RU2574883C2 - Radiopaque substance (versions) - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: described is radiopaque substance, based on hexanuclear rhenium cluster complexes, expressed by formulae: [{Re₆Q₈}L¹ _nL² _mX_6-n-m]^q and [{Re₆Q₈}L¹ _nL² _mY_6-n-m]^q, containing octahedral cluster nucleus {Re₆Q₈}, in which Q is S or Se; where L¹ and L² stand for pyridine-containing ligands, which are bound with cluster nucleus by means of Re-N bond, where X stands for residues of organic and inorganic monobasic acids and Y stands for residues of organic and inorganic dibasic acids. Technical result consists in reduction of radiopaque substance toxicity and, as a result, in reduction of probability of development of contrast-inducing nephropathy. Unique peculiarity of invention consists in electroneutrality and presence of biologically safe ligand surrounding with hydrophilic non-ionogenic functional groups, which provides iso-osmolarity to physiological fluids.

EFFECT: possibility of reducing introduced doses of preparation.

2 cl, 4 ex

Description

The invention relates to medicine, in particular to radiology, and can be used as a radiopaque in radiological studies of various organs.

The contrast agents used in the X-ray diagnostics are used to improve the visualization of internal organs and anatomical structures in radiation research methods, for example, in X-ray computed tomography and radiography. Radiopositive drugs used in most cases, as a rule, contain iodine. According to their physicochemical properties, they distinguish between ionic and nonionic contrast agents. Initially, ionic iodine-containing contrast agents were developed, which are currently still used in X-ray diagnostics. Some of the disadvantages of ionic preparations due to the dissociation of molecules, electrical charge of particles and hypertonicity are sometimes manifested in the development of adverse reactions such as nausea, vomiting, urticaria, etc. In non-ionic contrast preparations, iodine is bound by covalent bonds, which significantly reduces the risk of complications. To date, non-ionic drugs, such as Ultravist, Visipack, Omnipack, are most widely used. They are widely used in those methods of radiation diagnostics that require a large amount of contrast medium and high rates of its administration (computed tomography, digital subtraction angiography (DSA).

Rhenium cluster complexes of the type [{Re ₆ Q ₈ } L ₆ ], where Q - S, Se; a L - mono- or polydentate organic or inorganic ligand, are extremely promising radiopaque media due to the high electron density of the cluster core and, as a consequence, high x-ray contrast.

In the work “A new class of radiopaque compounds based on octahedral metal-cluster complexes”, authors: A.A. Krasilnikova, M.A. Shestopalov, K.A. Brylev, O.P. Khripko, V.Yu. Marchenko, I.A. Kirilova, L.V. Shestopalova (Materials of the II International Forum “Innovations in medicine: main problems and solutions. High-tech medicine as an element of an innovative economy”) the toxicity of the cluster complex composition Na _1-6-x H _x [{Re ₆ Se ₈ } (P ( CH ₂ CH ₂ COO) ₃ ) ₆ ] and demonstrated its x-ray contrast using computed tomography in rats. Low toxicity was shown with a single injection of a solution of a cluster complex in doses of 100, 200, 400, 500 and 800 mg / kg of body weight. The negative effect observed on the condition of the renal tubules and liver vessels can be explained by the high degree of ionicity and osmolarity of this compound, as well as the toxic effect of the released phosphines.

The closest solution to the claimed invention is US patent 5804161 (A) (priority from 1996/08/26, IPC A61K 49/04), where hexayuclear cluster complexes [{M ₆ Q ₈ } B _n L _{6 are} proposed as a radiopaque medium _-n ] ^x , where M is Rh or Re; Q is O, S, Se or Te; B - monovalent non-bridging atoms or molecules; a L - phosphine PR ₃ groups containing one or more amino or hydroxy groups. One of the important disadvantages of this invention is the presence of organic phosphines. With the introduction of phosphine-containing cluster complexes into the body, the release of free organophosphorus compounds due to hydrolysis is possible. It is known that such organophosphorus compounds are extremely toxic substances. When ingested, they cause irreversible cholinesterase inhibition processes, as a result of which the enzyme loses its ability to hydrolyze acetylchaline, which has a muscarinic-like and nicotine-like effect. Through the activation of cholinergic systems, these substances affect many organs, permanently disrupting their functions even with a favorable outcome of poisoning. [Guide for emergency doctors // edited by V.A. Mikhailovich, A.G. Miroshnechenko - 4th ed., Rev. and add. - St. Petersburg: Publishing House SPbMAPO, 2007, 805 pp.]

