QSAR Models for Insecticidal Properties of Plant Essential Oils on the Housefly (Musca domestica L.)

Pablo R. Duchowicza,*, Daniel O. Bennardib, Erlinda V. Ortizc, and Nieves C. Comellid,e 
	
a Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (INIFTA), CONICET, UNLP, Diag. 113 y 64, C.C. 16, Sucursal 4, 1900 La Plata, Argentina
b Cátedra de Química Orgánica, Facultad de Ciencias Agrarias y Forestales, UNLP, 60 y 119, 1900 La Plata, Argentina 
c Instituto de Monitoreo y Control de la Degradación Geoambiental (IMCoDeG), CONICET, Facultad de Tecnología y Ciencias Aplicadas, Universidad Nacional de Catamarca, Maximio Victoria 55, 4700 Catamarca, Argentina
d Centro de Investigaciones y Transferencia de Catamarca (CITCA), CONICET, Universidad Nacional de Catamarca, Prado 366, 4700 Catamarca, Argentina
e Facultad de Ciencias Agrarias, Universidad Nacional de Catamarca, 4700 Catamarca, Argentina

*Corresponding author. Telephone: (+54)(221)4257430, Fax: (+54)(221)4254642, E-mail: pabloducho@gmail.com

Table 1S. Mass fraction composition (w) of components of the 27 studied plant essential oils.
EOID a	ID b	Chemical name	w	
1 [33]	1	Bornylacetate	0.342	
	2	Camphene	0.175	
	3	α-Terpinene	0.067	
	4	α-Pinene	0.059	
	5	Limonene	0.055	
	6	Borneol	0.029	
	7	α-Bisabolene	0.023	
	8	trans-Caryophyllene	0.019	
	9	Tricyclene	0.013	
	10	Santene	0.013	
	11	α-Caryophyllene	0.012	
2 [34]	12	(Z)-Asarone	0.853	
	13	(E)-Asarone	0.027	
	14	γ-Asarone	0.021	
	15	Linalool	0.017	
	16	(Z)-Methyl isoeugenol	0.017	
3 [35]	17	5,7-Dimethoxycoumarin	0.158	
	18	3-Methyl-1,2-cyclopentanedione	0.083	
	19	1-Methoxycyclohexene	0.080	
	20	Corylone	0.069	
	21	Palmitic acid	0.069	
	22	5,8-Dimethoxypsoralen	0.061	
	23	α-Terpineol	0.060	
	24	Umbelliferone	0.044	
	25	Resorcinol	0.037	
	26	Caryophyllene oxide	0.030	
	27	7-Methyl-(Z)-8-tetradecen-1-ol acetate	0.028	
	28	Citral	0.022	
	29	Spathulenol	0.020	
	30	Geranyl acetone	0.018	
	31	2,3-Dimethyl-2,3-butanediol	0.017	
	32	Terpinen-4-ol	0.017	
	33	Linalool oxide	0.012	
	34	Geraniol	0.012	
	35	(Z)-8-Methyl-9-tetradecenoic acid	0.012	
	36	3,7-Dimethyl-(Z)-2,6-octadienal	0.011	
	37	5-Methoxypsoralen	0.011	
4 [36]	38	limonene	0.546	
	39	γ-terpinene	0.191	
	40	β-pinene	0.145	
	41	α-pinene	0.039	
	42	geranial	0.023	
	43	myrcene	0.015	
	44	neral	0.011	
5 [37]	45	eugenol	0.772	
	46	eugenyl acetate	0.150	
	47	β-caryophyllene	0.057	
6 [38]	48	Cedrol	0.388	
	49	Thujopsene	0.301	
	50	Widdrol	0.056	
	51	α-cedrene	0.040	
	52	β-cedrene	0.020	
7 [39]	53	Linalool	0.415	
	54	1,8-Cineole	0.141	
	55	Borneol	0.098	
	56	Camphor	0.078	
	57	Linalyl acetate	0.040	
	58	Citronellal	0.021	
	59	cis-Linalool oxide	0.014	
	60	Caryophyllene oxide	0.014	
	61	Octan-3-one	0.013	
	62	Hexyl butyrate	0.011	
8 [40]	63	geranial	0.477	
	64	neral	0.411	
	65	Citronellal	0.035	
	66	β-caryophyllene	0.027	
