Optimization of Physicochemical and Biophysical Properties of

12 Optimization of Physicochemical and Biophysical Properties of Pesticides I. J. GRAHAM-BRYCE

Downloaded by FUDAN UNIV on February 12, 2017 | http://pubs.acs.org Publication Date: June 26, 1984 | doi: 10.1021/bk-1984-0255.ch012

East Malling Research Station, East Malling, Maidstone, Kent, England Pesticide performance depends on the intrinsic toxicity of the chemical concerned and on the amounts which reach the sites of toxic action. There is substantial scope for improving selection of candidate compounds for development and increasing efficiency of utilisation by optimising physico-chemical and biophysical properties which underlie these determinants of performance. This is illustrated by considering the dynamics of toxicant behaviour within receiving organisms and delivery of the toxicant from the point of application to the recipient. Analysis of the free energy relationships describing processes within the organism demonstrates the dangers of misinterpreting data on relative toxicity of different compounds and the importance of designing appropriate tests for comparing compounds. In considering delivery to the receiving organism it is now possible to define the optimum physico-chemical properties for many crop protection purposes. Much can also now be done to predict molecular structures which give these properties on the basis of partition relationships and knowledge of additive molecular characteristics such as paraquat. These principles are illustrated with specific examples. There are compelling reasons f o r seeking to optimise p e s t i c i d e p r o p e r t i e s i n r e l a t i o n to s e v e r a l c r i t e r i a , i n c l u d i n g s e l e c t i v e activity against the target organism, cost effectiveness, reliability against the target organism and avoidance of harmful e f f e c t s i n the environment. A common o b j e c t i v e i s to achieve the greatest degree of t o x i c e f f e c t to the intended r e c i p i e n t with the smallest amount o f chemical : o p t i m i s a t i o n of 0097-6156/ 84/ 0 2 5 5 - 0 1 8 5 5 0 6 . 7 5 / 0 © 1984 A m e r i c a n C h e m i c a l S o c i e t y

Magee et al.; Pesticide Synthesis Through Rational Approaches ACS Symposium Series; American Chemical Society: Washington, DC, 1984.


186

PESTICIDE SYNTHESIS THROUGH RATIONAL APPROACHES

physico-chemical properties will be discussed here l a r g e l y on this basis. For such o p t i m i s a t i o n i t i s necessary to understand the physico-chemical processes which contribute to t o x i c i t y or to e s t a b l i s h e m p i r i c a l r e l a t i o n s h i p s between physico-chemical p r o p e r t i e s and observed e f f e c t . The former approach c l e a r l y provides a more secure framework f o r p r e d i c t i o n and s e l e c t i o n of candidate components. The toxic e f f e c t produced by a chemical agent on a s u s c e p t i b l e organism depends on the nature and magnitude of i t s i n t e r a c t i o n s with the v i t a l processes which i t d i s r u p t s (which may be termed i t s intrinsic t o x i c i t y ) and on the amounts which reach the s i t e s of i n t e r a c t i o n . Both these determinants of t o x i c e f f e c t are expressions of b i o p h y s i c a l and physico-chemical f a c t o r s . The e f f e c t i v e n e s s of the l e t h a l interaction which i s equivalent to the i n t r i n s i c toxicity depends on the a f f i n i t y of the t o x i c a n t f o r the molecular c o n f i g u r a t i o n of the target s i t e and p o s s i b l y on i t s s t a b i l i t y to enzymatically regulated reactions. This i s reflected for example, i n the r e l a t i o n s h i p s between s t e r i c parameters and a c t i v i t y of a wide range of p e s t i c i d e s (1) or between chemical r e a c t i v i t y and a n t i c h o l i n e s t e r a s e a c t i v i t y of organophosphorus i n s e c t i c i d e s ( 2 ) . Quantitative treatment of the second determinant of toxic effect, dosage t r a n s f e r , i s o f t e n based on the p r i n c i p l e that r e l a t i v e i n j u r y i s some f u n c t i o n of ( i n many cases proportional to) the product of concentration (C) and time ( t ) i n s i t u a t i o n s where a constant concentration can be maintained. More generally the Ct product should be replaced by the i n t e g r a l Cdt which Hartley ( 3 ) termed the a v a i l a n c e . In p r a c t i c e , °two components of the availance can be d i s t i n g u i s h e d : first the processes of p e n e t r a t i o n , transport and chemical modification occurring within the organism which govern the way i n which the dose received at the surface of the organism i s transported to the s i t e of action and secondly the t r a n s f e r processes which must take place between the point of a p p l i c a t i o n and the r e c e i v i n g organism under any p r a c t i c a l conditions of use and which determine the p a t t e r n of concentration i n space and time to which the organism i s exposed. In many l a b o r a t o r y studies and screening t e s t s f a c t o r s of the second type are completely excluded as the compounds are a p p l i e d d i r e c t to the organism, while f a c t o r s of the f i r s t type are unavoidably integrated with the i n t r i n s i c t o x i c i t y i n the o v e r a l l measure of response. However, i t should be noted that even under such c o n t r o l l e d conditions the r e l a t i v e activity of different compounds may vary according to the dynamics of the treatment ( f o r example optimum L C ^ Q f° indefinite exposure, optimum L(CT)5o> 50 standard exposure time or L D ^ Q f ° discrete dose). This i s not merely of academic interest: 0

0

r

L C

f

o

r

a


r

a


12.