The objective of the invention is to create a safe radiopaque substance based on octahedral cluster complexes of rhenium, which has high chemical resistance and a high degree of water solubility, which leads to its high diagnostic efficiency, low toxicity and good tolerance.

The problem is solved by replacing highly toxic phosphines with safer and physiologically compatible derivatives of nicotinic or isonicotinic acids, as well as pyridinaldehyde derivatives. According to the present invention, two variants of compounds based on hexa-nuclear rhenium cluster complexes are described as radiopaque substances, described by the following formulas: option 1 [{Re ₆ Q ₈ } L ¹ _n L ² _m X _6-nm ] ^q and option 2 [{Re ₆ Q ₈ } L ¹ _n L ² _m Y _6-nm ] ^q . These complexes contain an octahedral cluster core {Re ₆ Q ₈ }, in which Q is S or Se; L ¹ and L ² are organic pyridine-containing ligands that are linked to the cluster core via a Re-N bond; in option 1: X denotes residues of organic and inorganic dibasic acids, in option 2: Y denotes residues of organic and inorganic dibasic acids.

Option 1 is preferred.

Option 1. The problem is solved by creating a radiopaque substance expressed by the formula [{Re ₆ Q ₈ } L ¹ _n L ² _m X _6-nm ] ^q , containing the octahedral cluster core {Re ₆ Q ₈ }, where: Q - S or Se; n is 0, 1, 2, 3, 4, 5, or 6; m is 0, 1, 2, 3, 4, 5, or 6; n + m = 0, 1, 2, 3, 4, 5, or 6; q = 4-, 3-, 2-, 1-, 0, 1+ or 2+; X is a singly charged anionic ligand of organic or inorganic nature and can be selected from the series:

, $$N{O}_3^{-}$$

, SH^-, $$C{F}_3^{-}$$

, $$H_{2}P{O}_4^{-}$$

, $$H_{2}P{O}_3^{-}$$

, $$H_{2}P{O}_2^{-}$$

, HRCOO^- или $$RS{O}_3^{-}$$

, где R обозначает предельный или непредельный алифатический или ароматический остаток, в том числе содержащий фтор, состоящий из: -Н, -СН₃, -CH₂CH₃, -СН₂СН₂СН₃, -СН(СН₃)₂, -СН₂СН₂СН₂СН₃, -СН₂СН(СН₃)₂, -СН(СН₃)СН₂СН₃, -С(СН₃)₃, -С₆Н₅, -C₆H₄CH₃, -C₅H₄N, -CF₃, -CF₂CF₃, -CF₂CF₂CF₃, -CF(CF₃)₂, -CF₂CF₂CF₂CF₃, -CF₂CF(CF₃)₂, -CF(CF₃)CF₂CF₃, -C(CF₃)₃, -C₆F₅.F ^- , Cl ^- , Br ^- , I ^- , CN ^- , SCN ^- , SeCN ^- , OH ^- , NO ^- , $$N{O}_2^{-}$$

, $$N{O}_3^{-}$$

, SH ^- , $$C{F}_3^{-}$$

, $$H_{2}P{O}_{\mathrm{four}}^{-}$$

, $$H_{2}P{O}_3^{-}$$

, $$H_{2}P{O}_2^{-}$$

HRCOO ^- or $$RS{O}_3^{-}$$

where R denotes a limiting or unsaturated aliphatic or aromatic residue, including containing fluorine, consisting of: —H, —CH ₃ , —CH ₂ CH ₃ , —CH ₂ CH ₂ CH ₂ , —CH (CH ₃ ) ₂ , -CH ₂ CH ₂ CH ₂ CH ₃ , -CH ₂ CH (CH ₃ ) ₂ , -CH (CH ₃ ) CH ₂ CH ₃ , -C (CH ₃ ) ₃ , -C ₆ H ₅ , -C ₆ H ₄ CH ₃ , -C ₅ H ₄ N, -CF ₃ , -CF ₂ CF ₃ , -CF ₂ CF ₂ CF ₃ , -CF (CF ₃ ) ₂ , -CF ₂ CF ₂ CF ₂ CF ₃ , -CF ₂ CF (CF ₃ ) ₂ , -CF (CF ₃ ) CF ₂ CF ₃ , -C (CF ₃ ) ₃ , -C ₆ F ₅ .

