Random Survey of Commercially Available Mosquito Repellents

Picaridin is a key active ingredient in commercial mosquito repellents, gaining popularity especially in safety-conscious and odourless markets in Europe and America. A random sample of 10 mosquito repellent products from various e-commerce sites across different countries/regions (see Table 1.) revealed that Picaridin accounts for 36% of effective mosquito-repelling ingredients; plant essential oils, such as citronella and lemon eucalyptus, follow at 20%; and DEET at 11%. The remainder consists of other effective ingredients, such as IR3535 and synthetic pyrethroids.

This compound, developed by Bayer in Germany, is colourless, odourless, and non-greasy. Its mosquito-repelling mechanism involves interfering with mosquitoes’ olfactory receptors, competitively inhibiting their perception of human odours (such as carbon dioxide and lactic acid), thereby blocking their ability to locate targets. DEET has long been the market-leading insect repellent. Beyond disrupting insects’ olfactory organs, its high-concentration formulations provide sustained blockage of their odour recognition capabilities.

In natural mosquito repellent products, the main active components of citronella oil include citronellal and citronellol, which primarily work by interfering with insects’ olfactory organs to form an odour barrier, possibly supplemented by mild neurotoxic effects. Lemon eucalyptus oil’s active ingredient, PMD (p-menthane-3,8-diol), also primarily exerts effects similar to Picaridin by disrupting olfactory organs.

History of Chinese Quwenling and PMD

In mainland China during the 1980s and 1990s, Quwenling was the primary effective mosquito-repelling ingredient. According to the paper¹, the distillation waste residue from extracting lemon eucalyptus oil (Eucalyptus maculata citriodon) can be processed further to produce PMD (p-menthane-3,8-diol, also known as PMD38).

Books² and the British company Citrepel confirm that PMD is the main component of Quwenling. At the same concentration, PMD offers shorter protection times than Picaridin and DEET³.

PMD can be obtained not only from lemon eucalyptus leaves but also through synthetic preparation. A Japanese company, Takasago, disclosed a process⁴ using (+)-citronellal for cyclisation to synthesise PMD. Further esterification of PMD with different acid anhydrides yields the corresponding diester derivatives⁵.

These diesters and monoesters can serve as cooling agents in daily chemical products such as shower gels and facial cleansers, providing mild TRPM8 activation effects.

Anhydride Type	Derivative Name	Type
Acetic anhydride	PMD diacetate	Diester
Propionic anhydride	PMD dipropionate	Diester
Valeric anhydride	PMD dipentanoate	Diester
Caproic anhydride	PMD dihexanoate	Diester
Various anhydrides	PMD monoester	Monoester
Table 2. Sorting of PMD derivatives.

Hydrogen Bonding “Grab and Stand”

Cooling agents, such as common menthol and WS-3, produce a cooling sensation in the human body by selectively stimulating TRPM8 receptors (cold receptors). PMD likewise generates a cooling feeling by activating TRPM8 receptors⁶. PMD features a p-menthane skeleton with two hydroxy (-OH) functional groups at positions 3 and 8. This chemical structure closely resembles menthol, which also has a p-menthane skeleton and a single hydroxy (-OH) group at position 3.

TRPM8 receptors exhibit a tetrameric structure⁷ composed of four identical subunits, each containing six transmembrane α-helices (S1-S6), where S5 and S6 form the ion channel and S1 to S4 create a three-dimensional hydrophobic binding pocket.

The p-menthane skeleton, a rigid six-membered ring structure, fits precisely into TRPM8’s hydrophobic cavity, much like a key entering a lock. At this point, menthol’s hydroxy (-OH) group forms a precise hydrogen bond with R842 within the hydrophobic cavity⁸, akin to the key’s teeth “grasping” the lock. Larger hydrophobic groups like the isopropyl moiety interact with other hydrophobic amino acids such as L843 and L846 in the cavity, “standing” at the pocket’s base to stabilise the molecule’s binding pose. This ingenious “grab and stand” mechanism activates the TRPM8 receptor.

Once the channel opens, cations such as calcium ions flood into the nerve cells, generating electrical signals that the brain interprets as a cooling sensation. PMD, sharing a similar chemical structure with menthol, achieves the same cooling effect via this mechanism. However, PMD’s additional hydroxy (-OH) group increases molecular polarity, theoretically affecting binding affinity to TRPM8 and secondary interactions with other amino acids, thus influencing activation efficiency. Cooling strength assessments indicate PMD’s cooling sensation is approximately 11% of menthol’s.

Yet, this extra hydroxy (-OH) group at position 8 in PMD is considered the key to its highly effective mosquito-repelling action—a biological mechanism entirely distinct from TRPM8 activation in humans. From the earlier summary of repellents, most work by masking human odours, forming a sufficient odour barrier on the skin surface.

