Solvatochromism and Thermochromism of Fluconazole: An Experimental and Theoretical Study

Olivares, Fernando G.; Lazcano, Francisco G.; Castillo, Marcelo O.; Barúa, Maria G.; Escalada, Juan P.; Vitorino, Graciela Pinto

doi:10.21577/0103-5053.20230050

Fernando G. Olivares ^**e-mail: folivares@uarg.unpa.edu.ar

contributed to the study

conception

design

Conceptualization of the research

Quality control

preparation of experimental samples (resources)

Solvatochromic experimental data collection

data curation and formal analysis

Theoretical calculation data collection

data curation and formal analysis

Thermochromic techniques

The UV-Vis spectrum was interpreted

The validation of the data obtained

the funding acquisitions

The first draft of the manuscript was written

commented on previous versions of the manuscript

read and approved the final manuscript

Instituto de Tecnología Aplicada, Unidad Académica Río Gallegos, Universidad Nacional de la Patagonia Austral (ITA UARG UNPA), Av. Piloto “Lero” Rivera y Av. Gdor. Gregores S/N, Río Gallegos, Santa Cruz, 9400, Argentina

https://orcid.org/0000-0001-8711-0779

Francisco G. Lazcano

contributed to the study

conception

design

Quality control

preparation of experimental samples (resources)

commented on previous versions of the manuscript

read and approved the final manuscript

Instituto de Tecnología Aplicada, Unidad Académica Río Gallegos, Universidad Nacional de la Patagonia Austral (ITA UARG UNPA), Av. Piloto “Lero” Rivera y Av. Gdor. Gregores S/N, Río Gallegos, Santa Cruz, 9400, Argentina

Marcelo O. Castillo

contributed to the study

conception

design

Theoretical calculation data collection

data curation and formal analysis

commented on previous versions of the manuscript

read and approved the final manuscript

Grupo Química Medicinal, Centro Regional de Investigación y Desarrollo Científico Tecnológico, Facultad de Ciencias Naturales y Ciencias de la Salud, Universidad Nacional de la Patagonia San Juan Bosco (GQM-CRIDECIT FCNyCS UNPSJB), km 4, Comodoro Rivadavia, Chubut, 9000, Argentina

Maria G. Barúa

contributed to the study

conception

design

Quality control

preparation of experimental samples (resources)

Solvatochromic experimental data collection

data curation and formal analysis

Thermochromic techniques

The UV-Vis spectrum was interpreted

commented on previous versions of the manuscript

read and approved the final manuscript

Instituto de Tecnología Aplicada, Unidad Académica Río Gallegos, Universidad Nacional de la Patagonia Austral (ITA UARG UNPA), Av. Piloto “Lero” Rivera y Av. Gdor. Gregores S/N, Río Gallegos, Santa Cruz, 9400, Argentina

Juan P. Escalada

contributed to the study

conception

design

Conceptualization of the research

Solvatochromic experimental data collection

data curation and formal analysis

The UV-Vis spectrum was interpreted

The validation of the data obtained

the funding acquisitions

commented on previous versions of the manuscript

read and approved the final manuscript

Instituto de Tecnología Aplicada, Unidad Académica Río Gallegos, Universidad Nacional de la Patagonia Austral (ITA UARG UNPA), Av. Piloto “Lero” Rivera y Av. Gdor. Gregores S/N, Río Gallegos, Santa Cruz, 9400, Argentina

Graciela Pinto Vitorino

contributed to the study

conception

design

Conceptualization of the research

Solvatochromic experimental data collection

data curation and formal analysis

Theoretical calculation data collection

data curation and formal analysis

The UV-Vis spectrum was interpreted

The validation of the data obtained

the funding acquisitions

commented on previous versions of the manuscript

read and approved the final manuscript

Grupo Química Medicinal, Centro Regional de Investigación y Desarrollo Científico Tecnológico, Facultad de Ciencias Naturales y Ciencias de la Salud, Universidad Nacional de la Patagonia San Juan Bosco (GQM-CRIDECIT FCNyCS UNPSJB), km 4, Comodoro Rivadavia, Chubut, 9000, Argentina