L ¹ and L ² are pyridine-containing ligands that are linked to the cluster core via a Re-N bond and are selected from a number of nicotinic or isonicotinic acid derivatives containing, in the composition of the R1 group: hydroxy- or amino- or diethanolamino-propane-2 , 3-diol-1-amino, or propan-1,3-diol-2-amino, or 2-hydroxymethyl-propan-1,3-diol-2-amino, or hexane-2,3,4 5,6-pentaol-1-hydroxy- or 6- (4,6-bis- (hexane-2,3,4,5,6-pentaol-1-hydroxy) -1,3,5-triazine) - hexane-2,3,4,5, pentaol-1-hydroxy groups; or selected from a series of derivatives of 4-pyridinaldehyde or 3-pyridinaldehyde containing in the group R2: tris- (hydroxymethyl) methyl, or 2,3-dihydroxypropyl or bis- (hydroxymethyl) methyl groups.

Example 1, in which L ¹ and L ² are derivatives of nicotinic or isonicotinic acids containing R1 groups:

или

or

In this case, R1 means:

hydroxy groups

-OH;

or amino groups

- NH ₂ ;

or diethanolamino groups (-N (CH ₂ CH ₂ OH) ₂ ):

or propane-2,3-diol-1-amino groups (-NHCH ₂ CH (OH) CH ₂ OH):

or propane-1,3-diol-2-amino groups (-NHCH (CH ₂ OH) ₂ ):

or 2-hydroxymethyl-propan-1,3-diol-2-amino groups (-NHC (CH ₂ OH) ₃ ):

or hexane-2,3,4,5,6-pentaol-1-hydroxy groups

(-OCH ₂ CH (OH) CH (OH) CH (OH) CH (OH) CH ₂ OH):

or 6- (4,6-bis- (hexane-2,3,4,5,6-pentaol-1-hydroxy) -1,3,5-triazine) -hexane-2,3,4,5, - pentaol-1-hydroxy groups

(-OCH ₂ CH (OH) CH (OH) CH (OH) CH (OH) CH ₂ O [C ₃ N ₃ ] (OCH ₂ CH (OH) CH (OH) CH (OH) CH (OH) CH ₂ OH) ₂ ):

The proposed substance can be obtained as follows.

Synthesis details of the octahedral cluster complexes of the composition [{Re ₆ Q ₈ } (4-Py-COOH) ₄ X ₂ ] with isonicotinic acid 4-Py-COOH = L ² , where R1 = -OH: 200 mg of the octahedral chalcogen halide cluster complex of rhenium Cs _n [{Re ₆ Q ₈ } X ₆ ] (where X = Cl, Br or I; Q = S, n = 4; Q = Se, n = 3), k mg of isonicotinic acid in a ratio of 1:20 in moles ( where k is the mass of isonicotinic acid depending on the rhenium cluster complex used, k = 233, 208, 185, 209, 187 or 169 mg of isonicotinic acid for rhenium cluster complexes Cs ₄ [{Re ₆ S ₈ } Cl ₆ ], Cs ₄ [{Re ₆ S ₈ } Br ₆ ], Cs ₄ [{Re ₆ S ₈ } I ₆ ], Cs ₃ [{Re ₆ Se ₈ } Cl ₆ ], Cs ₃ [{Re ₆ Se ₈ } Br ₆ ] and whether Cs ₃ [{Re ₆ Se ₈ } I ₆ ], respectively) and 2 ml of dimethylformamide are loaded into glass ampoules, which are hermetically sealed (for example, sealed), heated to 100 ° C and kept at this temperature for 84 hours. The final product is isolated by adding ethyl alcohol to the reaction mixture. Product yields are ~ 70%.

The IR (infrared) spectra of the obtained compounds contain all vibration bands characteristic of the coordinated organic ligand. According to elemental analysis for Re ₆ S ₈ Cl ₂ C ₂₄ H ₂₀ N ₄ O ₈ theoretical mass content of elements (%): C 14.9; H 1.0; N, 2.9; experimentally found mass content of elements (%): C 14.8; H 1.0; N, 2.8. For Re ₆ S ₈ Br ₂ C ₂₄ H ₂₀ N ₄ O ₈ theoretical mass content of elements (%): C 14.2; H 1.0; N 2.8; experimentally found mass content of elements (%): C 14.4; H 0.9; N 2.7. For Re ₆ S ₈ I ₂ C ₂₄ H ₂₀ N ₄ O ₈ theoretical mass content of elements (%): C 13.6; H 1.0; N 2.6; experimentally found mass content of elements (%): C 13.8; H 0.9; N, 2.6. For Re ₆ Se ₈ Cl ₂ C ₂₄ H ₂₀ N ₄ O ₈ theoretical mass content of elements (%): C 12.5; H 0.9; N, 2.4; experimentally found mass content of elements (%): C 12.3; H 0.9; N, 2.4. For Re ₆ Se ₈ Br ₂ C ₂₄ H ₂₀ N ₄ O ₈ theoretical mass content of elements (%): C 12.0; H 0.8; N 2,3; experimentally found mass content of elements (%): C 11.8; H 0.9; N, 2.4. For Re ₆ Se ₈ I ₂ C ₂₄ H ₂₀ N ₄ O ₈ theoretical mass content of elements (%): C 11.6; H 0.8; N 2,3; experimentally found mass content of elements: C 11.6; H 0.9; N, 2.3.