PMD’s hydroxy (-OH) at position 8 first enhances molecular polarity. In the -OH group, oxygen’s electronegativity far exceeds hydrogen’s, pulling shared electrons towards itself and creating a partial negative charge (δ-) on oxygen and partial positive (δ+) on hydrogen. This charge separation renders the hydroxy group polar. When a PMD molecule’s positively charged hydrogen approaches another’s negatively charged oxygen, electrostatic attraction forms a hydrogen bond. With two -OH groups, one PMD molecule can form hydrogen bonds with other PMD molecules or skin-surface water/protein polar groups, anchoring firmly. In contrast, menthol’s single group forms only a chain. Thus, PMD’s dual -OH groups create intermolecular and skin-binding hydrogen bond networks, boosting adhesion.

Most insect-repelling substances are highly volatile, yielding short protection times. Research shows PMD has lower vapour pressure, linked to its hydroxy (-OH) groups⁹. Vapour pressure measures liquid volatility; higher values mean easier evaporation. Among intermolecular forces, hydrogen bonds are strongest, so PMD molecules—more polar—are tightly locked by these bonds. More hydroxy groups amplify this “glue” strength. Purely comparing hydroxy counts, PMD outlasts plant-derived repellents like citronellol (1) and geraniol (1) in protection time (synthetic Picaridin/DEET products often use emulsion slow-release formulations to extend efficacy).

WS-3 Cooling Agent: Traditional Structure and Mosquito-Repelling Potential

WS-3 represents a traditional and mature cooling agent within the WS family. Its cooling strength ranks around 150, placing it among the top in the series. As a menthol derivative, WS-3 shares the p-menthane skeleton with menthol and PMD, but features an ethylcarboxamide (-CONHCH₂CH₃) functional group at position 3. Interestingly, WS-3, alongside menthol and PMD, exhibits potential mosquito-repelling activity despite primarily serving as a cooling agent.

In the 1970s, Britain’s Wilkinson Sword initiated a research project to find menthol substitutes for improving shaving products. WS-3 emerged from this effort, offering a pure and persistent cooling sensation without menthol’s strong mint odour, bitterness, or high volatility. After WS-3’s patent expired, Givaudan built upon it to develop next-generation cooling agents.

Early traditional synthetic fragrance development relied on researchers’ experience¹⁰, following a “synthesize-taste-resynthesise” workflow. In 1951, Hensel and Zotterman hypothesised that menthol produces cooling by raising the activation threshold temperature of cold receptors^11、12; this gained molecular evidence after TRPM8’s discovery in 2002, spurring in vitro bioassay development¹³. Givaudan then combined bioassays with quantitative sensory methods, marking a paradigm shift in flavour ingredient discovery, as noted by organic chemistry head Andrew Daniher. Subsequently, around 450 menthol derivative substitutes were developed.

In 2006, Givaudan published a patent¹⁴ on mosquito repellents. During menthol substitute research, developers found p-menthane skeleton compounds not only activate TRPM8 receptors but also disrupt olfactory receptors in mosquitoes and German cockroaches for insect-repelling effects.

WS-3’s N-variants, such as N-substituted carbamates based on the p-menthane skeleton, resemble menthol and PMD but employ a carbamoyl structure to enhance hydrogen bond networks and reduce volatility via amide/ester groups. In 1993, Colgate-Palmolive disclosed a patent using branched fatty acid amides’ low volatility and strong interference for long-lasting mosquito repulsion¹⁵. This featured Neoalkanamides—special fatty amides with branched chains on both sides of the carbonyl (C=O)—typically N-mono- or N,N-disubstituted, with nitrogen-linked alkyl, aryl, or cycloalkyl groups. Their bulky, hydrophobic branched structures, combined with polar amide anchors, boost adhesion to skin or clothing, lower vapour pressure for sustained release, and outperform DEET in efficacy.

Givaudan’s researcher Markus Gautschi adapted this prior art, applying neoalkanamide’s branched amide principle to p-menthyl N-substituted carbamates on the p-menthane skeleton, achieving dual “cooling + repelling” effects. Here, the p-menthyl group replaces the neoalkane chain while retaining amide-like polar anchors and hydrogen bonding. N-group diversity in menthol-based variants like WS-3—such as N-aryl or N-cycloalkyl—yields larger molecular volumes and lower vapour pressure. The rigid p-menthane skeleton further enhances insect disruption.

Conclusion

From menthol to WS-3 and natural derivatives like PMD, cooling agents have not only revolutionised the sensory experience of personal care products but also unexpectedly pioneered new mosquito-repelling applications. The shared p-menthane skeleton enables these compounds to activate TRPM8 receptors for persistent cooling sensations while forming effective odour barriers that disrupt mosquitoes’ olfactory perception.

Companies like Givaudan have transformed traditional expertise into efficient innovations through bio-directed research, developing odourless, low-volatility alternatives that meet consumers’ dual demands for comfort and safety.