*e-mail: folivares@uarg.unpa.edu.ar

Editor handled this article: Paula Homem-de-Mello (Associate)

Solvent	µD / Debye	E_r	n_D	h / (10^-3 Pa s)	Kamlet-Taft			Catalán				Laurence
Solvent	µD / Debye	E_r	n_D	h / (10^-3 Pa s)	π^*	α	β	SP	SdP	SA	SB	DI	ES	α₁	β₁
Cy	0.00	2.02	1.4262	0.89	0.00	0.00	0.00	0.683	0.000	0,000	0.073	0.78	0.00	0.00	0.00
Tet	0.00	2.24	1.4602	0.90	0.21	0.00	0,10	0.768	0.000	0.000	0.044	0.82	0.10	0.00	0.00
Ben	0.00	2.27	1.5011	0.60	0,55	0.00	0,10	0.793	0.270	0.000	0.124	0.87	0.23	0.00	0.14
DE	1.15	4.20	1.3524	0.22	0.27	0.00	0.47	0.617	0.385	0.000	0.562	0.68	0.26	0.00	0.58
DCM	1.36	8.93	1.4242	0.41	0.79	0.04	-0.01	0.761	0.769	0.040	0.178	0.78	0.60	0.10	0.00
AcN	3.92	35.94	1.3441	0.37	0.75	0.19	0.31	0.645	0.974	0.044	0.286	0.67	0.84	0.23	0.37
DMSO	3.98	46.45	1.4793	1.99	1,00	0.00	0.76	0.830	1.000	0.072	0.647	0.84	1.00	0.00	0.71
2PrOH	1.56	19.92	1.3772	2.04	0.48	0.76	0.84	0.633	0.808	0.283	0.830	0.71	0.77	0.53	0.68
EtOH	1.66	24.55	1.3614	1.07	0.54	0.83	0.77	0.633	0.783	0.400	0.658	0.69	0.80	0.75	0.62
MeOH	1.70	32.66	1.3284	0.54	0.60	0.93	0.62	0.608	0.904	0.605	0.545	0.64	0.84	1.00	0.54
Water	1.85	78.36	1.3330	0.89	1.09	1.17	0.47	0.681	0.997	1.062	0.025	0.65	0.89	1.54	0.37

Bond length / Å					Bond angle and dihedral angle / degree
Parameter	B3LYP		CAM B3LYP		Parameter	B3LYP		CAM B3LYP
Parameter	I	II	I	II	Parameter	I	II	I	II
C4-H9	1.084	1.084	1.083	1.083	C5-C10-O31	112.92	111.09	112.45	110.99
C10-O31	1.422	1.422	1.415	1.415	C14-C10-O31	103.93	105.31	104.15	105.39
O31-H32	0.977	0.977	0.975	0.979	C4-C5-C6	115.57	116.10	115.73	116.27
N22-N27	1.364	1.364	1.355	1.354	C5-C6-C1	123.80	124.09	123.90	124.08
N17-N29	1.365	1.365	1.356	1.355	C5-C4-C3	122.75	122.17	122.53	122.04
C24-N27	1.327	1.327	1.319	1.321	C3-C2-C1	122.04	122.29	122.13	122.37
C18-N17	1.355	1.355	1.348	1.347	H12-C11-H13	109.05	10911	109.07	109.17
C11-N22	1.452	1.452	1.447	1.450	H15-C14-H16	108.23	109.26	108.22	109.33
C24-N28	1.361	1.361	1.356	1.353	C10-C5-C6-C1	179.08	178.44	179.06	178.35
C14-N17	1.453	1.453	1.448	1.446	C10-C5-C4-C3	-178.70	-178.43	-178.72	-178.32
C4-C5	1.407	1.407	1.400	1.395	C11-N22-N27-C24	-179.06	-179.38	-178.34	-178.87
C5-C6	1.402	1.402	1.395	1.391	C11-N22-C23-N28	179.18	179.54	178.36	178.95
C3-C4	1.395	1.395	1.390	1.391	C14-N17-N29-C19	178.29	-178.99	178.32	-178.28
C3-C2	1.388	1.388	1.383	1.383	C14-N17-C18-N30	-178.07	178.95	-178.10	178.14
C2-C1	1.387	1.387	1.382	1.384	C6-C5-C10-C14	149.97	-65.29	154.64	-65.58
C1-C6	1.391	1.391	1.384	1.381	C10-C5-C6-F33	-0.09	-1.50	-0.10	-1.58
C14-H16	1.091	1.091	1.090	1.090	C6-C5-C10-O31	32.37	177.57	37.00	177.44
C11-H13	1.094	1.090	1.093	1.090	C10-C14-N17-N29	121.91	123.27	105.30	104.97
					C10-C11-N22-N27	67.56	69.87	57.22	56.85
					C10-C14-N17-C18	-60.42	-59.00	-73.30	-72.61
					C10-C11-N22-C23	-111.22	-107.92	-122.00	-121.62
					C5-C10-C14-N17	-53.92	-54.40	-57.08	-56.51
					C5-C10-C11-N22	62.92	63.47	57.40	56.34

