Green Chemistry Revolution

Harnessing Nature's Medicine Cabinet with Deep Eutectic Solvents

Discover how innovative extraction techniques and advanced analytics are transforming natural product research

The Ancient Healing Power of Plants Meets Modern Science

For thousands of years, humans have turned to nature's pharmacy for healing. From Traditional Chinese Medicine to Ayurvedic practices, medicinal plants have formed the foundation of healthcare systems across civilizations. Even today, approximately 85% of essential botanical materia medica in traditional medical systems worldwide originate from plants, and the global botanical medicine sector exceeds $100 billion in market value4 .

These plants contain powerful bioactive compounds—chemical substances that can interact with our biological systems to produce therapeutic effects. From the aspirin derived from willow bark to the cancer-fighting paclitaxel from the Pacific yew tree, plant-based compounds continue to form the cornerstone of modern pharmacology.

Plant-Based Medicine Today

The continued relevance of plant-derived compounds in modern medicine underscores the importance of sustainable extraction methods.

Despite their proven value, unlocking these natural treasures has traditionally come with significant environmental costs. Conventional extraction methods have relied on petroleum-based solvents that are harmful to both ecosystem and human health. The quest for greener alternatives has led scientists to a breakthrough discovery: Deep Eutectic Solvents (DES).

Deep Eutectic Solvents: Nature-Inspired Liquid Gold

What Exactly Are Deep Eutectic Solvents?

Deep Eutectic Solvents represent a novel class of environmentally friendly solvents that have gained significant scientific attention since their discovery in the early 2000s. The first DES was a simple mixture of choline chloride (a vitamin-like compound) and urea in a 1:2 ratio, which combined to form a transparent liquid with a remarkably low melting point of 12°C—much lower than either component individually3 .

The term "eutectic" comes from the Greek word "eutēktos," meaning "easily melted," and describes a mixture that displays a melting point lower than that of any of its individual components. The "deep" designation indicates an unusually significant depression of this melting point, resulting from strong molecular interactions between the components3 .

DES Formation Process
Hydrogen Bond Acceptor (HBA)

Compounds like choline chloride, betaine, or amino acids

Hydrogen Bond Donor (HBD)

Compounds like urea, citric acid, malic acid, glycerol, or sugars

Mixing & Heating

Components mixed in specific ratios with mild heating

DES Formation

Extensive hydrogen bonding creates stable liquid at room temperature

Why DES Are Revolutionizing Green Extraction

Low Toxicity

Most DES components are natural compounds, making them environmentally friendly3 .

100% Atom Economy

Simple preparation generates no waste byproducts3 6 .

Tailorable Properties

DES can be "designed" with specific properties for different compounds3 .

Thermal Stability

DES remain stable at high temperatures with low volatility6 .

Common Components of Deep Eutectic Solvents
Component Type Examples Role Natural Source
Hydrogen Bond Acceptors (HBA) Choline chloride, Betaine, Amino acids Forms the ionic character of DES Eggs, beans, grains, shellfish
Hydrogen Bond Donors (HBD) Urea, Citric acid, Malic acid, Glycerol, Sugars Interacts with HBA through hydrogen bonding Various fruits, fermented foods, plant oils
Natural DES Components Primary metabolites like choline derivatives, amino acids, sugars, organic acids Creates natural deep eutectic solvents (NADES) All living organisms

A Closer Look at a Key Experiment

Identifying Bioactive Compounds from Traditional Remedies

To understand how DES extraction works in practice, let's examine a groundbreaking experiment that combined DES with advanced analytical techniques to identify bioactive compounds from plants traditionally used to treat snakebites2 .

Methodology: A Step-by-Step Approach

Researchers prepared several choline chloride-based DES with different hydrogen bond donors, including glycerol, urea, and malic acid. The components were mixed in specific molar ratios and heated at 80°C until a homogeneous liquid formed.

Twenty-two different plant species traditionally used as snakebite antidotes were collected, dried, and ground into fine powder to increase surface area for extraction.

Each plant powder was combined with the different DES systems and subjected to ultrasound-assisted extraction. The ultrasonic waves created cavitation bubbles that imploded near the plant cells, effectively breaking down cell walls and facilitating the release of bioactive compounds into the DES.

The extracts were tested for their ability to inhibit hyaluronidase, an enzyme that contributes to tissue destruction in snakebites. This was done using microplate-based bioassays.