	67	linalool	0.011	
9 [41]	68	1,8-cineole	0.502	
	69	α-pinene	0.101	
	70	(E)-nerolidol	0.078	
	71	limonene	0.075	
	72	α-terpineol	0.061	
	73	viridiflorol	0.060	
	74	β-pinene	0.027	
	75	γ-terpinene	0.017	
	76	β-caryophyllene	0.015	
10 [42]	77	Menthol	0.714	
	78	p-Menthone	0.080	
	79	Iso-Menthone	0.054	
	80	Neo-Menthol	0.032	
	81	Pulegone	0.022	
	82	Isopulegone	0.020	
	83	1,2-Benzenedicarboxylic acid	0.016	
	84	1-α-Terpineol	0.015	
	85	3-Octanol	0.012	
11 [43]	86	linalyl acetate	0.518	
	87	Linalool	0.312	
	88	limonene	0.015	
	89	isopinocamphone	0.013	
12 [6]	90	Pulegone	0.833	
	91	Piperitenone	0.086	
13 [44]	92	Carvone	0.571	
	93	Dihydrocarveol	0.080	
	94	Menthol	0.054	
	95	Pulegone	0.038	
	96	Dihydrocarveol acetate	0.034	
	97	Menthone	0.032	
	98	Linalool	0.020	
	99	β-Cubebene	0.019	
	100	Dihydrocarvone	0.017	
	101	Caryophyllene	0.013	
	102	Isomenthone	0.011	
14 [45]	103	Linalool	0.460	
	104	Methyl chavicol	0.138	
	105	1,8 Cineol	0.071	
	106	Methyl eugenol	0.049	
	107	(E)-Methylcinnamate	0.044	
	108	α-Bisabolol	0.038	
	109	Eugenol	0.026	
	110	α-Bergamotene	0.026	
	111	Bornyl acetate	0.013	
	112	γ-cadinene	0.012	
15 [46]	113	Carvacrol	0.581	
	114	p-Cymene	0.114	
	115	Thymol	0.090	
	116	γ-Terpinene	0.071	
	117	Linalol	0.020	
	118	Myrtenal	0.019	
	119	β-Caryophellene	0.016	
	120	Myrcene	0.012	
	121	Octen-3-ol	0.011	
	122	α-Terpinene	0.011	
16 [47]	123	1,30-Dibromotriacontane	0.411	
	124	11-Tricosene	0.154	
	125	1,38-Dibromooctatriacontane	0.098	
	126	1-Pentacontanol	0.091	
	127	O-2-Methylpropyl-hydroxylamine	0.070	
	128	2-Piperidinone, N-[4-bromo-N-butyl]	0.064	
	129	2-Methyl-tricosane	0.031	
	130	9-Cyclohexyl-eicosane	0.022	
	131	1,54-Dibromo-tetrapentacontane	0.015	
	132	2,4,6-Tritert-butyl-4-methyl-2.5-cyclohexadien-1-one	0.014	
17 [48]	133	Carvacrol	0.597	
	134	Thymol	0.137	
	135	γ-Terpinene	0.110	
	136	p-Cymene	0.076	
	137	Myrcene	0.013	
	138	α-Terpinene	0.011	
18 [49]	139	Isomenthone	0.790	
	140	cis-β-ocimene	0.041	
	141	Myrcene	0.040	
	142	Menthone	0.017	
	143	Limonene	0.014	
	144	α-Phellandrene	0.011	
	145	Nerodinol	0.011	
19 [50]	146	Citronellol	0.225	
	147	Geraniol	0.182	
	148	Linalol	0.109	
	149	Citronellyl formate	0.086	
	150	Isomenthone	0.066	
	151	Geranyl formate	0.064	
	152	Terpinen-4-ol	0.060	
	153	Menthone	0.034	
	154	Geranial	0.014	
	155	Nerol	0.012	
20 [51]	156	Patchouli alcohol	0.258	
	157	δ-Guaiene	0.148	
	158	α-Guaiene	0.119	
	159	α-Patchoulene	0.113	
	160	Seychellene	0.084	
	161	Viridiflorol	0.058	
	162	β-Caryophyllene	0.050	
	163	β-Patchoulene	0.047	
	164	1-(Propen-2-yl)-4-methylspiro[4,5]decan-7-one (isomer B)	0.025	
	165	Valencene	0.020	
	166	Aromadendrene oxide	0.015	
	167	Selina-3,7(11)-diene	0.011	
	168	7-Oxabicyclo[4,1,0]heptane, 1,3,3-trimethyl-2-(3-methyl-1,3-butadienyl)-	0.011	
21 [46]	169	Borneol	0.156	
	170	α-pinene	0.153	
	171	1,8-Cineole	0.116	