GRAHAM BRYCE

Optimization of Pesticide Properties

187

i t i s d e s i r a b l e to understand the dosage t r a n s f e r processes within the organism, which underlie such differences, in order to p r e d i c t optimum p r o p e r t i e s and s t r u c t u r e s and i n t e r p r e t c o r r e l a t i o n s found e m p i r i c a l l y . There i s an even stronger case f o r g i v i n g more a t t e n t i o n to dosage t r a n s f e r from the point of a p p l i c a t i o n to the r e c e i v i n g organism. With most p r a c t i c a l p e s t i c i d e treatments, only a very small proportion ( u s u a l l y l e s s than 1%) of the a p p l i e d dose achieves i t s intended e f f e c t : the remainder i s d i s s i p a t e d i n e f f e c t u a l l y i n the environment. This s i t u a t i o n i s l i k e l y to be aggravated with the trend to p r o g r e s s i v e l y more potent compounds because the powerful weathering, i n a c t i vating and r e d i s t r i b u t i o n processes which attenuate the applied dose are likely to have proportionately greater e f f e c t s as r a t e s of a p p l i c a t i o n f a l l ( 4 ) . Given the p r a c t i c a l ities of pesticide application and the dispersed nature of most target organisms, h i g h l y e f f i c i e n t u t i l i s a t i o n cannot be expected, but i t should be p o s s i b l e to achieve s u b s t a n t i a l improvements by optimising the physico-chemical properties which determine response to the attenuating processes. The optimal properties are unlikely to correspond precisely with those f o r most e f f e c t i v e i n t e r n a l t r a n s f e r to the target s i t e and there i s good evidence that they are not r e l a t e d to molecular s t r u c t u r e i n the same way as i n t r i n s i c t o x i c i t y . For example Briggs ( 5 ) found that the e l e c t r o n i c and p a r t i t i o n p r o p e r t i e s of h e r b i c i d a l Ν,Ν-dimethyl N phenyl ureas i n f l u e n c e d their relative inhibitory activity in the Hill reaction i n the opposite d i r e c t i o n to t h e i r e f f e c t s on s o i l adsorption which determines availability for uptake by plant roots and m o b i l i t y . I t follows that compounds found to be most a c t i v e when a p p l i e d d i r e c t l y to the organism i n screening t e s t s may d i f f e r considerably from those which would perform best in practice because physico-chemical properties have not been sufficiently considered and are therefore suboptimal. The i m p l i c a t i o n i s that the most e f f e c t i v e p r a c t i c a l compounds could be missed. 1

To seek compounds with optimal characteristics for e x t e r n a l and i n t e r n a l t r a n s f e r on a r a t i o n a l basis r e q u i r e s an understanding of pesticide availance and how this is influenced by physico-chemical and biophysical properties; to predict the most e f f e c t i v e compounds then requires a knowledge of the r e l a t i o n s h i p between these p r o p e r t i e s and molecular s t r u c t u r e . This paper b r i e f l y reviews the considerable progress which has been made i n these d i r e c t i o n s and the prospects f o r future advance. Optimal p r o p e r t i e s f o r i n t e r n a l t r a n s f e r to the target s i t e . The intense i n t e r e s t i n the discovery of potent b i o l o g i c a l l y active compounds has prompted various attempts to relate toxicity to molecular s t r u c t u r e and to c o d i f y the e f f e c t s


188


of s u b s t i t u e n t s on the t o x i c i t y of a parent s t r u c t u r e . E f f e c t s related to the chemical reactivity of the compound have been s u c c e s s f u l l y described i n terms of the f a m i l i a r free energy parameters Cf and rf * f o r e l e c t r o n i c or p o l a r i n f l u e n c e s and E f o r s t e r i c i n f l u e n c e s introduced by Hammett (6) and Taft (7). A more s o p h i s t i c a t e d modern treatment of steric i n f l u e n c e s i s the 'STERIMOL approach of Verloop (1). However we are here more concerned with penetration i n t o the organism and t r a n s l o c a t i o n to the s i t e of a c t i o n . Probably the most productive approach to systematising the p r o p e r t i e s i n f l u e n c i n g these processes i s that formulated by Hansch (8) which has subsequently generated much research i n t h i s f i e l d and was the subject of a multi-author review (9). The Hansch approach i s based on a physical model which envisages the toxicant reaching the target s i t e by a random walk through the various internal tissues and phases interposed between this site and the points of p e n e t r a t i o n . During t h i s passage the t o x i c a n t molecule i s presumed to be subject to numerous p a r t i t i o n s between phases of d i f f e r e n t p o l a r i t y . I t would be expected therefore that e f f e c t i v e n e s s of t r a n s f e r would be i n f l u e n c e d by the p a r t i t i o n i n g · properties of the molecule concerned and there i s a widely held view that there i s an optimum e f f i c i e n c y of t r a n s f e r at a f i n i t e value of the partition coefficient. s


