The History and Development of Quantitative Structure-Activity Relationships (QSARs): Addendum

The History and Development of Quantitative Structure-Activity Relationships (QSARs): Addendum

John C. Dearden (School of Pharmacy & Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK)
DOI: 10.4018/IJQSPR.2017070104
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Following the publication of the history and development of QSAR, it became apparent that a number of matters had not been covered. This addendum is an attempt to rectify that. A very early approach (ca. 60 B.C.) by Lucretius shows that he understood how molecular size and complexity affect liquid viscosity. Comments by Kant (1724-1804) emphasized the necessity of mathematics in science. A claim that the work of von Bibra and Harless in 1847 pre-dated that of Overton and H.H. Meyer is shown not to be correct. K.H. Meyer and Gottlieb-Billroth published in 1920 what is probably the first QSAR equation. Brown, who with his co-author Fraser is credited with the first definitive recognition in 1868-9 that biological activity is a function of molecular structure, is often cited as Crum Brown; in fact, Crum was his second given name. The QSAR work of the Soviet chemist N.V. Lazarev in the 1940s was far ahead of his time, showing numerous correlations of biological activities and physicochemical properties with molecular descriptors. The subject of inverse QSAR is discussed.
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The author’s recent paper on the history and development of QSAR (Dearden, 2016) is a (relatively) concise coverage of the subject. With such a broad topic, it was almost inevitable that some important aspects were missed. Several people have contacted the author since his paper was published, to remind him of some of those omissions. The opportunity has also been taken to add more researches on the subject. Each topic treated here should be considered as an addition to one of the sections in the original paper (Dearden, 2016).


Lucretius (Titus Lucretius Carus) was a Roman poet and philosopher who lived ca. 99-55 B.C. His only known work is De Rerum Natura (On the Nature of Things) (Leonard, 1916). In Book II, Section “Atomic Forms and Their Combinations”, he wrote:

We see how quickly through a colander

The wines will flow; how, on the other hand,

The sluggish olive-oil delays: no doubt,

Because 'tis wrought of elements more large,

Or else more crook'd and intertangled.

So he was saying that liquid viscosity (η) was a function of molecular size and/or molecular complexity (involving, perhaps, shape, rotatable bonds, and intermolecular interactions). In the terminology of Brown and Fraser (1868-1869):

η = f(molecular size, molecular complexity) (1)

This was a very perspicacious observation and deduction for someone writing well over 2000 years ago. Whilst it would be stretching presumption too far to claim that Lucretius’s words represent the first published intimation of QSAR, there can be little doubt that his thinking was along those lines.

This topic relates to the section entitled “THE BEGINNINGS OF CORRELATION: Other Physicochemical Properties” in the original paper on the history and development of QSAR (Dearden, 2016).


In his paper on the history and development of QSAR (Dearden, 2016), the author quoted a number of great names from the past, the first of whom was Leonardo da Vinci (1452-1519), concerning the necessity of mathematics in chemistry. In addition to those, the philosopher Immanuel Kant (1724-1804) deserves mention. Friedman (2013), in his book on Kant, quoted him as saying that “in any special doctrine of nature, there can be only as much proper science as there is mathematics to be found therein”. Friedman points out that Kant went on to argue that chemistry (unlike pure physics or the mathematical theory of motion) would “only with great difficulty” ever become a proper science.

This topic relates to the section entitled “Early Approaches” in the original paper on the history and development of QSAR (Dearden, 2016).

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