Solvent	Experimental
Solvent	λ₂₆₁ / nm	$\bar{v}$ ₂₆₁ / cm^-1	ε₂₆₁ / (cm^-1 M^-1)	λ₂₆₆ / nm	$\bar{v}$ ₂₆₆ / cm^-1	ε₂₆₆ / (cm^-1 M^-1)
Diethyl ether	260.3	38.419	671.9	266.8	37.487	650.6
Dichloromethane	260.3	38.419	617.5	266.8	37.487	539.9
Acetonitrile	260.2	38.429	661.1	266.7	37.492	527.4
Dimethyl sulfoxide	261.0	38.313	569.1	267.4	37.392	536.0
2-Propanol	260.8	38.336	582.3	267.0	37.451	571.7
Ethanol	260.3	38.422	639.7	266.8	37.484	603.8
Methanol	260.3	38.422	659.6	266.5	37.523	637.2
Buffer pH 7.4	260.0	38.461	649.5	266.3	37.554	609.4

Kamlet and Taft
Wavelength / nm	A₀		s	a	b	R²	F
261	38,480.6 ± 48.6		-45.7 ± 51.3	76.2 ± 31.3	-158.2 ± 53.7	0.720	0.133
			16%	27%	57%
266	37,540.4 ± 31.4		-44.0 ± 33.2	95.5 ± 20.3	-138.1 ± 34.8	0.870	0.031
			16%	34%	50%
Catalán
Wavelength / nm	A₀	c_SP	d_SdP	a_SA	b_SB	R²	F
261	38,737.2 ± 98.2	-342.3 ± 150.7	-43.1 ± 60.3	11.6 ± 34.0	-152.5 ± 38.0	0.898	0.076
		62%	8%	2%	28%
266	37,774.5 ± 48.6	-334.4 ± 74.5	-31.8 ± 29.8	46.5 ± 16.8	-113.5 ± 18.8	0.972	0.011
		65%	6%	8%	21%
Laurance
Wavelength / nm	A₀	di	e	a₁	b₁	R²	F
261	38,776.9 ± 188.4	-427.3 ± 278.1	-30.7 ± 72.4	16.6 ± 37.6	-118.2 ± 51.9	0.840	0.144
		72%	5%	3%	20%
266	37,780.2 ± 60.6	-346.9 ± 89.4	-39.7 ± 23.3	41.9 ± 12.1	-89.0 ± 16.7	0.982	0.006
		67%	8%	8%	17%