1

The i n f l u e n c e of p a r t i t i o n and the e f f e c t s of s u b s t i t u e n t s are t r e a t e d q u a n t i t a t i v e l y by means of the substituent constant 7^ defined as l o g - log P where P i ? the p a r t i t i o n c o e f f i c i e n t i n favour of octanol from water of d e r i v a t i v e X and P is the partition coefficient of the parent molecule. This constant l i k e (f and E i s , to a f i r s t approximation, an a d d i t i v e property of the molecular groups comprising the molecule as discussed more f u l l y below. A major achievement of s t r u c t u r e - a c t i v i t y s t u d i e s i n recent years has been the demonstration that the r e s u l t s of many simple t o x i c i t y t e s t s can be c o r r e l a t e d to s t r u c t u r e by equations i n v o l v i n g various combinations of these constants (10, 11). I t has been considered that c o r r e l a t i o n s over a wide range of p a r t i t i o n c o e f f i c i e n t s r e q u i r e the i n c l u s i o n of a 7C term, the g e n e r a l i s e d c o r r e l a t i o n equation having the form:H

x

H

g

2

log (1/C)

2

= Κ'Λ - KTv + Κ 0.01

action

10

J

Table I I . P r o p e r t i e s of some r e p r e s e n t a t i v e s o i l - a p p l i e d pesticides Compound

Type

Ethylene dibromide

fumigant

0.02

0. 5

Dichloropropene

fumigant

0.05

2. 8

EPTC

residual herbicide

5.3

x 10

atrazine

residual herbicide

3.1

χ 1θ"

7

2. 9

dimethoate

soil insecticide

4.0

χ 10~

9

0. 3

disulfoton

soil insecticide

1.8

χ 10

lindane

soil insecticide

5

x 1θ"

5

25

ethirimol

f u n g i c i d e : seed treatment

1.1

χ 1θ"

7

33

paraquat

non-residual herbicide

ai

ρ

z water

-4

6. 0

-4

neg.

20

>10


5


12.

GRAHAM-BRYCE


197

Uptake by p l a n t s , i n s e c t s and f u n g i . Penetration i n t o plants f o r systemic a c t i o n and through the outer membranes of i n s e c t s and f u n g i i s a complex process which may involve compounds p e c i f i c metabolic or a c t i v e processes. Rigorous r e l a t i o n s h i p s with physico-chemical p r o p e r t i e s cannot therefore be expected. Nevertheless some broad general guidelines can be deduced. Uptake from soil by the underground parts of plants involves a s e r i e s of steps. Firstly the compound must be r e a d i l y a v a i l a b l e from s o i l which implies moderate adsorption as discussed above. The chemical must then be capable of entering the f r e e space, passing through the l i p o p h i l i c b a r r i e r s in the endodermis and have s u f f i c i e n t water s o l u b i l i t y to move i n s i g n i f i c a n t q u a n t i t i e s through the apoplast without being sequestered i n t o l i p o i d a l m a t e r i a l s which i t encounters in i t s path. Hence some compromise between h y d r o p h i l i c and lipophilic character is essential for optimum uptake and mobility with a tendency for hydrophilic properties to be more important. Thus compounds such as dimethoate (P = 6.3) are readily translocated whereas lindane 10 ) shows s l i g h t systemic p r o p e r t i e s ; a value of Ρ = 10 can be regarded as the l i m i t f o r a p o p l a s t i c systemic a c t i o n . Uptake and t r a n s location i n the symplast almost c e r t a i n l y i n v o l v e compounds p e c i f i c processes so that no general r e l a t i o n s h i p with p o l a r i t y can be deduced although i t i s c l e a r that the plasmalemma separating the apoplastic and symplastic systems i s much more permeable to l i p o p h i l i c than to h y d r o p h i l i c molecules. There i s , however, one means of achieving the c o n f l i c t i n g properties required for apoplastic transport without resort to compromise. This i s by using precursors which have c h a r a c t e r istics favouring uptake and are then converted w i t h i n the plant to a c t i v e t o x i c a n t s which are more r e a d i l y t r a n s l o c a t e d . The p r i n c i p l e i s best illustrated by the long-established organophosphorus i n s e c t i c i d e s of the systox type such as demeton, d i s u l f o t o n and phorate which are r e l a t i v e l y l i p o p h i l i c (log P-5) favouring uptake by the p l a n t . Once absorbed however they are o x i d i s e d at t h i o e t h e r and Ρ = S groups to give more polar products ( l o g P-'2.5) which, as i n d i c a t e d above, have polarity more appropriate f o r t r a n s l o c a t i o n ; they are also more e f f e c t i v e t o x i c a n t s and i n c i d e n t a l l y , more r e a d i l y degraded. Many other chemical conversions to give e i t h e r more polar or more l i p o p h i l i c products can be suggested, and i t should a l s o be recognised that the p r i n c i p l e can be elaborated advantage ously by e x p l o i t i n g c h a r a c t e r i s t i c s of dosage t r a n s f e r . For example experimental measurements and computation of uptake of organophosphorus i n s e c t i c i d e s from s o i l (17) suggest that for some compounds mass flow i n response to t r a n s p i r a t i o n may b r i n g l a r g e r q u a n t i t i e s of t o x i c a n t to the root surface than can be taken up, r e s u l t i n g i n an accummulation at the root s u r f a c e . I t i s a l s o know that there i s a gradient of pH across the rhizosphere and that the pH at the root surface