Thus, cluster complexes of rhenium with the composition [{Re ₆ Q ₈ } (4-Py-COOH) ₄ X ₂ ] with isonicotinic acid 4-Py-COOH = L ² , where R1 = -OH, were obtained.

The syntheses of octahedral rhenium cluster complexes of the composition [{Re ₆ Q ₈ } (3-Py-COOH) ₄ X ₂ ] with nicotinic acid 3-Py-COOH = L ¹ , where R1 = -OH, are carried out similarly to the syntheses of the rhenium octahedral cluster complexes composition [{Re ₆ Q ₈ } (4-Py-COOH) ₄ X ₂ ] with isonicotinic acid 4-Py-COOH. Product yields are ~ 70%.

Synthesis details of octahedral cluster complexes of the composition [{Re ₆ Q ₈ } (4-Py-CONH ₂ ) ₄ X ₂ ] with isonicotinamide (an isonicotinic acid derivative with an amino group) 4-Py-CONH ₂ = L ² , where R1 = -NH ₂ : 150 mg of the rshenium octahedral chalcogen halide cluster complex Cs _n [{Re ₆ Q ₈ } X ₆ ] (where X = Cl, Br or I; Q = S, n = 4; Q = Se, n = 3) are loaded into glass ampoules and k mg of isonicotinamide in a ratio of 1:20 by moles (where k is the mass of isonicotinamide depending on the rhenium cluster complex used, k = 172, 153, 137, 155, 139 or 126 mg of isonicotinamide for rhenium cluster complexes Cs ₄ [{Re ₆ S ₈ } Cl ₆ ], C s ₄ [{Re ₆ S ₈ } Br ₆ ], Cs ₄ [{Re ₆ S ₈ } I ₆ ], Cs ₃ [{Re ₆ Se ₈ } Cl ₆ ], Cs ₃ [{Re ₆ Se ₈ } Br ₆ ] or Cs ₃ [{Re ₆ Se ₈ } I ₆ ] respectively) and 1 ml of dimethylformamide. The ampoules are hermetically sealed (for example, sealed), heated to 100 ° C and kept at this temperature for 84 hours. The final product is isolated by adding diethyl ether to the reaction mixture and washed with methanol. Product yields are ~ 55%.

The IR spectra of the obtained compounds contain all vibrational bands characteristic of the coordinated organic ligand. According to elemental analysis for Re ₆ S ₈ Cl ₂ C ₂₄ H ₂₄ N ₈ O ₄ experimentally found mass content of elements (%): C 14.9; H 1.3; N, 5.8; theoretical mass content of elements (%): C 15.0; H 1.2; N, 5.9. For Re ₆ S ₈ Br ₂ C ₂₄ H ₂₄ N ₈ O _{4 the} experimentally found mass content of elements (%): C 14.3; H 1.2; N 5.5; theoretical mass content of elements (%): C 14.4; H 1.1; N 5.5. For Re ₆ S ₈ I ₂ C ₂₄ H ₂₄ N ₈ O _{4 the} experimentally found mass content of elements (%): C 13.6; H 1.1; N, 5.3; theoretical mass content of elements (%): C 13.5; H 1.2; N, 5.3. For Re ₆ S ₈ Cl ₂ C ₂₄ H ₂₄ N ₈ O _{4 the} experimentally found mass content of elements (%): C 12.5; H 1.1; N, 4.9; theoretical mass content of elements (%): C 12.4; H 1.2; N 4.7. For Re ₆ Se ₈ Br ₂ C ₂₄ H ₂₄ N ₈ O _{4 the} experimentally found mass content of elements (%): C 12.0; H 1.0; N 4.7; theoretical mass content of elements (%): C 11.9; H 1.1; N, 4.5. For Re ₆ Se ₈ I ₂ C ₂₄ H ₂₄ N ₈ O _{4 the} experimentally found mass content of elements (%): C 11.6; H 1.0; N 4,5; theoretical mass content of elements (%): C 11.6; H 1.1; N, 4.5.