	172	Camphre	0.116	
	173	Verbenone	0.112	
	174	Linalol	0.054	
	175	Limonene	0.038	
	176	Camphene	0.034	
	177	α-Phellandrene	0.021	
	178	p-Cymene	0.020	
	179	α-Terpineol	0.020	
	180	Bornyl acetate	0.014	
	181	Myrcene	0.013	
22 [52]	182	1,8-Cineole	0.453	
	183	Camphor	0.113	
	184	Camphene	0.059	
	185	α-pinene	0.051	
	186	β-pinene	0.049	
	187	(E)-β-Caryophyllene	0.049	
	188	Myrcene	0.042	
	189	α-Thujone	0.030	
	190	Borneol	0.016	
	191	β-Thujone	0.015	
	192	Viridiflorol	0.011	
23 [53]	193	α-Thujone	0.496	
	194	Fenchone	0.140	
	195	β-Thujone	0.091	
	196	Sabinene	0.040	
	197	α-pinene	0.033	
	198	Camphene	0.030	
	199	Camphor	0.025	
	200	Bornyl acetate	0.025	
	201	Limonene	0.019	
	202	4-Terpineol	0.018	
	203	α-Fenchene	0.015	
	204	Myrcene	0.014	
	205	p-Cymene	0.013	
24 [54]	206	1,8-cineole	0.399	
	207	linalool	0.194	
	208	α-Terpineol	0.040	
	209	β-pinene	0.027	
	210	α-pinene	0.026	
	211	camphene	0.025	
	212	γ-Terpinene	0.022	
	213	myrcene	0.019	
	214	limonene	0.014	
	215	camphor	0.014	
25 [55]	216	Thymol	0.577	
	217	p-Cymene	0.187	
	218	Carvacrol	0.028	
	219	Linalool	0.021	
	220	γ-Terpinene	0.019	
	221	Myrcene	0.015	
	222	(E)-Caryophyllene	0.014	
	223	Carvacrol methyl ether	0.013	
26 [56]	224	Bornylacetate	0.268	
	225	α-pinene	0.237	
	226	Camphene	0.119	
	227	Limonene	0.060	
	228	β-phellandrene	0.044	
	229	α-phellandrene	0.041	
	230	β-pinene	0.033	
	231	Camphor	0.026	
	232	2-cyclohexene-1-one	0.025	
	233	Caryophyllene	0.019	
	234	Borneol	0.015	
	235	Cycloheptane	0.012	
	236	1,3-benzenediamine	0.012	
27 [57]	237	β-phellandrene	0.160	
	238	Camphene	0.117	
	239	Geranial	0.093	
	240	Zingiberene	0.088	
	241	trans-Geraniol	0.070	
	242	α-pinene	0.048	
	243	β-pinene	0.039	
	244	β-Sesquiphellandrene	0.039	
	245	1-Terpinen-4-ol	0.037	
	246	β-Bisabolene	0.033	
	247	Myrtenal	0.028	
	248	α-Curcumene	0.024	
	249	Germacrene B	0.022	
	250	cis-p-Menth-2,8-dienol	0.018	
	251	Epiglobulol	0.013	
	252	Spathulenol	0.012	
	253	Cedr-8-ene	0.012	
a EOID: essential oil identifier; b ID: chemical compound identifier
• EOID=2, Acorus calamus: for some components, w is the average of two or three mass fractions (different places in Nepal)
• EOID=5, Eugenia caryophyllata: each w is the average of several mass fractions
• EOID=7, Lavandula angustifolia: each w is the average of two mass fractions
• EOID=8, Melissa officinalis: each w is the average of several mass fractions (different leaf positions and different harvest times)
• EOID=11, Mentha citrata: each w is the average of two mass fractions
• EOID=13, Mentha spicata: each w is the average of several mass fractions
• EOID=14, Ocimum basilicum: each w is the average of two mass fractions 
• EOID=18, Pelargonium graveolens: each w is the average of two mass fractions
• EOID=20, Pogostemon cablin: each w is the average of two mass fractions

