Химия и химические технологии / 2. Теоретическая химия

A. S. Gotsulya, O. I. Panasenko, Ye. G. Knysh, T. S. Brytanova

Zaporozhye State Medical University

THE STUDY OF PHYSICAL AND CHEMICAL PROPERTIES OF 7-((3-THIO-4-R-1,2,4-TRIAZOLE-3-YL)METHYL)THEOPHYLLINE

Key words: 1,2,4-triazole, theophylline, UV-spectrophotometry, light absorption, intensity of absorption spectra.

It is well known that it`s necessary to examine the structure of derived substances and to establish a dependence between their structure and some physical and chemical constants to justify a detailed study of activity of the synthesized compounds in order to identify the direction of pharmacological action [1,3,4]. To the present, scientific publications cited data on research UV spectra of compounds, derivative 1,2,4-triazole, but their detailed study was carried out [3,4].

The aim was to study the UV spectra of aza-heterocyclic compounds, comprising 1,2,4-triazole and theophylline sintons in solvents of different polarity (water, 95% ethanol, 0.1 M and 1 M solutions of sodium hydroxide, 0.1 M and 1 M solutions of hydrochloric acid, 0.1 M and 1 M solutions of sulfuric acid, chloroform, propan-2-ol, acetonitrile and 1,4-dioxane) to establish the relationship between the chemical structure of the compounds and the nature of their electronic spectra.

The reason for choosing these solvents was determined with the following factors:

a) the ability to determine the presence of electrons transitions of bands shift, in solvents of different polarity (chloroform, propan-2-ol, acetonitrile, acetone, 1,4-dioxane in comparison with water and ethanol);

b) partial use of some solvents (chloroform, 95% ethanol, etc.) for the extraction substances out of biological objects and dosage forms);

c) necessity of a choice of solvents that form solutions of the highest optical density to use in future development of quality control methods;

d) the possibility of the formation of salts in solutions of hydrochloric acid and sodium hydroxide or oxonium salt in concentrated solutions of sulfuric acid and identify hydrolytic processes in alkaline or acidic medium;

e) calculation of dissociation constants if necessary;

f) the study of the effects of solute-solvent interaction to obtain the most complete information about the nature of the investigated electronic transition.

Materials and methods. All our used solvents and reagents were qualified «chemically pure». It was used spectrophotometer SPECORD 200-222U214 (Analytic Jena, Germany) for studying the UV spectra of the analyzed compounds and measuring the intensity. Measuring the absorption of solutions of these substances was performed in quartz cuvettes with a layer thickness of 10 mm. In the connection with the fact that we have synthesized substances that exhibit selective light absorption in the UV part of the spectrum, UV spectra were investigated at concentration of 1 mg%. Electronic spectra were studied in the range of 200 to 400 nm, the spectra schedule was built in the coordinates A=f (x).

Results and discussion. Electronic spectra in these solvents were measured to study the nature of the UV spectra of 7-((3-thio-4-phenyl-4H-1,2,4-triazole-5-yl) methyl)theophylline (I) 7-((3-thio-4-ethyl-4N-1,2,4-triazole-5-yl)methyl)theophyl-line (II) and 7-((3-thio-4-methyl-4H-1,2,4-triazole-5-yl)methyl)theophylline (III).

Table 1

№	Researched substance	Concentration of the solvent	λ, nm	A	E	lg E	Transitions of electrons
1	2	3	4	5	6	7	8
1	І	Water	206 258	1,2 0,620	44280 22880	4,65 4,36	π→π* π→π*
	ІІ	Water	206 252	1,083 0,705	34760 22630	4,54 4,36	π→π* π→π*
	ІІІ	Water	206 250	1,208 0,757	37090 23240	4,57 4,37	π→π* π→π*
2	І	95% ethanol	202 206 267	1,530 1,420 0,624	56500 52400 23030	4,75 4,72 4,36	π→π* π→π* π→π*
	ІІ	95% ethanol	203 258	1,371 0,604	44010 19390	4,65 4,28	π→π* π→π*
	ІІІ	95% ethanol	206 256	1,225 0,852	37610 26160	4,58 4,42	π→π* π→π*

