily used in industrial applications requiring high solvency power .

Polymerization Behavior and Copolymer Performance

• NVP Copolymers : Amphiphilic copolymers of NVP and allyl glycidyl ether form micelles capable of co-delivering hydrophobic (paclitaxel) and hydrophilic (doxorubicin) drugs. These copolymers exhibit distinct ¹³C NMR signals at 176.65 ppm (carboxylate end groups) and IR bands at 1049.5 cm⁻¹ (ether C-O-C stretching), enabling precise structural characterization .
• Comparison with Acrylamide : Acrylamide-based polymers are neurotoxic and less suitable for biomedical applications. NVP’s low toxicity and biocompatibility make it preferable for drug delivery and hydrogels .

Application-Specific Performance

• Drug Release : NVP-based telomers with carboxyl end groups show controlled doxorubicin release, achieving 80% release over 5 hours via dialysis (500 Da MWCO membrane). In contrast, unencapsulated doxorubicin releases >90% within 2 hours under similar conditions .
• Hydrogel Formation : NVP-glycidyl methacrylate hydrogels exhibit a 3.26-fold mass increase upon swelling, suitable for wound dressings. Comparatively, polyethylene glycol diacrylate hydrogels swell more rapidly but lack NVP’s adhesive properties .
• Antimicrobial Coatings: NVP polymers grafted onto polypropylene membranes via ATRP demonstrate superior antifouling performance compared to acrylate-based coatings, attributed to PVP’s hydrophilicity and non-ionic character .

Research Findings and Data Tables

Table 1: Mechanical Properties of NVP vs. Vinyl Acetate Biopolyesters

Source: Comparative study of maleic anhydride-modified biopolyesters

Table 2: Drug Release Kinetics of NVP Copolymers

Source: Dialysis membrane (500 Da MWCO) study

N-Vinyl-2-pyrrolidone (NVP) is a compound that has garnered attention for its diverse biological activities, particularly in the fields of biomedicine and material science. This article presents a comprehensive overview of the biological activity of NVP, highlighting its mechanisms of action, potential therapeutic applications, and safety considerations based on various research findings.

NVP exhibits several biological activities primarily through its interactions with cellular pathways and proteins. One significant mechanism involves its role as a bromodomain inhibitor. Research indicates that NVP can inhibit the binding of bromodomain-containing proteins, which are crucial for regulating gene expression related to inflammation and cell differentiation .

Osteogenic Effects

A notable study demonstrated that NVP enhances bone morphogenetic protein 2 (BMP2)-induced osteoblast differentiation in C2C12 cells. The presence of NVP led to a dose-dependent increase in alkaline phosphatase (ALP) activity, a marker for osteoblast differentiation. Specifically, co-treatment with 5 mM NVP and 100 ng/mL BMP2 produced effects comparable to higher concentrations of BMP2 alone, indicating that NVP amplifies the responsiveness of these cells to BMP2 .

In vivo studies using rabbit calvarial defect models further supported these findings. Histomorphometric analysis revealed that NVP-loaded poly(lactic-co-glycolic acid) (PLGA) membranes resulted in significantly greater bone regeneration compared to unloaded membranes. This suggests that NVP may serve as an "osteopromotive substance," potentially beneficial in treating conditions associated with bone loss, such as osteoporosis .

Immune Modulation

NVP has also been explored for its immunomodulatory properties. In a study examining its adjuvant activity, peptide-polymer complexes containing NVP were shown to activate the immune system effectively, leading to enhanced antigen-specific immune responses . This property highlights NVP's potential utility in vaccine formulations and immune therapies.

Summary of Research Findings

The following table summarizes key research findings related to the biological activity and safety profile of this compound:

Basic Research Questions

Q. What are the primary synthesis routes for NVP, and how do reaction conditions influence yield and purity?

NVP is synthesized via two main pathways:

• Pathway 1 : Reaction of γ-butyrolactone with ammonia to form 2-pyrrolidone, followed by pressurized acetylene addition .
• Pathway 2 : Reaction of γ-butyrolactone with monoethanolamine to produce N-hydroxyethylpyrrolidone, which undergoes vapor-phase dehydration .