Table 2S. Experimental and QSAR predicted  insecticidal activity for 27 selected plant essential oils. Test set members are denoted with ^ and prediction set members with ^^.
EOID	Plant source	Topical (Exp.)	Eq. 3	Eq. 4	Fumigant (Exp.)	Eq. 5	Eq. 6	
1	Abies siberica	1.9191	1.7071^	1.6904	1.0170	0.8765	0.9398	
2	Acorus calamus	1.9685	1.9244	1.6917	>1.9031	1.9062^	1.8886^	
3	Citrus aurantifolia	1.9777	2.0330	1.8635	0.7634	0.5767	0.6822	
4	Citrus limonum	1.7243	1.4175	1.5682	0.9823	1.3080	1.2728	
5	Eugenia caryophyllata	1.6021	1.3603	1.7542	>1.9031	1.7241	1.7812	
6	Juniperus virginiana	1.3802	1.2803	1.2391	>1.9031	1.8016	2.0178	
7	Lavandula angustifolia	1.7634	1.5007	1.7745	>1.9031	1.5725	1.9491	
8	Mellisa officinalis	1.3617	1.2693	1.4002	>1.9031	1.6676	1.7996	
9	Melaleuca quinquenervia	>2.0000	1.7730^^	1.6465^^	0.9685	1.6144^^	1.5701^^	
10	Mentha arvensis	1.5315	1.3455	1.5222^	1.4281	1.3697^	1.2956^	
11	Mentha citrata	1.3222	1.7216	1.3192	>1.9031	2.0250	1.8460	
12	Mentha pulegium	1.1139	1.0637	1.1007	0.6721	0.7540	0.7553	
13	Mentha spicata	1.3222	1.4880^^	1.0569^^	>1.9031	0.9028^^	1.8975^^	
14	Ocimum basilicum	1.1761	1.3522^	1.3438	1.7284	1.7678	1.4048	
15	Origanum compactum	1.1139	1.3319	1.2273	1.3385	1.5417	1.3857	
16	Origanum majorana	1.2304	1.2140	1.1407	0.9590	0.9715	1.0589	
17	Origanum vulgare	1.1139	1.3015	0.9271^	>1.9031	1.4941	1.3814	
18	Pelargonium graveolens	1.2788	1.5531	1.1977	>1.9031	1.9143	1.6668	
19	Pelargonium roseum	1.0000	1.1017	1.2386	>1.9031	1.8918	2.2534	
20	Pogostemon cablin	0.4771	0.5620	0.5191	>1.9031	1.9567	1.7092	
21	Rosmarinus officinalis	1.4472	1.5625	1.7555	0.9823	0.9257	1.0347	
22	Salvia officinalis	1.9138	1.8574	1.7565^	0.8976	1.2395	1.0911	
23	Thuja occidentalis	1.6232	1.6578	1.5258	0.7993	0.8692	0.8699	
24	Thymus mastichina	1.5185	1.6866^	1.8446	0.8633	1.1998^	1.1600^	
25	Thymus vulgaris	1.2553	1.3742	1.1775	0.9294	1.3989	1.3254	
26	Tsuga canadensis	1.9685	1.7353	1.8497	1.0531	0.9730	1.0251	
27	Zingiber officinale	1.9590	1.3484^^	1.0709^^	1.7259	1.3961^^	1.3278^^	

