Computers C/tern. Vol. 16, No. 3, pp. 195-199, 1992 F’rinted in Great Britain. All rights reserved

GO97-i3485/92 $5.00 + 0.00 Copyright 0 1992 Pcrgamon Press Ltd

CORRELATION ANALYSIS IN STRUCTURE AND CHROMATOGRAPHIC DATA OF ORGANOPHOSPHORUS

COMPOUNDS BY GA1

Lu Xv,* HUA-YIJN WANG~ and QIANG Su Changchun Institute of Applied Chemistry, Academia Sinica, Changchun 130022, Jilin,

People’s Republic of China

(Received II April 1991; in revised form 23 March 1992)

Abstract-This approach is undertaken to examine the correlation ability of the general a,-index (GAI) to predict chromatographic behavior. The test is performed on various types of organophosphorus compounds. The results demonstrate that the GA1 possesses a good correlation with chromatographic properties.

INTRODUCTION

In the past, there have been two main types of methods for predicting new compounds. The first one is to determine the molecular structure: molecular properties can he derived in principle by applying quantum mechanics to the molecular structure. The results obtained can be applied only to the specific molecule considered, and they do not provide infor- mation that could be expected for related molecules. The second method is to determine the properties of basic fragments by analyzing a set of molecules. Then the molecular properties can be derived by combining these fragmental properties. In this way the chemist often encounters the following problems: (I) How can one extrapolate the behavior for new compounds from compounds already studied? (2) How can one deduce the behavior of a known compound from properties of already known compounds?

It is well known that the chemical behavior of a compound is dependent upon its structure. Balaban (1988) outlined the situation in an opinion, “one should bear in mind that whereas chemical structures are discrete entities whose quantitative aspects are not apparent, their properties show a continuous variation which is expressed within a certain numeri- cal range. Topological indices (Tls) bridge this gap by establishing a correspondence between structures and a non-dimensional numerical scale.”

More than 100 TIs have been proposed to date (Rouvray, 1984). This plethora of topological indices is reasonable because some Tls better express one property, while others better apply to another prop erty. Only a few of them however, have found wide

* Author for corresoondence. t Present address: Ihstitutc of Theoretical Chemistry, Jilin

University, Changchun 130021, People’s Republic of China.

application in chemistry for correlational studies involving the physicochemical and other molecular properties. Although the TIs are suitable for describ- ing a broad range of problems, there are some cases in which they do not yield good correlations. It is hoped that it will be possible to devise a specialized index for determining specific chemical properties.

A topological index, GAI, proposed by the authors (Xu et af., 1992) is defined as the absolute value of the constant of the characteristic polynomial derived from the matrix orbital interactions matrix of linked atoms (OIMLA). GA1 was found to be valuable in the discrimination of cis/trans isomerism, and yielded good correlations with several physicochemical prop- erties of hydrocarbons and of neutral organophos- phorous compounds.

In the present study we will test the applicability of the GA1 to correlations of molecular species such as organophosphoms compounds, with properties which have not previously been investigated by use of Tls.

The application of TIs to predict the chromato- graphic behavior of a variety of organic compounds has been discussed in several papers. Good corre- lations between the experimental retention indices obtained by gas chromatography and the Tls such as molecular connectivity indices (Kier & Hall, 1976, 1986; Randic, 1978; Doherty et al., 1984; Jinno & Kawasaki, 1983; Bojarski & Ekiert, 1982; Szasz el al., 1983) and Wiener numbers (Wiener, 1947; Bonchev et al., 1979) have been established. The Rf and the R, values for paper chromatography and thin-layer chromatography have also been used to yield such correlations (Bojarski & Ekiert, 1982; Szasz et al., 1983; Kaliszan & Foks, 1977). But the studies on the relationships between the topological indices and the mobility values for paper electrophoresis have not been reported. There are few studies on the corre- lation between the Tls and the physico-chemical

195

196 Lu xu et al.

Table 1. GA1 and RF values of four types of neutral organophosphorus compounds with different mobile phases

Compounds GA1 R,(l) R, (2) R, (3) Rr (4) Rr (5)

(C,H,G),PG 0.2991 0.29 0.12 0.10 0.72 0.54 C,H,WOC,H,)I 0.4253 0.36 0.17 0.15 0.63 0.43 (C,H,),PW&W 0.6016 0.45 0.27 0.24 0.41 0.39 (C,H,),W 0.8489 0.60 0.47 0.44 0.25 0.18

properties of organaphosphorus compounds in the literature. In the present work, we focused on deter- mining the use of GA1 for describing the behavior of paper chromatography, paper electrophoresis and gas chromatography of organophosphorous compounds.