Skin Vape Mist	Icaridin/Picaridin	Japan
KINCHO Mosquito Gone Spray	Pyrethroids	Japan
Earth Saratect Mist RICH30	Icaridin/Picaridin	Japan
Skin Vape Premium Baby Gel	Icaridin	Japan
Skin Vape Mist Alcohol Free	Icaridin	Japan
Saratect Unscented Spray	Picaridin	Japan
PreShower DF Mist	Picaridin	Japan
Skin Vape Mist Two-Pack	Picaridin	Japan
Saratect Sheet	Picaridin	Japan
Earth Mosquito Spray	Botanical oils	Japan
Proven Insect Repellent Spray	Picaridin	USA
Cutter Backwoods Insect Repellent	DEET	USA
Coleman SkinSmart DEET-Free	IR3535	USA
Cliganic Natural Repellent Bracelet	Citronella and essential oils	USA
Summit Mosquito Dunks	BTI (Bacillus thuringiensis israelensis)	USA
GOOTOP Outdoor Mosquito Lamp	No chemical, physical light trap	USA
OFF! Deep Woods	DEET	USA
Repel Lemon Eucalyptus	Lemon eucalyptus oil	USA
Thermacell E-Series	Picaridin	USA
SkinSmart DEET-Free Spray	IR3535	USA
Chaowei Green Bottle	Picaridin	China
Lanju Electric Mosquito Liquid	Prallethrin	China
Runben Child Mosquito Spray	Botanical oils (citronella, lavender)	China
Florida Water (Liushen, Baique Ling)	Citronella, osmanthus	China
Lanju Mosquito Coil Liquid	Prallethrin	China
Chaowei Mosquito Liquid	Picaridin	China
Chaowei Electric Mosquito Mat	Prallethrin	China
Lanju Baby Mosquito Patch	Botanical citronella	China
Ice Piece Mosquito Balm	Borneol, menthol	China
Japan Ding Ding Mosquito Spray (Guangdong)	Ethyl butylacetylaminopropionate	China
Cinq sur cinq Spray	IR3535	France/Europe
Autan Protection Plus	Picaridin	France/Europe
Insect Ecran Zones Infestées	DEET	France/Europe
Puressentiel Anti-Pique Spray	Botanical oils (lemon eucalyptus)	France/Europe
NeoBulle Anti-Moustique	Botanical oils	France/Europe
Moustifluid Spray	DEET	France/Europe
Nexa Lotte Electric Mosquito Liquid	Prallethrin	Germany/Europe
Germany Shield Spray	Picaridin/botanical	Germany/Europe
Apaisyl Mosquito Repellent Spray	IR3535	Europe
RAID Night & Day	Picaridin/Synthetic pyrethroids	Europe
Nature’s Repellent	Citronella/botanical	Singapore
Biogents BG-Mosquitaire Trap	No chemicals, physical trap	Germany
SANO Mosquito Repellent Spray	DEET	Israel
Thermacell Portable Mosquito Repeller	Picaridin	Australia
PowerPac Mosquito Repellent Spray	Picaridin	Malaysia
Dabur Odomos Cream	Botanical oils (lemon eucalyptus)	India
Mortein Liquid	Synthetic pyrethroids	UK/Global
Godrej Goodknight Fabric Roll-On	Botanical oils	India
3M Ultrathon Insect Repellent	DEET	USA/Global
Xiaomi Smart Mosquito Device	Picaridin/synthetic pyrethroids	Multiple/Global
Table 1. The random sample of 10 mosquito repellent products from various e-commerce sites across different countries/regions. ©Foreverest & supported by Grok.
Product Name	Active Ingredient(s)	Country/Region

References

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2. Insect Repellents: Principles, Methods, and Uses, Mustapha Debboun et al,.
3. EFFICACY OF INSECTREPELLENTS CURRENTLYAVAILABLE IN NEW ZEALAND, 2017
4. Method for producing para-menthane-3,8-diol, US5959161A
5. Solvent-free synthesis of novel para-menthane-3,8-diol ester derivatives from citronellal using a polymer-supported scandium triflate catalyst, Lubabalo Mafu et al,. 2016
6. Characterization of the mouse cold-menthol receptor TRPM8 and vanilloid receptor type-1 VR1 using a fluorometric imaging plate reader (FLIPR) assay, H-J Behrendt et al,. 2004
7. Structural modeling of selectivity filter in transient receptor pontential melastatin 8 ion channel, Lizhen Xu et al,. 2019
8. Molecular mechanisms underlying menthol binding and activation of TRPM8 ion channel, Lizhen Xu et al,. 2020
9. Advances in mosquito repellents: effectiveness of citronellal derivatives in laboratory and field trials, Immacolata Iovinella et al,. 2022
10. Industrial Fragrance Chemistry: A Brief Historical Perspective, Dr. Olivier R. P. David, 2023
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14. Patent US20060063764A1, Markus Gautschi, 2003
15. Patent US5182305A, Robert J. Steltenkamp, 1991
16.