Thus, cluster complexes of rhenium with the composition [{Re ₆ Q ₈ } (4-Py-CONH ₂ ) ₄ X ₂ ] with isonicotinamide (an isonicotinic acid derivative with an amino group) 4-Py-CONH ₂ = L ² , where R1 = -NH ₂ .

The syntheses of octahedral cluster complexes of rhenium with the composition [{Re ₆ Q ₈ } (3-Py-CONH ₂ ) ₄ X ₂ ] with nicotinamide 3-Py-CONH ₂ = L ¹ , where R1 = -NH ₂ , are carried out similarly to the above syntheses of octahedral cluster rhenium complexes of the composition [{Re ₆ Q ₈ } (4-Py-CONH ₂ ) ₄ X ₂ ] with isonicotinamide 4-Py-CONH ₂ . Product yields are ~ 80%

Details of the syntheses of octahedral rhenium cluster complexes of the composition [{Re ₆ Q ₈ } (4-Py-C (O) NHC (CH ₂ OH) ₃ ) ₄ X ₂ ] with the isonicotinic acid derivative with 2-hydroxymethyl-propane-1,3- diol-2-amino-group 4-Py-C (O) NHC (CH ₂ OH) ₃ = L ² , where R1 = -NHC (CH ₂ OH) ₃ : 150 mg of the octahedral chalcogen halide cluster complex of rhenium Cs _n [{Re ₆ Q ₈ } X ₆ ] (X = Cl, Br or I; Q = S, n = 4; Q = Se, n = 3) and k mg 4-Py-C (O) NHC (CH ₂ OH) ₃ in a ratio of 1:20 by moles (where k is the mass of 4-Py-C (O) NHC (CH ₂ OH) ₃ depending on the cluster complex of rhenium used, k = 389, 337, 296, 326, 289 or 258 mg 4-Py-C (O) NHC (CH ₂ OH) ₃ for rhenium cluster complexes Cs ₄ [{Re ₆ S ₈ } Cl ₆ ], Cs ₄ [{Re ₆ S ₈ } Br ₆ ], Cs ₄ [{Re ₆ S ₈ } I ₆ ], Cs ₃ [{Re ₆ Se ₈ } Cl ₆ ], Cs ₃ [{Re ₆ Se ₈ } Br ₆ ] or Cs ₃ [{Re ₆ Se ₈ } I ₆ ], respectively) and 1 ml of dimethylformamide are loaded into glass ampoules, which are hermetically sealed (for example, sealed), heated to 100 ° C and kept at this temperature for 84 hours. The final product is isolated by adding diethyl ether to the reaction mixture and washed with methanol. Product yields are ~ 60%.

Compounds are characterized by ¹ H NMR spectroscopy. IR spectra contain all vibrational bands characteristic of a coordinated organic ligand. According to elemental analysis for Re ₆ S ₈ Cl ₂ C ₄₀ H ₆₄ N ₈ O ₁₆ experimentally found mass content of elements (%): C 20.4; H 2.7; N 4.8; theoretical mass content of elements (%): C 20.3; H 2.6; N 4.7. For Re ₆ S ₈ Br ₂ C ₄₀ H ₆₄ N ₈ O _{16 the} experimentally found mass content of elements (%): C 19.6; H 2.6; N, 4.6; theoretical mass content of elements (%): C 19.3; H 2.5; N, 4.4. For Re ₆ S ₈ I ₂ C ₄₀ H ₆₄ N ₈ O _{16 the} experimentally found mass content of elements (%): C 18.9; H 2.5; N, 4.4; theoretical mass content of elements (%): C 19.0; H 2.5; N, 4.5. For Re ₆ Se ₈ Cl ₂ C ₄₀ H ₆₄ N ₈ O _{16 the} experimentally found mass content of elements (%): C 17.6; H 2.4; N, 4.1; theoretical mass content of elements (%): C 17.4; H 2.4; N, 4.2. For Re ₆ Se ₈ Br ₂ C ₄₀ H ₆₄ N ₈ O _{16 the} experimentally found mass content of elements (%): C 17.0; H 2.3; N 4.0; theoretical mass content of elements (%): C 16.7; H 2.2; N, 3.9. For Re ₆ Se ₈ I ₂ C ₄₀ H ₆₄ N ₈ O _{16 the} experimentally found mass content of elements (%): C 16.5; H 2.2; N, 3.8; theoretical mass content of elements: C 16.4; H 2.3; N, 3.8.