198


may o f t e n d i f f e r from the pH a few mm away by 1-2 u n i t s ( 1 8 ) . I t should t h e r e f o r e be p o s s i b l e to devise pH-sensitive precursors which would be converted effectively only i n the required r e g i o n f o r uptake to compounds of appropriate polarity: this would be e s p e c i a l l y b e n e f i c i a l where the products were l a b i l e and r e q u i r e d p r o t e c t i o n against degradation. Penetration into insects i s greatly influenced by the manner i n which the compound i s presented. C l a s s i c s t u d i e s by Treherne ( 1 9 ) i n d i c a t e d that when the t o x i c a n t i s supplied to detached insect cuticle i n aqueous solution penetration decreased with i n c r e a s i n g p o l a r i t y , e x p l i c a b l e on the assumption that p a r t i t i o n i n t o and passage through the l i p o i d a l e p i c u t i c l e is the rate determining step. In contrast several studies (20 22) have shown that when the toxicant i s dissolved in a suitable organic solvent penetration decreases with increasing oil/water p a r t i t i o n c o e f f i c i e n t . This i s consistent with the hypothesis that the organic solvents introduce the toxicant directly into the hydrophobic e p i c u t i c u l a r wax so that penetration i s determined by the r a t e at which the chemical moves from the wax through the u n d e r l y i n g more polar l a y e r s of the cuticle: t h i s would obviously be favoured by polar c h a r a c t e r . F i n a l l y i t should not be f o r g o t t e n that i n s e c t i c i d e s may be r e c e i v e d by i n s e c t s i n the absence of c a r r i e r s o l v e n t s , e i t h e r as vapour or i n c e r t a i n ULV a p p l i c a t i o n s . The vapour route i n p a r t i c u l a r may be of considerable importance for uptake both from s o i l and from l e a f surfaces as discussed further below. Under these c o n d i t i o n s uptake appears to be proportional to partition coefficient (23,24) which would be expected as the compounds must f i r s t pass unaided through the l i p o p h i l i c e p i c u t i c u l a r l a y e r . Penetration i n t o and accumulation by f u n g i are considered to be key f a c t o r s i n the s e l e c t i v e t o x i c i t y of many f u n g i c i d e s and again polarity appears to be a determining property. Indeed selectivity between f u n g i t o x i c i t y and phytotoxicity may w e l l be achieved by a t t a i n i n g the appropriate polarity in the f u n g i c i d e molecule so that i t can readily penetrate the fungus but not the plant cuticle. Rough c a l c u l a t i o n s from some of the published results for alkyl imidazolines and ethylenethioureas (25,26) suggest that the optimum for uptake by fungal c e l l s may be i n the r e g i o n of l o g P = 5 . 5 as compared with l o g P=4.5 f o r uptake of the same compounds by plant s u r f a c e s . More recent s t u d i e s by Brown and Woodcock with formamide fungicides (27) have also established the importance of p o l a r i t y i n a Hansch a n a l y s i s . Caution should be exercised i n seeking generalised conclusions because of d i f f e r e n c e s between fungal species i n c e l l w a l l c h a r a c t e r i s t i c s . Residual a c t i o n on plant s u r f a c e s . Many crop p r o t e c t i o n agents exert t h e i r e f f e c t s by r e s i d u a l a c t i o n f o l l o w i n g a p p l i c a t i o n to plant surfaces. In addition to photochemical stability,



12.