RESULTS AND DISCUSSION

The method for computing GA1 has been discussed in detail in the references (Xu et al., 1992), hence it is not given here. The GA1 and the observed R, values (Xu & Yuan, 1987) of the four types of neutral organophosphorus compounds with different mobile phases examined in the present study are shown in Table 1. The mobile phases are as follows: (1) dioxane-water (I : 1, v/v), (2) methylalcohol-water (3: 7, v/v). (3) tetrahydrofuran-water (4,6, v/v), (4) hexane-methylbenzene (1: I, v/v), (5) hexane.

As can be seen from Table 1, GA1 increases rapidly with replacement of the alkoxy group (OC,H,) by the alkyl radical (C,H,) directly connected to the phosphorous atom. The Rr value increases for polar mobile phases, and decreases for nonpolar mobile phases. The major difference among the (C,H,)mPO(GC,H.&

compounds (nt = 0, 1,2,3, n = 3 - m) is the numbers of oxygen atoms connected to the phosphorus atoms. The fewer there are of such oxygen atoms, the larger the polarity of the compound becomes. The R, values are dependent on the polarities of the compounds for both polar and nonpolar mobile phases (as shown in Table 1). Thus we expect the molecular polarities of the compounds studied to be well described by the GAI.

The GA1 and the observed R, values (Xu & Yuan, 1987) of dialkyl methylphosphonates and dibutyl

Table 2. GA1 aad observed R, values of alkyl dialkylphosphonates RPO(OR’),

R R GA1 Rr (A)

Methyl Ethyl 0.6434 0.80 Methyl Propyl 0.5739 0.71 Methyl Butyl 0.51 IS 0.62 Ethyl BUIYl 0.4773 0.59 Propyl Butyl 0.4505 0.53 Methyl Pentyl 0.4558 0.48 Butyl Butyl 0.4253 0.46 Methyl Hcxyl 0.4062 0.38 Pentyl Butyl 0.4015 0.38 Hexyl Butyl 0.3790 0.34 Hcptyl Butyl 0.3578 0.26 Methyl Heptyl 0.3620 0.24 Gcty1 Butyl 0.3378 0.22 Methyl OCWI 0.3226 0.15

alkylphosphonates investigated in the present study are shown in Table 2.

For CHS PO(OR’)2 compounds, the GA1 decreases with increasing carbon number in the straight-chain R’ group. For RPO(OC,H,), compounds, GA1 decreases as we go from compounds with 4-8 carbon atoms in the straight-chain R’ group (Table 2). Figure 1 shows the plot of the observed RI values and the GAI. The straight line reveals that GA1 can be employed to describe paper chromatographic behavior of dialkylalkylphosphonates.

The GA1 and observed Rr values (Xu & Yuan, 1987) of the four types of neutral organophosphorus compounds are listed in Table 3. The chromatogram was developed in methyl-alcohol-water (4:6) as the mobile phase.

Figure 2 shows plots on a logarithmic scale of the GA1 vs logarithmic scale of the Rf values for the four types of neutral organophosphorus compounds, including trialkylphosphates, dialkyl alkylphos- phonates, alkyl dialkylphosphonate and trialkylphos- phine oxide. The least squares fit of this curve produced the following equation:

Ln(R& = 0.20Ln(GAI) - 0.30 (1)

n = 12, r = 0.96, s = 0.033

Equation (1) illustrates that the various substituted groups of molecules studied can be combined into a single regression model containing one variable. The calcdated Rf values of the 12 neutral organophos- phorus compounds are consistent with the observed values.

0.8

05

I I I I I

0.35 045 0.55 065

GA1

Fig. 1. Correlation between the GA1 and observed R, values of ICdialkyl alkylphosphonates.

Correlation analysis by GA1 197

Table 3. GA1 and the I?~ values of four types of neutral organophos- phorur compounds

Compound type R GA1 R, (Cornput.) Rr (Exp.)