Table 3S. Squared correlation matrix for QSAR models. The last column includes the variance inflation factor for each descriptor.
Eq. 3	d1	d2	d3	VIF	
d1	1.00	0.04	4.12 10-4	1.00	
d2		1.00	0.24	1.08	
d3			1.00	1.06	

Eq. 4	d4	d5	d6	VIF	
d4	1.00	0.03	0.10	1.01	
d5		1.00	0.50	1.35	
d6			1.00	1.43	

Eq. 5	d7	d8	d9	VIF	
d7	1.00	0.11	0.07	1.04	
d8		1.00	0.02	1.03	
d9			1.00	1.02	

Eq. 6	d10	d11	d12	VIF	
d10	1.00	0.06	0.15	1.03	
d11		1.00	0.61	1.61	
d12			1.00	1.74	

Table 4S. Specificity of the established QSAR models in the training sets.
	Topical activity	Fumigant activity	
Eq. 3	, 	, 	
Eq. 4	, 	, 	
Eq. 5	, 	, 	
Eq. 6	, 	, 	

Table 5S. Mixture descriptor values involved in QSAR models of Eqs. 3-6.
EOID	d1	d2	d3	d4	d5	d6	d7	d8	d9	d10	d11	d12	
1	0.278	-0.1706538913	130.4808536442	0.0909090909	0.0502242237	36.4396437582	2.9046523874	0.1803282946	171979.8912730660	516.3504574631	2.3878268226	-175220.8983430760	
2	0.017	0.0887072501	613.1560080044	0.0000000000	0.1591866680	21.0443065656	3.9683811709	0.3159096737	223028.3982836200	-394.7169060060	13.3413829365	766780.7786464530	
3	0.227	-0.0771227253	469.2522574369	0.1904761905	0.0465218401	30.4915660109	1.9406946200	0.2342464976	211260.5279608370	57.2674536225	15.9511742724	1441089.0587109400	
4	1.016	-0.2604193366	8.0099966363	0.1428571429	0.0433150794	39.1744072207	3.6313697384	0.2029736438	180547.8979583330	84.0987519814	2.8629993161	-67841.5705852267	
5	0.057	0.1223239073	329.9849942515	0.0000000000	0.1389083381	22.8388188486	3.1231490472	0.2946835339	108301.0118007730	-286.7841919152	11.6997722453	622319.2397903850	
6	0.397	-0.1040869072	7.0896508343	0.6000000000	0.0322474406	37.5351825027	5.3230632004	0.2056554962	294289.9429964850	-484.1377318600	4.1752251512	-51976.4324303987	
7	0.476	-0.1636658879	68.4059505670	0.1000000000	0.0733714358	30.4857496054	3.8173993748	0.1888594009	92983.1565614431	200.1200015266	11.0820041021	167265.9327457430	
8	0.961	-0.0680801153	212.7066279849	0.2000000000	0.0488053015	40.8651829230	4.1903534113	0.2036533724	147886.2869674490	27.0653538482	7.9253312547	89796.1677768264	
9	0.442	-0.2798724714	39.2483150345	0.2222222222	0.0356229775	36.6140988652	3.9272882618	0.1988943373	114181.5665654570	5.9896126731	4.0154076674	-98596.9862721469	
10	0.059	-0.0355540018	65.8946895749	0.6666666667	0.0373584754	28.3661017410	2.7623646331	0.2292128369	58576.7135174802	-373.0803916129	13.5441745402	1128127.2066635800	
11	0.845	-0.2231952794	209.3293699224	0.2500000000	0.0880967936	35.2113253632	4.8227010964	0.1815202572	88244.5102600230	138.9173613561	9.2059748599	104126.2186867570	
