Wilkinson Sword Cooling Compounds:
From the Beginning to Now
A chronological review of research into the cooling and therapeutic effects of these types
of materials.
John Leffingwell, Leffingwell & Associates, and David Rowsell, Chromatography Resources
Wilkinson Sword was founded in 1772, and its origins began with the manufacture of swords and, later, guns and shears. In 1898, the company branched
out to manufacture safety razors and became a U.K.-leader in
shaving products. In the 1960s, it introduced stainless steel razor
blades coated with PTFE (polytetrafluoroethylene), which in
1967 brought one of the present authors (David Rowsell) to the
company. With a background in fluorine chemistry, the author’s
project at the time was to investigate PTFE alternatives.
Late 1960s to the 1980s: Pursuing New Compounds
However, around 1969–1970, Wilkinson Sword management
wanted to expand/diversify and proposed products in the toi-letries/cosmetics area, and thus the R&D focus shifted. This
proposal was developed further (mostly by Wilkinson Sword
researcher Hugh Watson) into pursuing compounds with a
menthol-like cooling effect, no odor and low volatility. This
idea was attractive because one of the major negatives of men-thol-containing shaving creams and after-shave lotions was the
propensity for eye and mucus membrane irritation. A literature
search indicated that these compounds were likely to be novel.
The only cooling compounds other than menthol known at that
time seemed to owe their properties to hydrolysis to menthol.
It appeared from published physiological studies that the
interaction of menthol with “cold receptors” in the skin could be
interpreted as a drug-receptor type of interaction. A structure-activity relationship (SAR) approach using the methodology
introduced by Hansch et al. in the mid-1960s was applied. 1–7
General principles that were developed based on correlations
observed in work on acetylcholine drug-receptor interactions
were applied in addition to SAR methods. 8
As a result of preparing a few compounds (early WS numbers,
e.g. WS- 3), it seemed likely that compounds with cooling properties and low volatility could be prepared. More staff was
recruited, and the project began. The work expanded from
1971 onwards, with about 1,200 cooling compounds being
synthesized. 9–40
In the course of the work, it was found that four important
criteria needed to be satisfied for a compound to possess effective cooling activity: 9
•;a;hydrogen;bonding;group
•;a;compact;hydrocarbon;skeleton
•;a;correct;hydrophilic/hydrophobic;balance;(LogP;between
1. 5–5.0)
•;a;molecular;weight;in;the;range;of;150–350
A hydrogen-bonding function appears essential for cooling
action. This is an electron-donating oxygen atom capable of
acting as a hydrogen bond acceptor. The best H-bonding groups
found were those of the oxygen groups of hydroxy, N-alkyl
carboxamides, sulfoxides and phosphine oxides.
For cooling activity, the hydrocarbon portion (or portions) of
the molecule must provide a compact hydrophobic region near
the site of hydrogen bonding. At the time of this early work,
researchers;did;not;have;access;to;the;numerous;LogP;calculators
available today in programs such as Chemsketch, ChemAxon,
ChemDraw or EpiSuite or, on the internet, via ChemSpider
or;the;Virtual;Computational;Chemistry;Laboratory;websites.
At the time of the research discussed here, the logP values of
cooling compounds were all hand-calculated using the published
tables of Hansch for the substituent p values. 5
Generally, strong cooling compounds had logP values in
the relatively narrow range of 1. 5–4.0, and values for nearly all
cooling compounds lay in the range of 1.0– 5.0. The calculated
logP value of (-)-menthol is 3.0±0.35, while experimental values
are 3. 2–3. 4.
Problems were encountered in deciding on a value for the
phosphine oxide group. At that time, there were very few measurements of logP of phosphine oxides. It was concluded that the
phosphine oxide group should be “balanced” by 14–15 carbon
atoms (compared to 10–11 in menthol and 12–13 with amides).
This was born out as a number of phosphine oxides were found
to be about three times cooler than (-)-menthol, based on cooling
threshold tests—e.g., isobutyl-sec-butyl-n-heptylphosphine
F- 1. The phosphine oxide group is capable of strong
H-bonding (via oxygen); the usual resonance description
of this bond is shown here