Solvent	Conformer I						Conformer II
	B3LYP			CAMB3LYP			B3LYP			CAMB3LYP
	λ_max / nm	${\bar{v}}_{max}$ / cm^-1	f	λ_max / nm	${\bar{v}}_{max}$ / cm^-1	f	λ_max / nm	${\bar{v}}_{max}$ / cm^-1	f	λ_max / nm	${\bar{v}}_{max}$ / cm^-1	f
Cy	236.4	42.301	0.021	228.2	43.829	0.021	234.8	42.588	0.014	226.9	44.084	0.013
Tet	236.4	42.310	0.021	228.1	43.835	0.021	234.8	42.591	0.014	226.8	44.086	0.013
Ben	236.4	42.308	0.022	228.1	43.833	0.022	234.8	42.590	0.014	226.9	44.082	0.013
DE	236.0	42.373	0.017	227.9	43.889	0.019	234.6	42.628	0.013	226.7	44.115	0.012
DCM	235.9	42.394	0.019	227.8	43.904	0.019	234.6	42.637	0.013	226.7	44.119	0.013
AcN	235.7	42.423	0.018	227.6	43.931	0.018	234.5	42.651	0.012	226.6	44.133	0.012
DMSO	235.7	42,416	0,018	227.7	43.923	0.018	234.5	42.646	0.013	226.6	44.127	0.012
EtOH	235.6	42.418	0.018	227.7	43.927	0.018	234.5	42.650	0.012	226.6	44.129	0.012
MeOH	235.7	42.423	0.017	227.6	43.933	0.017	234.5	42.653	0.012	226.6	44.133	0.012
Water	235.7	42.427	0.017	227.6	43.935	0.017	234.4	42.55	0.012	226.6	44.135	0.012

Kamlet and Taft	A₀		s	a	b	R^2e	F ^f
B3LYP^a a B3LYP: functional Becke, 3-parameter, Lee-Yang-Parr;	42,366.9 ± 20.8^c c n = 7;		38.8 ± 22.8	17.3 ± 13.5	16.5 ± 24.3	0.709	0.242
			53%	24%	23%
	42,303.1 ± 20.3^d d n = 10;		77.1 ± 33.3	20.8 ± 26.6	69.9 ± 41.0	0.782	0.021
			46%	12%	42%
CAMB3LYP^b b CAM B3LYP: hybrid exchange correlation Coulomb Attenuated Method - Becke, 3-parameter, Lee-Yang-Parr;	43,883.3 ± 18.2^c c n = 7;		30.4 ± 19.9	17.00 ± 11.8	15.1 ± 21.2	0.712	0.238
			49%	27%	24%
	43,829.8 ± 17.2^d d n = 10;		62.3 ± 28.2	20.1 ± 22.5	60.0 ± 34.8	0.783	0.021
			44%	14%	42%
Catalán	A₀	c_SP	d_SdP	a_SA	b_SB	R²	F ^f
B3LYP	42,375.6 ± 15.7^c c n = 7;	-72.0 ± 24.4	92.0 ± 9.8	7.4 ± 5.5	13.0 ± 7.2	0.987	0.026
		39%	50%	4%	7%
	42,381.0 ± 42.7^d d n = 10;	-111.1 ± 57.4	112.5 ± 14.1	5.7 ± 15.4	21.4 ± 19.5	0.973	0.0004
		44%	45%	2%	9%
CAMB3LYP	43,897.4 ± 12.0^c c n = 7;	-74.9 ± 18.6	79.3 ± 7.4	8.1 ± 4.2	13.2 ± 5.5	0.99	0.020
		43%	45%	5%	7%
	43,902.7 ± 34.6^d d n = 10;	-104.4 ± 46.5	93.4 ± 11.4	7.0 ± 12.5	19.1 ± 15.8	0.976	0.0003
		47%	42%	3%	8%
Laurence	A₀	di	e	a₁	b₁	R²	F ^f
B3LYP	42,427.5 ± 12.0^c c n = 7;	-106.0 ± 17.6	82.5 ± 4.6	-1.6 ± 2.4	-6.0 ± 3.5	0.997	0.006
		54%	42%	1%	3%
	42,500.2 ± 48.5^d d n = 10;	-247.0 ± 60.6	124.4 ± 14.7	-17.0 ± 10.1	-1.6 ± 18.0	0.979	0.0002
		63%	32%	4%	1%
CAMB3LYP	43,944.0 ± 9.9^c c n = 7;	-105.8 ± 14.6	70.3 ± 3.8	-1.0 ± 2.0	-2.3 ± 2.9	0.997	0.006
		59%	39%	1%	1%
	44,001.4 ± 37.0^d d n = 10;	-215.7 ± 46.3	102.2 ± 11.6	-12.9 ± 7.7	0.8 ± 13.7	0.983	0.0001
		65%	31%	4%	0%