Active extracts underwent further analysis using HPLC-HRMS-SPE-NMR—an advanced combination of separation and identification technologies. This system first separated complex mixtures through High-Performance Liquid Chromatography (HPLC), then analyzed compounds using High-Resolution Mass Spectrometry (HRMS) to determine molecular formulas. Next, compounds were trapped on Solid-Phase Extraction (SPE) cartridges and finally introduced into Nuclear Magnetic Resonance (NMR) spectrometers for detailed structural analysis2 .
Experiment Results

The experiment yielded fascinating results. While many active extracts contained tannins (known to neutralize snake venom), four plant extracts exhibited significant hyaluronidase inhibition from non-tannin compounds.

Through the HPLC-HRMS-SPE-NMR workflow, researchers identified specific flavonoids and alkaloids responsible for this activity.

Bioactive Compounds Identified Through DES Extraction

Compound Name Plant Source Bioactivity Potential Applications
Ansiumamide B Clausena excavata Hyaluronidase inhibition Snakebite treatment, Anti-inflammatory drugs
Myricetin 3-O-β-D-glucopyranoside Androsace umbellata Hyaluronidase inhibition Anti-venom development, Cosmeceuticals
Vitexin Oxalis corniculata Hyaluronidase inhibition Wound healing, Skincare products
Baicalein Scutellaria baicalensis α-Glucosidase inhibition Diabetes management
Chamanetin Uvaria chamae Fungal plasma membrane H+-ATPase inhibition Antifungal medications

Advanced Analytical Techniques

Illuminating Nature's Chemical Complexity

The Power of Hyphenated Techniques

The most significant advancement in phytochemical analysis has been the development of hyphenated techniques that combine multiple analytical methods into integrated systems. The HPLC-HRMS-SPE-NMR platform represents the cutting edge of this approach2 .

HPLC-HRMS-SPE-NMR Workflow

HPLC
Separation

HRMS
Mass Analysis

SPE
Extraction

NMR
Structure

This integrated approach allows researchers to identify novel compounds without the need for time-consuming isolation and purification steps that were previously necessary.

Other Essential Analytical Tools

UV-DAD Detection

Provides information about chromophores in molecules, helping to classify compounds like flavonoids that have characteristic UV absorption patterns2 .

TLC Bioautography

A simple but effective method that combines separation on a plate with biological activity screening. Particularly useful for quickly identifying antimicrobial compounds9 .

FTIR Spectroscopy

Reveals information about functional groups present in compounds, complementing data from other techniques9 .

Automated Systems

Modern analytical platforms integrate multiple techniques for high-throughput analysis of complex plant extracts.

Analytical Breakthrough

The integration of multiple analytical techniques into hyphenated systems has dramatically accelerated the pace of natural product discovery, allowing researchers to identify novel bioactive compounds with unprecedented speed and accuracy.

The Future of Plant-Based Medicine

Sustainable, Personalized, and High-Tech

Sustainability & Ethics

The plant extract industry is increasingly focusing on sustainable practices, including organic farming, fair trade partnerships, and carbon-neutral extraction processes5 .

Companies are investing in blockchain technology to ensure supply chain transparency and verify ethical sourcing of botanical materials5 .

Trending

Personalized Medicine

Advances in AI-powered health assessments and genetic profiling are enabling the development of customized plant-based supplements tailored to individual nutritional needs and wellness goals5 .

This personalized approach represents a return to the roots of traditional medicine, enhanced with modern technology.

Innovation

Advanced Technologies

While DES already represent a significant improvement, researchers continue to develop even more efficient methods.

Supercritical CO₂ extraction, biotech fermentation, and high-pressure homogenization are among the innovative techniques being combined with DES to further improve efficiency and sustainability6 .

Research

Market Growth and Applications

The global plant extracts market is projected to grow from USD 28.1 billion in 2025 to USD 63.1 billion by 2034, driven by increasing consumer preference for natural ingredients in food, beverages, pharmaceuticals, and cosmetics5 .

This growth is particularly strong in adaptogenic botanicals like ashwagandha, ginseng, and rhodiola for stress management, as well as immune-boosting supplements that gained prominence during the COVID-19 pandemic5 .

Food & Beverages
Pharmaceuticals
Cosmetics
Supplements

A Green Renaissance in Natural Product Research

The marriage of deep eutectic solvents with advanced analytical techniques represents a paradigm shift in how we explore and utilize nature's chemical bounty. These innovative approaches allow us to uncover novel bioactive compounds with greater efficiency and lower environmental impact than ever before.

As we face global challenges like antimicrobial resistance, chronic diseases, and climate change, the sustainable extraction and precise characterization of plant-based medicines offer promising solutions.

The ongoing revolution in green extraction technologies aligns with a broader movement toward sustainable and personalized healthcare. By combining ancient wisdom with cutting-edge science, researchers are opening new frontiers in drug discovery, functional foods, and natural products—ensuring that nature's pharmacy continues to provide healing and health for generations to come.

ISYDES 2025 - Bari, Italy

References