Thus, rhenium cluster complexes of the composition [{Re ₆ Q ₈ } (4-Py-C (O) NHC (CH ₂ OH) ₃ ) ₄ X ₂ ] with the isonicotinic acid derivative with 2-hydroxymethyl-propan-1, 3-diol-2-amino-group 4-Py-C (O) NHC (CH ₂ OH) ₃ = L ² , where R1 = -NHC (CH ₂ OH) ₃ .

Similar to the synthesis of octahedral cluster complexes of rhenium with the composition [{Re ₆ Q ₈ } (4-Py-C (O) NHC (CH ₂ OH) ₃ ) ₄ X ₂ ] with the isonicotinic acid derivative with hydroxymethyl-propane-1,3- diol-2-amino-group 4-Py-C (O) NHC (CH ₂ OH) ₃ carry out:

- syntheses of octahedral cluster complexes of rhenium with the composition: [{Re ₆ Q ₈ } (3-Py-C (O) NHC (CH ₂ OH) ₃ ) ₄ X ₂ ] with a derivative of nicotinic acid with hydroxymethyl-propane-1,3-diol By the -2-amino group 3-Py-C (O) NHC (CH ₂ OH) ₃ = L ¹ , where R1 = -NHC (CH ₂ OH) ₃ , the product yields are ~ 60%;

- syntheses of [{Re ₆ Q ₈ } (4-Py-C (O) N (CH ₂ CH ₂ OH) ₂ ) ₄ X ₂ ] with an isonicotinic acid derivative with diethanolamino group 4-Py-C (O) N ( CH ₂ CH ₂ OH) ₂ = L ² , where R1 = -N (CH ₂ CH ₂ OH) ₂ , the product yields are ~ 55%;

- syntheses of [{Re ₆ Q ₈ } (3-Py-C (O) N (CH ₂ CH ₂ OH) ₂ ) ₄ X ₂ ] with a nicotinic acid derivative with diethanolamino group 3-Py-C (O) N ( CH ₂ CH ₂ OH) ₂ = L ¹ , where R1 = -N (CH ₂ CH ₂ OH) ₂ , the product yields are -50%;

- syntheses of [{Re ₆ Q ₈ } (4-Py-C (O) NHCH ₂ CH (OH) CH ₂ OH) ₄ X ₂ ] with an isonicotinic acid derivative with a propane-2,3-diol-1-amino group 4-Py-C (O) NHCH ₂ CH (OH) CH ₂ OH = L ² , where R1 = -NHCH ₂ CH (OH) CH ₂ OH, the product yields are ~ 70%;

- syntheses of [{Re ₆ Q ₈ } (3-Py-C (O) NHCH ₂ CH (OH) CH ₂ OH) ₄ X ₂ ] with a nicotinic acid derivative with a propane-2,3-diol-1-amino group 3-Py-C (O) NHCH ₂ CH (OH) CH ₂ OH = L ¹ , where R1 = -NHCH ₂ CH (OH) CH ₂ OH, the product yields are ~ 80%;

- syntheses [{Re ₆ Q ₈ } (4-Py-C (O) NHCH (CH ₂ OH) ₂ ) ₄ X ₂ ] with an isonicotinic acid derivative with a propane-1,3-diol-2-amino group 4- Py-C (O) NHCH (CH ₂ OH) ₂ = L ² , where R1 = -NHCH (CH ₂ OH) ₂ , the product yields are ~ 70%;

- synthesis of [{Re ₆ Q ₈ } (3-Py-C (O) NHCH (CH ₂ OH) ₂ ) ₄ X ₂ ] with a nicotinic acid derivative with propane-1,3-diol-2-amino-group 3- Py-C (O) NHCH (CH ₂ OH) ₂ = L ¹ , where R1 = -NHCH (CH ₂ OH) ₂ , the product yields are ~ 80%.