Kamlet and Taft	A₀		s	a	b	R^2e	F ^f
B3LYP^a a B3LYP: functional Becke, 3-parameter, Lee-Yang-Parr;	42,625.5 ± 9.9^c c n = 7;		16.4 ± 10.8	11.1 ± 6.4	6.5 ± 11.5	0.740	0.207
			48%	33%	19%
	42,588.9 ± 11.2^d d n = 10;		38.6 ± 18.4	13.0 ± 14.7	36.9 ± 22.7	0.766	0.025
			44%	15%	41%
CAMB3LYP^b b CAM B3LYP: hybrid exchange correlation Coulomb Attenuated Method - Becke, 3-parameter, Lee-Yang-Parr;	44,112.8 ± 8.0^c c n = 7;		11.4 ± 8.7	8.2 ± 5.2	4.8 ± 9.3	0.696	0.257
			47%	34%	19%
	44,084.3 ± 9.1^d d n = 10;		28.1 ± 15.0	10.0 ± 12.0	28.8 ± 18.3	0.740	0.034
			42%	15%	43%
Catalán	A₀	c_SP	d_SdP	a_SA	b_SB	R²	F
B3LYP	42,635.9 ± 7.0^c c n = 7;	-44.8 ± 10.7	43.4 ± 4.3	5.7 ± 2.4	5.7 ± 3.1	0.990	0.020
		45%	44%	6%	5%
	42,639.1 ± 24.3^d d n = 10;	-72.0 ± 32.8	58.5 ± 8.0	4.1 ± 8.8	11.4 ± 11.1	0.970	0.0005
		49%	40%	3%	8%
CAMB3LYP	44,125.8 ± 5.8^c c n = 7;	-41.4 ± 9.1	32.7 ± 3.6	3.4 ± 2.0	3.0 ± 2.7	0.987	0.026
		51%	41%	4%	4%
	44,130.3 ± 21.1^d d n = 10;	-65.9 ± 28.4	44.8 ± 7.0	2.0 ± 7.6	7.5 ± 9.6	0.961	0.001
		55%	37%	2%	6%
Laurence	A₀	di	e	a₁	b₁	R²	F
B3LYP	42,660.6 ± 5.8^c c n = 7;	-60.4 ± 8.5	38.1 ± 2.2	0.7 ± 1.1	-2.7 ± 1.7	0.997	0.006
		59%	37%	1%	3%
	42,704.4 ± 28.8^d d n = 10;	-145.3 ± 36.0	63.3 ± 8.8	-8.7 ± 6.0	-0.1 ± 10.7	0.974	0.0004
		67%	29%	4%	0%
CAMB3LYP	44,148.3 ± 5.2^c c n = 7;	-59.4 ± 7.7	28.9 ± 2.0	-0.7 ± 1.0	-1.1 ± 1.5	0.996	0.009
		66%	32%	1%	1%
	44,183.6 ± 21.5^d d n = 10;	-125.3 ± 27.0	47.2 ± 6.5	-7.8 ± 4.5	0.3 ± 8.0	0.975	0.0003
		69%	26%	4%	1%

[1] *e-mail: folivares@uarg.unpa.edu.ar

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Solvatochromism and Thermochromism of Fluconazole: An Experimental and Theoretical Study