GRAHAM-BRYCE


199

the p r o p e r t i e s r e q u i r e d f o r such a p p l i c a t i o n s include reasonable a f f i n i t y f o r the plant surface to give r a i n f a s t n e s s , although not to the extent that the chemical i s rendered unavailable to damaging organisms i f the t o x i c a n t acts by contact e f f e c t s . For c o n t r o l of organisms on the plant surface sufficient v o l a t i l i t y to ensure vapour t r a n s f e r i s a l s o d e s i r a b l e , p a r t i c u l a r l y as most spray or granule a p p l i c a t i o n s leave a deposit i n the form of d i s c r e t e spots and a l a r g e proportion of the surface is effectively untreated. Approximate values may be assigned to the key p r o p e r t i e s i n the l i g h t of experience with representative p e s t i c i d e s . Rainfastness requires that the compound does not p a r t i t i o n r e a d i l y i n t o water from the material of the cuticular waxes: the example provided by some of the best known and most e f f e c t i v e contact i n s e c t i c i d e s such as DDT and the s y n t h e t i c pyrethroids suggests Log Ρ values of 6 to 7 are optimal: t h i s may be compared with the value of < 4 f o r t r a n s l o c a t e d compounds discussed above. The optimal vapour pressure will be such as to allow some vapour t r a n s f e r , but not give r i s e to r a p i d l o s s to the atmosphere by evaporation. This implies surprisingly low vapour pressures. The evaporative p o t e n t i a l of the atmosphere is s u b s t a n t i a l and could e a s i l y d i s s i p a t e 2 kg/ha/month of a p e s t i c i d e with a vapour pressure of 10 mm Hg ( 2 8 ) . The positive effects of vapour t r a n s f e r can be exemplified by calculating the quantity of t o x i c a n t (M) taken up i n time t by an i d e a l i s e d model i n s e c t , assumed to be a sphere of r a d i u s a. For p r a c t i c a l purposes t h i s i s given by:M =

4 ^ a

DtC

where D i s the vapour d i f f u s i o n c o e f f i c i e n t and C i s the uniform vapour concentration to which the i n s e c t i s exposed, which would approximate to the saturated vapour concentration (SVC) close to a p e s t i c i d e source. For i l l u s t y g t i o n _ ^ w e may consider phorate which has a SVC of about 1 . 2 χ 10 g ml at temperatures t y p i c a l l y o c c u r r i n g i n the f i e l d and f o r which D i s approximately 0.1 cm s . For a model aphid, a can be taken as 0 . 5 n g i , g i v i n g a p o t e n t i a l uptake over one hour of roughly 3 x 10 g which i s of the same order as the observed LD , consistent with experimental evidence f o r vapour e f f e c t s with x h i s compound. In the case of f u n g i c i d e s , Bent (29) found_^^clear evidence f o r vapour a c t i o n with drazoxolon (v.p. 4 χ 10 mm Hg) and oxythioquinox( ν .p. 2 χ 10 mm Hg) . Taken with other evidence, suc^i results suggest that vapour pressures i n the range 10 10 are appropriate: i t should be r e c a l l e d that the v o l a t i l i t y of the a c t i v e i n g r e d i e n t may be modified by formulation or by s o r p t i o n i n t o r e c e i v i n g s u r f a c e s . The various properties favouring particular types of a c t i o n are summarised i n Table I I I . I t must be s t r e s s e d that these can be c h a r a c t e r i s e d only i n very broad terms and that the type of a c t i v i t y may be shown to some degree by compounds f a l l i n g outside the s p e c i f i e d range, i n some cases as a r e s u l t



200

of i n d i v i d u a l f a c t o r s such as metabolic or chemical conversion. Nevertheless pesticides having the properties listed can be expected to give the corresponding patterns of behaviour; a b l e IV presents values f o r some r e p r e s e n t a t i v e translocated and contact pesticides for comparison, to complement those shown i n Table I I .

T

P r e d i c t i o n of s t r u c t u r e s


The are

having optimal

properties

various broad g u i d e l i n e s i n d i c a t e d i n the preceding i l l u s t r a t i v e only ana would have to be r e f i n e d by

Table I I I . Physico-chemical p r o p e r t i e s favouring of p e s t i c i d e a c t i o n Activity

Properties

Effective apoplastic translocation in plants

l o g Ρ 5

S e l e c t i v e uptake by fungal c e l l s

? l o g P/N.5.5.

sections detailed

d i f f e r e n t types

required

; v.p. < 1 0

mm

_^ -

10

mm

Hg


Hg

12.

GRAHAM BRYCE

201



Table IV. P r o p e r t i e s of r e p r e s e n t a t i v e t r a n s l o c a t e d and contact pesticides Vapour pressure (mm Hg at 20°C)

Type of a c t i o n

Compound

log^

dimethoate

0.8

4.1

χ 10"

ethirimol

1.3

9.4

χ 10

aldicarb

1.57

5.3

χ 1θ"

5

systemic nematicide and i n s e c t i c i d e

ioxynil

1.65

6.2

χ 10"

7

contact h e r b i c i d e with systemic a c t i v i t y

carbaryl

2.32

2.1

captan

2.54

linuron

C

-7

insecticide

systemic f u n g i c i d e

-5

contact i n s e c t i c i d e ; s l i g h t systemic properties

χ 10

;

5.0

χ 10"

6

2.76

8.6

χ 10"

6

lindane

3.2

9.4

χ 10"

6

parathion

3.93

3.8

DDT

6.0

1.9

χ 10"

7

permethrin

6.6

1.5

χ 10"

7

-5

χ 10

systemic

5

general f u n g i c i d e translocated herbicide

soil-applied

s o i l - a p p l i e d and contact i n s e c t i c i d e with some fumigant a c t i o n ; minimal systemic action non-systemic contact i n s e c t i c i d e with detectable vapour action non-systemic, p e r s i s t e n t contact i n s e c t i c i d e non-systemic, r e s i d u a l contact i n s e c t i c i d e .