Continuation of table1

1	2	3	4	5	6	7	8
3	І	0,1М NaOH	218 255	1,124 0,400	41480 15000	4,62 4,20	π→π* π→π*
	ІІ	0,1М NaOH	216 252	0,902 0,450	28350 14400	4,46 4,16	π→π* π→π*
	ІІІ	0,1М NaOH	205 256	1,212 0,775	37210 23800	4,57 4,38	π→π* π→π*
4	І	0,1М NaOH	222 253	1,542 0,250	56240 9230	4,75 3,96	π→π* π→π*
	ІІ	0,1М NaOH	225 252	1,399 0,320	44910 10270	4,63 4,01	π→π* π→π*
	ІІІ	0,1М NaOH	224 256	1,280 0,420	39760 12890	4,39 4,11	π→π* π→π*
5	І	0,1М HCl	206 257	1,354 0,651	49960 24022	4,69 4,38	π→π* π→π*
	ІІ	0,1М HCl	206 252	1,094 0,696	35120 22340	4,55 4,35	π→π* π→π*
	ІІІ	0,1М HCl	206 250	0,855 0,499	26750 15320	4,42 4,19	π→π* π→π*
6	І	0,1М HCl	206 257	1,326 0,024	43930 23030	4,69 4,36	π→π* π→π*
	ІІ	0,1М HCl	206 252	0,719 0,335	23080 10750	4,36 4,03	π→π* π→π*
	ІІІ	0,1М HCl	208 251	1,047 0,761	32140 23360	4,51 4,37	π→π* π→π*
7	І	0,1М H2SO4	206 258	1,320 0,611	48710 22550	4,64 4,35	π→π* π→π*
	ІІ	0,1М H2SO4	205 252	0,841 0,456	26990 15000	4,43 4,17	π→π* π→π*
	ІІІ	0,1М H2SO4	206 251	1,186 0,751	36410 23055	4,56 4,36	π→π* π→π*
8	І	1М H2SO4	204 263	1,240 0,478	45760 17640	4,66 4,25	π→π* π→π*
	ІІ	1М H2SO4	206 250	1,462 0,899	46930 28900	4,67 4,46	π→π* π→π*
	ІІІ	1М H2SO4	206 251	1,288 0,873	39540 26800	4,60 4,43	π→π* π→π*
9	І	Chloroform	270	0,733	27050	4,43	π→π*
	ІІ	Chloroform	510 532	0,04 0,03	12840 9210	4,11 3,97	π→π* π→π*
	ІІІ	Chloroform	262	0,878	29630	4,47	π→π*
10	І	Propane-2-ol	208 268	1,444 0,794	53280 29300	4,73 4,46	π→π* π→π*
	ІІ	Propane-2-ol	207 259	0,938 0,739	30110 23720	4,48 4,38	π→π* π→π*
	ІІІ	Propane-2-ol	207 257	1,314 1,024	40340 31440	4,04 4,49	π→π* π→π*

Continuation of table1

1	2	3	4	5	6	7	8
11	І	Acetonitrile	235 270	0,579 0,576	21360 21250	4,33 4,33	π→π* π→π*
	ІІ	Acetonitrile	234 270	0,694 0,62`0	22280 19900	4,35 4,30	π→π* π→π*
	ІІІ	Acetonitrile	235 272	0,720 0,668	22100 20510	4,34 4,31	π→π* π→π*
12	І	1,4-dioxane	279	0,339	12510	4,09	π→π*
	ІІ	1,4-dioxane	279	0,155	4980	3,70	π→π*
	ІІІ	1,4-dioxane	272	0,599	18400	4,27	π→π*

These data in table 1 show that the UV spectra of the compounds in water, 95% ethanol; 0.1 M and 1 M solutions of NaOH, HCl, H₂SO₄,propan-2-ol and acetonitrile are characterized with two absorption bands. The first band exhibits maxima at 203-235 nm, and the second - in the range of 250-272 nm. Electronic band of all three compounds we have studied in chloroform and 1,4-dioxane has only one band with a maxima in the range of 262-279 nm. This is due to the fact that the omission capacity of chloroform and 1,4-dioxane starts from 276 nm (chloroform) and from 277 nm (1,4-dioxane).

Each of the three studied molecules is consisted of two fragments. The first - purine and the second – 1,2,4-triazole cycle. Significant opportunity of resonance manifest for purine molecules which formally contain four double bonds. The spectra of neutral purine solutions are characterized with two broad intense bands: at <220 nm (E> 3000) and at 263 nm (E> 8000). The shortwave band of purine corresponds to π → π* ¹L_a transition type of electrons, and the band at 263 nm corresponds to the permitted ¹L_b.transition type of electrons.

This purine band at 260 nm is complex, and the transition of electrons, which corresponds to it, is caused with longitudinal polarization of purine series [8].

Purine radical is connected to 1,2,4-triazole cycle with methylene group. As you know UV spectrum of 1,2,4-triazoles in aqueous solution is characterized with one band at 187 nm [8]. It is due to the fact that it has not homocyclic conjugation. Therefore, a characteristic feature of the absorption spectra of 1,2,4-triazole is the absence of bands, which are caused with the transition from lone electron heteroatoms orbitals on π-orbital cycle. In this case, the lone electron heteroatoms orbital has pronounced s-character in comparison with similar orbital six-membered cycles due to lower valence angles in the first [5].

As methylene fragment separates purine cycle from 1,2,4- triazole, in this case p-π-conjugation cannot be between them. There are only two bands on the total electronic spectrum of the compounds, because maximum of the UV absorption band is in near UV (187 nm) (Table 1).

Conclusions

1. UV spectra of 7-((3-thio-4-methyl-1,2,4-triazole-5-yl) methyl)theophylline, 7-((3-thio-4-ethyl-1,2,4-triazole-5-yl)methyl)theophylline and 7-((3-thio-4-phenyl-1,2,4-triazole-5-yl)methyl)theophylline have studied in neutral, acidic and alkaline solvents.

2. It is established that the electronic spectra of the compounds are characterized with maxima in the short waved (203-235 nm) and median waved (250-272 nm) parts of UV spectrum.

3. Absorption maxima of the analyzed compounds are caused with permitted π → π * electrons transitions according to ¹L_a and ¹L_b due to the presence of methylene fragment in the molecules of analyzed compounds which separates purine cycle from 1,2,4-triazole.

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