Butyl 0.2997 0.58 0.61 (RG), PO Hcptyl 0. I785 0.53 0.53

Z-Ethylhexyl 0. I323 0.50 0.49

Butyl 0.4253 0.63 0.63 RPO(GR), Heptyl 0.2532 0.56 0.54

2-Ethylheyl 0.1876 0.53 0.51

Butyl 0.6016 0.67 0.65 RSWR) Hcptyl 0.3785 0.61 0.62

2-Ethylhtyl 0.2651 0.57 0.60

Butyl 0.8489 0.72 0.70 RlPG Heptyl 0.5051 0.65 0.66

2-Ethylhtxyl 0.3896 0.61 0.62

The correlation analyses presented above (Figs 1 and 2) obviously show that the changes of the GA1 reflect variations in the Rr values of the neutral organophosphorus compounds. The R, values are qualitatively predictable from the GA1 of the com- pounds, showing increases in the RI value with in- creasing GA1 for polar phases, but a decrease of the RI value with increasing GAI for nonpolar phases. It also shows that the one-variable model is sufficient to obtain good correlations.

The GA1 and observed RI values, mobility values (Long & Yuan, 1985) of monoalkyl and dialkyl phosphoric acids with 2-8 carbon atoms in the alkyl group by paper chromatography and paper electro- phoresis are presented in Table 4. The paper chroma- tography was developed in alcohol-25% ammonium hydroxide-water (6 : 3 : 1, v/v/v) as the mobile phase. Paper electrophoresis was performed in the buffer acetic acid-pyridine-water (5 : 5: 90, v/v/v, pH 4.4).

For the two types of R,PO(OH) and RPO(OH)2 compounds, GA1 decreases with an increase in the number of carbons in the alkyl group. When the carbon number of the R group < 5, the value of GA1 for R,PO(OH) is larger than that for RPO(OH), within the same alkyl group, while the GA1 for R,PO(OH) is smaller than that for RPO(OH), when the carbon number of the R group > 5; this indicates that the GA1 of RIPO(OH) decreases with an increase in the carbon number of the R group, by a greater factor than that of RPO(OH),. For

I I I I

0.5 09 1.3 1.7

-Ln (GA1 ) Fig. 2. Plots on a logarithmic scale of the GA1 against the RI values for four types of neutral organophosphorus

compounds; r = 0.98, s = 0.04, n = 14.

monoalkyl and dialkyl phosphoric acids, the R, values of the former are smaller than those of the latter with the same alkyl group and they increase with an increase in the number of carbon atoms in the alkyl group. Contrary to the behavior in paper chromatography, the mobility values of the former in paper electrophoresis are greater than those of the latter with the same alkyl group and they decreases as the number of carbon atoms in the alkyl group increase. Figure 3 shows the plot of the R, values vs the GA1 of monoalkyl and dialkyl phosphoric acids,

04 0.6 0.6 10

GA1 Fig. 3. Plot of the R, values vs the GA1 of acidic organo-

phosphorus compounds.

R

Ethyl

Table 4. GAI, the RI and mobility values of compounds R,PG(OH) and RPG(OH),

GA1 R, Mobility value (MV)

R, PWGH) RPWJH), Rs P’XGH) RPO(GH), R,PO(OH) RPO(OH), I.0001 0.8310 0.80 a.55 t-.9(1 n 94 Probyl 0.8910 0.7844 0.84 0.59 0.74 0.84 _._

Isa-propyl 0.8063 0.7464 0.84 0.59 0.70 0.79 Butyl 0.7940 0.7405 0.85 0.61 0.62 0.72 Pcntyl 0.7076 0.6990 0.87 0.64 0.53 0.63 Hcxyl 0.6306 0.6599 0.87 0.64 0.41 0.58 Hcptyl 0.5620 0.6230 0.88 0.67 0.09 0.54 axyl 0.5004 0.5881

0:s - 0.05 0.49

2-Ethylhcxyl 0.4598 0.5635 0.69 0.007 0.46 I-Methylheptyl 0.4526 0.5592 - - 0.01 0.44

198 Lu Xu et al.

07

0.5 06 0.7 08 09 1.0

GA1

Fig. 4. Plot of the GA1 and mobility values of monoalkyl and dialkyl phosphoric acids. Line A: r = -0.93, s = 0.011,

n=8;lineB:r=-D.98,s=O.O09,n=8.