(data from Hartley and Graham-Bryce ( 1 3 ) and Briggs ( 3 3 ) )




202

c o n s i d e r a t i o n of the dosage t r a n s f e r o b j e c t i v e s f o r the p a r t i c u l a r s i t u a t i o n envisaged i n order to a r r i v e at a d e t a i l e d specification for appropriate molecular properties. They demonstrate, however, that such s p e c i f i c a t i o n s can now be produced and that t h i s can and should be as much a part of d i r e c t e d r a t i o n a l synthesis as the consideration of toxicol o g i c a l properties. Having s p e c i f i e d the required properties, consideration must then be given to devising molecular structures which w i l l provide them. In t h i s connection a most valuable physicochemical p r i n c i p l e i s that the free energy increase, ÛG, i n the t r a n s f e r of a molecule between two phases i s an approximately a d d i t i v e property of the component groups. The p a r t i t i o n coefficient i s given by the exponent of Δ G/RT according to Boltzmann's law so that the l o g of the p a r t i t i o n c o e f f i c i e n t should also be an additive property. This p r i n c i p l e found earliest expression i n Traube's rule for surface tension. Where a molecule contains polar groups some modification of the simple a d d i t i v e r e l a t i o n s h i p may be necessary to allow for their interactions. Provided, therefore, the additive contributions for d i f f e r e n t s t r u c t u r a l components can be q u a n t i f i e d , the p a r t i t i o n coefficient can be r e a d i l y computed. A long e s t a b l i s h e d and convenient means f o r such q u a n t i f i c a t i o n i s already a v a i l a b l e i n the form of the parachor, which i s equivalent to the molar volume of a substance when i t s surface tension i s unity. Parachor i s primarily an additive property and there are extensive tabulations of parachor equivalents for various structural elements, such as that by Quayle (30). Parachor (H) can be r e l a t e d to p a r t i t i o n coefficient (P) using the r e l a t i o n s h i p of McGowan ( 3 1 ) : l o g Ρ = 0.012H + Ε a where Ε i s a term to allow f o r i n t e r a c t i o n s between hydrogenbonding groups where these are present. The parachor concept was f i r s t r e l a t e d to p e s t i c i d e behaviour i n s o i l by Lambert ( 3 2 ) and subsequently f u r t h e r developed by Briggs ( 3 3 ) . Briggs f u r t h e r showed that the a b i l i t y to c a l c u l a t e p a r t i t i o n c o e f f i cients as an additive property was particularly powerful when coupled with another physico-chemical p r i n c i p l e ennunciated by Collander (34) which shows that any p a i r of partition coefficients, P and Ρ , can be r e l a t e d by the expression:log ? = A l o g ? + B. The reason why t h i s combination of p r i n c i p l e s i s so powerful is that Briggs was a l s o able to demonstrate that the key properties discussed in earlier sections which determine p e s t i c i d e behaviour can be regarded as p a r t i t i o n s . Thus s o l u b i l i t y may be envisaged as a p a r t i t i o n between the compound i t s e l f and water, s o i l adsorption can be treated as a partition 1

2

1


12.


GRAHAM-BRYCE

203

between s o i l organic matter and water and so on. Hence i f the partition coefficient f o r one system can be c a l c u l a t e d using a d d i t i v e values, i t should then be p o s s i b l e to compute the other p r o p e r t i e s from the Collander r e l a t i o n s h i p . O c t a n o l / water p a r t i t i o n (P) i s an obvious reference system i n view of i t s widespread use i n s t r u c t u r e / a c t i v i t y s t u d i e s and knowledge of the parachor r e l a t i o n s h i p i n d i c a t e d above. The appropriate equations relating this reference system to key properties found by Briggs were:


Water s o l u b i l i t y

(WS)

For organic

liquids:-

log WS = 1 - l o g Ρ For solids i t i s necessary to introduce a f u r t h e r term to allow f o r the energy needed to break up the c r y s t a l s t r u c t u r e . The necessary c o r r e c t i o n long established by thermodynamic theory i s L T / R i T ^ T ) where Δ Τ i s the temperature d i f f e r e n c e between the melting point Τ and the temperature of measurement and L i s the l a t e n t heat of f u s i o n . For most compounds L increases with melting point and Briggs found the f o l l o w i n g expression a s a t i s f a c t o r y approximation: = -0.38

l o g WS

- l o g Ρ - (0.01

Τ

-

0.25).

m Soil

adsorption log P ° = 0 . 5 2 l o g Ρ + 0.41 0M where P^ i s the p a r t i t i o n c o e f f i c i e n t between s o i l organic matter (which i s the s o i l component having the dominant i n f l u e n c e on adsorption of most non-ionic p e s t i c i d e s ) and water. Vapour pressure. Vapour pressure (vp) of non-associated liquids can be r e l a t e d to temperature (T) using the i m p i r i c a l equation of McGowan ( 3 5 ) which i s based on a combination of Trouton's r u l e and the Clapeyron-Clausius equation as f o l l o w s : log vp = 5 . 6 - 2 . 7 (T / T ) ' b where T i s the b o i l i n g p o i n t . Vapour pressure at any temperature can thus be derived from a measurement of boiling point. Where the boiling point i s not readily available, or f o r consideration of h y p o t h e t i c a l s t r u c t u r e s , approximate boiling points can be c a l c u l a t e d by adding increments f o r s u b s t i t u e n t s to parent s t r u c t u r e s of known b o i l i n g point as shown by Briggs M

T W

T

1

7

fe

(36).