12	1.924	-0.0305728490	409.5496313378	0.5000000000	0.0552084463	39.5621980999	2.6548490299	0.3192848483	417822.5854648990	-607.0047997788	11.3500925926	1407154.4197429100	
13	0.68	-0.0577193305	287.7599803898	0.7272727273	0.0609761952	34.0872537990	2.7475013053	0.2283767250	220659.0260527900	-74.4743769173	9.2450527812	208138.7622314500	
14	0.612	-0.1091691535	102.0090027937	0.1000000000	0.1490608019	28.4674260741	4.1367644229	0.2025686631	101326.5038743490	81.6209538794	8.6873350576	360104.5609731530	
15	0.209	-0.0600893299	58.7912816888	0.5000000000	0.0932666534	30.4170031294	3.0872656711	0.2666109198	117780.7036738840	19.7732149164	4.7880453515	71064.2382380216	
16	0.084	-0.0085171359	35.2566950344	0.2000000000	0.0545799554	46.0817477058	1.4474744102	0.2620106104	36681.3981494184	-60.3081556984	4.4126254190	284586.7352116570	
17	0.233	-0.0535667247	57.1392660521	0.8333333333	0.1110756324	26.4687943442	2.9872077268	0.2684703553	121154.4896006740	-39.3134316962	3.1351234568	-33461.0482318517	
18	0.169	-0.0654443496	175.8437429369	0.4285714286	0.0479351493	40.1908448269	2.9420702447	0.3518416033	110681.4140443010	-27.9239787969	4.6600625305	-79873.3680145409	
19	0.752	-0.0614128622	62.8305107657	0.5000000000	0.0390093502	38.9095093850	3.6268223998	0.2753698479	99429.6436046524	-14.5790656244	10.7041346355	83626.3117105055	
20	1.851	-0.0694005076	16.8218484785	0.7692307692	0.1052190729	38.6543380132	5.5546236390	0.2542743399	363548.6844965890	-141.4165958691	3.4940444939	-136682.9162625720	
21	0.411	-0.1582853206	97.4911251003	0.1538461538	0.0595863870	31.8400684132	2.8516778332	0.2001887401	180499.7188683650	346.1924383686	5.7284025961	162729.5944585990	
22	0.142	-0.2419389664	70.8164373854	0.2727272727	0.0469567950	30.9381360255	3.3054038724	0.1871318276	122237.5484731660	278.4462126508	5.5225106507	152696.7261958030	
23	0.084	-0.0856498910	184.5658038843	0.3846153846	0.0712904951	29.7258000735	2.3847786936	0.2522287482	213543.1829711540	450.0856941166	5.5773919269	184793.1618291090	
24	0.337	-0.2300609658	37.7881160113	0.1000000000	0.0380275007	34.5330787409	3.2280498153	0.1636846634	82143.0364230500	257.5837588439	3.6821495181	-35792.1927098712	
25	0.088	-0.0606422067	50.9285274000	0.6250000000	0.1096618077	25.8792078262	2.8795701464	0.2447602099	95230.8236846544	-46.6513210344	4.1919127929	96545.3634130035	
26	0.357	-0.2016949572	119.2320429675	0.1538461538	0.0545150485	30.4276770517	2.9174019510	0.2074489681	187490.9987670290	378.9719241211	4.5363609440	44763.3218131248	
27	0.681	-0.1615130907	33.8124001998	0.4117647059	0.0748385851	39.2634982309	3.7489004307	0.2171155784	193879.4603218710	87.7183417672	4.1199485072	6013.2376291700