Synthesis Details of Octahedral Rhenium Cluster Complexes Composition [{Re ₆ Q ₈ } (4-Ru-С (O) ОСН ₂ СН (ОН) СН (ОН) СН (ОН) СН (ОН) СН ₂ ОН) ₆ ] X ₂ s a derivative of isonicotinic acid with hexane-2,3,4,5,6-pentaol-1-hydroxy-group 4-Ru-C (O) OCH ₂ CH (OH) CH (OH) CH (OH) CH (OH) CH ₂ OH = L ² , where R1 = —OCH ₂ CH (OH) CH (OH) CH (OH) CH (OH) CH ₂ OH: 150 mg of the rhenium chalcogen halide cluster complex Cs _n [{Re ₆ Q ₈ } X ₆ ] (X = Cl, Br or I; Q = S, n = 4; Q = Se, n = 3) and k mg 4-Ru-C (O) OCH ₂ CH (OH) CH (OH) CH (OH ) CH (OH) CH ₂ OH in a ratio of 1:20 by moles (where k is the mass of 4-Ru-C (O) OCH ₂ CH (OH) CH (OH) CH (OH) CH (OH) CH ₂ OH depending on used to the rhenium cluster complex, k = 203, 229, 256, 226, 252 or 279 mg of 4-Ru-C (O) OCH ₂ CH (OH) CH (OH) CH (OH) CH (OH) CH ₂ OH for cluster complexes rhenium Cs ₄ [{Re ₆ S ₈ } Cl ₆ ], Cs ₄ [{Re ₆ S ₈ } Br ₆ ], Cs ₄ [{Re ₆ S ₈ } I ₆ ], Cs ₃ [{Re ₆ Se ₈ } Cl ₆ ], Cs ₃ [{Re ₆ Se ₈ } Br ₆ ] or Cs ₃ [{Re ₆ Se ₈ } I ₆ ] respectively) and 1 ml of dimethylformamide are loaded into glass ampoules, which are hermetically sealed, heated to 100 ° C and maintained at this temperature for 84 hours. The final product is isolated by adding diethyl ether to the reaction mixture and washed with ethanol. Product yields are ~ 60%.

IR spectra contain all vibrational bands characteristic of a coordinated organic ligand. According to elemental analysis for Re ₆ S ₈ Cl ₂ C ₇₂ H ₁₀₂ N ₆ O _{42 the} experimentally found mass content of elements (%): C 27.3; H 3.2; N 2.7; theoretical mass content of elements (%): C 27.3; H 3.2; N, 2.9. For Re ₆ S ₈ Br ₂ C ₇₂ H ₁₀₂ N ₆ O _{42 the} experimentally found mass content of elements (%): C 26.6; H 3.2; N 2.6; theoretical mass content of elements (%): C 26.4; H 3.1; N, 2.4. For Re ₆ S ₈ I ₂ C ₇₂ H ₁₀₂ N ₆ O _{42 the} experimentally found mass content of elements (%): C 25.8; H 3.1; N 2.5; theoretical mass content of elements (%): C 25.7; H 3.2; N 2.5. For Re ₆ Se ₈ Cl ₂ C ₇₂ H ₁₀₂ N ₆ O _{42 the} experimentally found mass content of elements (%): C 24.4; H 2.9; N, 2.4; theoretical mass content of elements (%): C 24.4; H 3.0; N, 2.3. For Re ₆ Se ₈ Br ₂ C ₇₂ H ₁₀₂ N ₆ O _{42 the} experimentally found mass content of elements (%): C 23.8; H 2.8; N 2,3; theoretical mass content of elements (%): C 23.9; H 2.8; N, 2.4. For Re ₆ Se ₈ I ₂ C ₇₂ H ₁₀₂ N ₆ O _{42 the} experimentally found mass content of elements (%): C 23.2; H 2.8; N 2,3; theoretical mass content of elements (%): C 23.3; H 2.9; N, 2.4.

Thus, cluster complexes of rhenium with the composition [{Re ₆ Q ₈ } (4-Py-C (O) OCH ₂ CH (OH) CH (OH) CH (OH) CH (OH) CH ₂ OH) ₆ ] X2 with an isonicotinic acid derivative with hexane-2,3,4,5,6-pentaol-1-hydroxy-group 4-Ru-C (O) OCH ₂ CH (OH) CH (OH) CH (OH) CH (OH) CH ₂ OH = L ² , where R1 = —OCH ₂ CH (OH) CH (OH) CH (OH) CH (OH) CH ₂ OH.