For solids, the crystal g i v i n g the e x p r e s s i o n : - 2.7

must

again

be

included

(T / T ) ' - (0.01 Τ - 0.25). b m Comparison of measured and p r e d i c t e d values log

vp = 5 . 6

factor 1

7

The concepts of defining the physico-chemical properties r e q u i r e d f o r various p e s t i c i d e treatments and then p r e d i c t i n g s t r u c t u r e s which w i l l have the intended characteristics may be i l l u s t r a t e d by r e f e r e n c e to dosage t r a n s f e r i n s o i l which



204


is often particularly demanding. T h i s will be exemplified by reference t o d i f f u s i o n of three compounds of c o n t r a s t i n g p r o p e r t i e s l i s t e d i n Table I I : the fumigant ethylene dibromide and the systemic organophosphorus insecticides disulfoton and dimethoate (28). It has already been pointed out that fumigant action r e q u i r e s favourable air/water p a r t i t i o n and weak adsorption: ethylene dibromide owes i t s success t o these p r o p e r t i e s which allow i t to move r a p i d l y i n s o i l a i r space. L i m i t e d adsorption i s a l s o e s s e n t i a l f o r a v a i l a b i l i t y t o plant r o o t s . The very weak adsorption of dimethoate thus makes i t r e a d i l y taken up from s o i l by p l a n t s , although i t i s a l s o vulnerable to downwash. The air/water partition properties of dimethoate r u l e out any p o s s i b i l i t y of vapour a c t i o n and a l s o make the compound very sensitive to s o i l moisture content, becoming virtually immobile i n dry s o i l s . The advantages of a vapour component are demonstrated by d i s u l f o t o n where the air/water p a r t i t i o n ensures a balancing of a i r and water pathways so that movement and a v a i l a b i l i t y are more or l e s s independent of moisture content. The stronger adsorption also protects against l e a c h i n g and r e t a i n s the chemical i n the intended zone without rendering the chemical u n a v a i l a b l e . The physicochemical p r o p e r t i e s of d i s u l f o t o n may be regarded therefore as approaching the optimal s p e c i f i c a t i o n f o r a s o i l applied systemic compound. To a s c e r t a i n how f a r i t might have been p o s s i b l e to anticipate the p r o p e r t i e s of these compounds i n advance, and p r e d i c t those f o r h y p o t h e t i c a l s t r u c t u r e s , measured values are compared i n Table I I I with values c a l c u l a t e d from the r e l a t i o n s h i p s given above. Vapour pressures f o r the organophosphorus compounds were estimated by applying b o i l i n g point increments f o r s u b s t i tuent groups t o the known value f o r (EtO)^ PSSEt. The agreement may be regarded as s a t i s f a c t o r y , except f o r the c a l c u l a t e d vapour pressure of dimethoate. T h i s may be due to i n a p p r o p r i a t e allowance f o r the melting point e f f e c t or i t may be that the measured value i s approximate bearing i n mind the d i f f i c u l t i e s of measuring low vapour pressures. Even allowing f o r t h i s discrepancy however the c a l c u l a t i o n s are adequate t o c l a s s i f y the d i f f e r e n t compounds and p r e d i c t broad patterns of behaviour. Clearly much more elaborate treatments are p o s s i b l e , particularly i f s i m u l a t i o n modelling i s employed, but such results give encouragement f o r f u r t h e r development of t h i s approach and f o r g i v i n g more a t t e n t i o n to these physicochemical f a c t o r s which have such a profound i n f l u e n c e on e f f i c a c y and performance. I b e l i e v e that John S i d d a l l , whom t h i s symposium commemorates would have approved of t h i s view as r e p r e s e n t i n g a further component of the r a t i o n a l approach t o p e s t i c i d e design which h i s work so c l e a r l y represented.



a

p

1

o

u

1

r

d water Ρ .„ air

Κ

pressure mm Hg

V

m

Solubility S

41.1

ft

2.3

0.5

40

11.3 * ^ Λ

4700

calculated

11.0 '' ~

4300

measured

dibromide

Ethylene

0

4

-6

2.5x10

0.28

8.5x10

2.5xl0

measured

0

7 1.27xl0'

J

-5

0.34

J

4

8.2x10

1.3xl0

1

calculated

Dimethoate

Q

1

5500

0

-4

25.1

1.8x10 - ^

25

-4

65ΟΟ

37.3

3.4x10

32

calculated

Disulfoton

f o r representative

measured

Table V. Comparison of measured and c a l c u l a t e d p r o p e r t i e s soil-applied pesticides



206

Acknowledgments


I thank Dr. G.G. Briggs f o r h e l p f u l d i s c u s s i o n s about vapour pressure c a l c u l a t i o n s .