A green chemistry alternative involves catalytic condensation of biogenic acids (e.g., levulinic acid) to form NVP precursors, minimizing side-products like 2-pyrrolidone through optimized Na₂O/SiO₂ catalyst ratios . Yield and purity depend on temperature, catalyst selection, and inhibition of side reactions (e.g., C–N bond cleavage).

Q. Which analytical techniques are most effective for quantifying trace NVP in pharmaceutical formulations?

• Headspace Solid-Phase Microextraction (HS-SPME) : Polypyrrole-coated fibers selectively extract NVP from drug matrices, achieving detection limits of 0.1–0.5 µg/mL when paired with gas chromatography and nitrogen-phosphorous detection (GC-NPD) .
• High-Performance Liquid Chromatography (HPLC) : Validated for quantifying residual NVP in polymerized products (e.g., PVP) using UV detection at 210 nm .

Q. How can crystallization techniques improve NVP purity, and what challenges arise during scale-up?

NVP is typically purified via fractional distillation, but crystallization offers higher purity (>99.5%) by selectively removing oligomers and acetylene derivatives. Key parameters include:

• Solvent selection (e.g., toluene or cyclohexane) to optimize crystal growth.
• Cooling rates to prevent amorphous phase formation .
  Challenges include maintaining consistent supersaturation levels in industrial-scale reactors and avoiding inhibitor degradation (e.g., phenolic antioxidants).

Advanced Research Questions

Q. How do copolymerization kinetics with NVP affect material properties in biomedical applications?

NVP copolymerizes with monomers like acrylic acid or vinylpyridine via free-radical mechanisms. Reactivity ratios (e.g., r₁ for NVP = 0.45, r₂ for 4-vinylpyridine = 1.2) determine block vs. random structures, influencing hydrophilicity and drug-loading capacity . Advanced characterization includes:

• NMR Spectroscopy : To quantify monomer sequence distribution.
• Differential Scanning Calorimetry (DSC) : To assess glass transition temperature (Tg) shifts caused by crosslinking .

Q. What methodological approaches resolve contradictions in NVP toxicity data across studies?

While IARC classifies NVP as Group 3 (not carcinogenic to humans), rodent studies report nasal adenomas at high inhalation doses (≥50 ppm). To reconcile discrepancies:

• Dose-Response Analysis : Compare tumor incidence at varying exposure levels (e.g., 10 ppm vs. 50 ppm) .
• Metabolite Profiling : Identify species-specific detoxification pathways (e.g., urinary excretion of NVP metabolites in rats vs. humans) .
• Epigenetic Studies : Assess DNA methylation changes in exposed cell lines to differentiate genotoxic vs. non-genotoxic mechanisms .

Q. How can starch-NVP polymer blends enhance biodegradable film performance for food packaging?

Blending thermoplastic starch (TPS) with poly(N-vinyl-2-pyrrolidone) (PVP) improves:

• Mechanical Strength : PVP increases tensile strength by 40% at 20% w/w loading due to hydrogen bonding with starch hydroxyl groups .
• Barrier Properties : Reduced water vapor permeability (25% decrease) via PVP’s hydrophobic domains .
  Methodology includes solvent casting with glycerol plasticizer and FTIR analysis to confirm hydrogen-bond interactions.

Q. Data Contradiction Analysis

Q. Why do some studies report NVP’s carcinogenicity in rodents while others classify it as safe?

Discrepancies arise from:

• Exposure Routes : Inhalation studies show nasal tumors, while oral/dermal studies lack significant findings .
• Species Sensitivity : Rodent olfactory epithelium is more susceptible to NVP-induced hyperplasia than primates .
• Study Duration : Short-term assays (≤12 months) may miss latent tumorigenic effects .

Resolution : Conduct longitudinal studies with multiple exposure routes and integrate histopathology data from OECD-compliant protocols.

Q. Safety and Handling Protocols

Q. What safety measures are critical for handling NVP in laboratory settings?

• Ventilation : Use fume hoods to maintain airborne concentrations below 1 mg/m³ (Russian occupational limit) .
• Personal Protective Equipment (PPE) : Nitrile gloves and safety goggles to prevent dermal/ocular exposure .
• Waste Disposal : Neutralize residual NVP with alkaline solutions (pH >10) before incineration .