The regression analyses of GA1 against the mobility values (MV) of monoalkyl (equation 2) and dialkyl (equation 3) phosphoric acids give:

MV = I .76 GA1 - 0.79 (2)

n = 11, r =0.98, s = 0.069

MV = 1.78 GAI - 0.57 (3)

n=ll, r = 0.99, s = 0.029

It is evident that both above equations give almost identical slopes. In Fig, 4 the experimental mobility

values are plotted against the GA1 for monoalkyl and dialkyl phosphoric acids, respectively. The two lines are parallel to each other. Hence the increase of the GA1 results in the increase of the mobility values for both kinds of alkylphosphoric acids. This reveals an important advantage of the GA1 approach for pre- dicting mobility values of acidic organophosphorus compounds.

The GA1 and observed retention index (I) and corrected retention time (tk) values of 30 acidic organophosphorus compounds for gas chromatog- raphy (Long & Yuan, 1985) are shown in Table 5. These molecules include four types of phosphonite: dialkylphosphonate, alkyl cyclohexylphosphonate, alkyl phenylphosphonate and dialkylphosphoric acid. We have found that it is difficult to describe all the acidic phosphorus-containing compounds by a single regression. The results of correlation analyses for each type am given in Table 6. The lowest correlation coefficient is 0.92.

CONCLUSION

The GA1 model has been shown to predict success- fully the chromatographic data for various phos- phorus-containing compounds. Our results also indicate that the GA1 index can be employed to relate the structural features to chromatographic behaviors of organophosphorus compounds. The following regularities were found: (1) replacement of the alkoxy group (OR) by alkyl radicals (R) bonded to the central atom P will raise the GAL With an increase

Table 5. GA1 and the t’. and I values of acidic oraanophosphotus compounds

Comaound tv~e R R GA1 r; I

RPO(OR’)OH

Butyl I-Methylpropyl Pentyl 3-Methylbutyl Hexyl Heptyl octy1 Z-Methylhexyl 1-Methylheptyl Nonyl DCCYI

-

-

- -

-

0.3954 58 1666 0.3771 30 1508 0.3524 124 1849 0.3246 77 1741 0.3141 259 2033 0.2797 54.5 2213 0.2494 I157 2398 0.2379 447 2165 0.2292 501 2192 0.2223 2477 2578 0.1981 5310 2761

Cyclohexyl Ethyl 0.4743 67 1704 Cyclohexyl ROPYl 0.4479 92 1789 cyclobexyl Pentyl 0.3992 202 1974 Cyclohexyl Hcxyl 0.3769 290 2060 Cyclohexyl Heptyl 0.3558 422 2151 Cyclohexyl octy1 0.3356 597 2235 Cyclohexyl I-Methylheptyl 0.3280 367 2117 Cyclohexyl 2.Methylhexyl 0.3219 392 2133 Phenyl Butyl 5.8238 162 1921 Pbenyl Hexyl 5.1902 347 2104 Phenyl oayl 4.6254 782 2302 Phenyl I-Methylhcptyl 4.5170 452 2168 Phenyl 2.Ethylhexyl 4.4338 507 2195 Phenyl D=Yl 4. I222 1697 2419 Phenyl Undecyl 3.8915 2507 2581

Butyl - 0.7940 57 1662 0.6306 260 2034 0.5620 547 2214 OSOiI4 1147 2396

R,PO(OH) H&y1 Heptyl OCtyi

Correlation analysis by GA1

Table 6. Rearession results obtained from Table 5

199

VW, WOW I1 -0.93 0.074 11 -0.92 0.658

RPO(OR’)OH 8 -0.96 0.238 8 -0.96 0.029 (R=C&,-) RPO(OR’)OH 7 -0.92 0.405 7 -0.93 0.041 (R = CLHJ_)

R,PO(OH) 4 - I .oo 0.094 4 -1.00 22.1

in the GAI, the RI value will increase for polar phases, and decrease for nonpolar phases. (2) The GA1 decreases with an increase in the chain length, and/or an increase in branching, i.e. the molecular compact- ness. With a decrease in the GAI, the Rf value decreases for polar phases for neutral organo- phosphorus compounds, but increases for acidic organophosphorus compounds, and the mobility value decreases for all the compounds discussed. The quality of the correlations of chromatographic behaviors with the GA1 reveals that the GA1 contains important structural information, and provides a potential technique for the prediction the properties of unknown compounds.

A complete program is available for a nominal fee, on request.

Rcknowledgemenrs-Financial support for this work from the Center for Scientific Database, Academia Sinica, is gratefully acknowledged.

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