Literature Cited 1. Verloop, A, Phil. Trans. R. Soc. Lond. 1981, Β 295, 45-55 2. Fukuto, T.R. in "Insecticide Biochemistry and Physiology": Wilkinson, C.F., Ed; Plenum Press: New York, 1976; Chap.11. 3. Hartley, G.S., J . theor. Biol. 1963, 5, 57. 4. Graham-Bryce, I.J., Phil. Trans. R. Soc. Lond. 1981, Β 295, 5 5. Briggs, G.G., Rep. Rothamsted Exp. Stn for 1976 1977, 185. 6. Hammett, L . P . , "Physical Organic Chemistry", McGraw-Hill: New York, 1940. 7. Taft, R.W., in "Steric Effects in Organic Chemistry": Newman, M.S., Ed.: Wiley: New York, 556. 8. Hansch, C.; Fujita, T . , J . Am. Chem. Soc. 1964, 86, 1616. 9. ADVANCES IN CHEMISTRY SERIES No. 114, American Chemical Society: Washington, D.C., 1972 10. Hansch, C., in ADVANCES IN CHEMISTRY SERIES No. 114, American Chemical Society; Washington, D.C., 1972, p. 20. 11. Fujita, T . , in ADVANCES IN CHEMISTRY SERIES No. 114, American Chemical Society: Washington, D.C., 1972, p.1. 12. Briggs, G.G.; Elliott, M.; Farnham, A.W.; Janes, N.F.; Needham, P.H.; Pulman, D.A.; Young, S.R., Pestic. Sci. 1976, 7, 236. 13. Hartley, G.S.; Graham-Bryce, I . J . "Physical Principles of Pesticide Behaviour", Academic Press; London, 1980. 14. Penniston, J . T . ; Beckett, L . ; Bently, D.L.; Hansch, C., Mol. Pharmacol. 1969, 5, 333. 15. Dearden, J . C . ; Townend, M.A., in "Herbicides and Fungicides, Factors Affecting their Activity", McFarlane, N.R., Ed.; Special Publication No. 29, Chemical Society: London, 1977. 16. Soderlund, D.M., in "Insect Neurobiology and Pesticide Action (Neurotox)79 " Society of Chemical Industry: London, 1980 p. 449. 17. Graham-Bryce, I . J . in "Physico-chemical and Biophysical Factors Affecting the Activity of Pesticides", Monograph No. 29, Society of Chemical Industry: London, 1968, p. 251. 18. Nye, P.H., Plant and Soil 1981, 61, 7. 19. Treherne, J.E., J. Insect Physiol. 1957, 1, 178. 20. Olson, W.P.; O'Brien, R.D., J . Insect. Physiol. 1967, 9, 777. 21. Buerger, Α.Α.; O'Brien, R.D., J . Cell. Comp. Physiol. 1965, 66, 227. 22. Szeicz, F.M.; Plapp, F.W.; Vinson, S.B. J . econ. Ent. 1973, 66, 9. 23. Zschintzsh, J.; O'Brien, R.D.; Smith, E.H. J . econ. Ent. 1965, 58, 614. 24. Bracha, P.; O'Brien, R.D., J . econ. Ent. 1966, 59, 1255. 25. Wellman, R.H.; McCallam, S.E.A., Contr. Boyce Thompson Inst. 1946, 14, 151.



12.

GRAHAM-BRYCE


26. Ross, R.G.; Ludwig, R.A., Canad. J . Bot. 1957, 35, 65. 27. Brown, D.; Woodcock, D., Pestic Sci 1975, 6, 371. 28. Graham-Bryce, I . J . in "The Chemistry of Soil Processes", Greenland, D.J.; Hayes, M.H.B., Eds; John Wiley and Sons; London, 1981, Chap. 12. 29. Bent, K . J . , Ann. appl. Biol. 1967, 60, 251. 30. Quayle, O.R., Chem. Rev. 1953, 53, 439. 31. McGowan, J . C . , Nature (London) 1963, 200, 1317. 32. Lambert, S.M., J . Agric. Fd. Chem. 1967, 15, 572. 33. Briggs, G.G., J. Agric. Fd Chem. 1981, 29, 1050. 34. Collander, R., Acta Chem. Scand. 1951, 5, 774. 35. McGowan, J . C . , Rec. Trav. Chim. Pays-Bas et Belg. 1965, 84, 99. 36. Briggs, G.G., Proc. 1981 Brit. Crop Prot. Conf - Pests and Diseases, 1981, 3, 701. RECEIVED February 13, 1984


207

Optimization of Physicochemical and Biophysical Properties of

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