Similar to the synthesis of octahedral cluster complexes of rhenium with the composition [{Re ₆ Q ₈ } (4-Py-C (O) OCH ₂ CH (OH) CH (OH) CH (OH) CH (OH) CH ₂ OH) ₆ ] X ₂ s a derivative of isonicotinic acid with hexane-2,3,4,5,6-pentaol-1-hydroxy-group 4-Ru-C (O) OCH ₂ CH (OH) CH (OH) CH (OH) CH (OH) CH ₂ OH carry out the synthesis of octahedral cluster complexes of rhenium composition:

- [{Re ₆ Q ₈ } (3-Py-C (O) OCH ₂ CH (OH) CH (OH) CH (OH) CH (OH) CH ₂ OH) ₆ ] X ₂ with a derivative of nicotinic acid with hexane 2,3,4,5,6-pentaol-1-hydroxy-group 4-Ru-C (O) OCH ₂ CH (OH) CH (OH) CH (OH) CH (OH) CH ₂ OH = L ¹ , where R1 = —OCH ₂ CH (OH) CH (OH) CH (OH) CH (OH) CH ₂ OH, the product yields are ~ 60%;

- [{Re ₆ Q ₈ } (4-Ru-C (O) OCH ₂ CH (OH) CH (OH) CH (OH) CH (OH) CH ₂ O [C ₃ N ₃ ] (OCH ₂ CH (OH ) CH (OH) CH (OH) CH (OH) CH ₂ OH) ₂ ) ₆ ] X ₂ with an isonicotinic acid derivative with 6- (4,6-bis- (hexane-2,3,4,5,6- pentaol-1-hydroxy) -1,3,5-triazine) -hexane-2,3,4,5, -pentaol-1-hydroxy-group 4-Ru-C (O) OCH ₂ CH (OH) CH ( OH) CH (OH) CH (OH) CH ₂ O [C ₃ N ₃ ] (OCH ₂ CH (OH) CH (OH) CH (OH) CH (OH) CH ₂ OH) ₂ = L ² , where R1 = -

OCH ₂ CH (OH) CH (OH) CH (OH) CH (OH) CH ₂ O [C ₃ N ₃ ] (OCH ₂ CH (OH) CH (OH) CH (OH) CH (OH) CH ₂ OH) ₂ , product yields are ~ 70%;

- [{Re ₆ Q ₈ } (3-Py-C (O) OCH ₂ CH (OH) CH (OH) CH (OH) CH (OH) CH ₂ O [C ₃ N ₃ ] (OCH ₂ CH (OH ) CH (OH) CH (OH) CH (OH) CH ₂ OH) ₂ ) ₆ ] X ₂ with a derivative of nicotinic acid with 6- (4,6-bis- (hexane-2,3,4,5,6- pentaol-1-hydroxy) -1,3,5-triazine) -hexane-2,3,4,5, -pentaol-1-hydroxy-3-Py-C (O) OCH ₂ CH (OH) CH ( OH) CH (OH) CH (OH) CH ₂ O [C ₃ N ₃ ] (OCH ₂ CH (OH) CH (OH) CH (OH) CH (OH) CH ₂ OH) ₂ = L ² , where R1 = -OCH ₂ CH (OH) CH (OH) CH (OH) CH (OH) CH ₂ O [C ₃ N ₃ ] (OCH ₂ CH (OH) CH (OH) CH (OH) CH (OH) CH ₂ OH ) ₂ , the product yields are ~ 50%.

Example 2, in which L ¹ and L ² are Schiff bases derived from 4-pyridinaldehyde or 3-pyridinaldehyde containing polyalcohol groups R2:

or

In this case, R2 means:

Tris- (hydroxymethyl) methyl group (-C (CH ₂ OH) ₃ ):

or 2,3-dihydroxypropyl group (-CH ₂ CH (OH) CH ₂ OH):

or bis- (hydroxymethyl) methyl group (-CH (CH ₂ OH) ₂ ):

The proposed complexes can be obtained as follows.

Details of the syntheses of octahedral rhenium cluster complexes of the composition [{Re ₆ Q ₈ } (4-Py-CH = MS (CH ₂ OH) ₃ ) ₆ ] X ₂ with a Schiff base derivative derived from 4-pyridinaldehyde with tris- (hydroxymethyl) methyl group 4-Py-CH = NC (CH ₂ OH) ₃ = L ¹ , where R2 = -С (CH ₂ OH) ₃ : 150 mg of the octahedral chalcogen halide cluster complex of rhenium Cs _n [{Re ₆ Q ₈ } X ₆ ] (X = Cl, Br or I; Q = S, n = 4; Q = Se, n = 3) and k mg 4-Py-CH = NC (CH ₂ OH) ₃ in a ratio of 1:20 in moles (where k is the mass of 4-Py-CH = NC (CH ₂ OH) ₃ depending on the rhenium cluster complex used, k = 362, 314, 275, 303, 269 or 240 mg of 4-Py-CH = NC (CH ₂ OH ) ₃ for rhenium cluster complexes Cs ₄ [{Re ₆ S ₈ } Cl ₆ ], Cs ₄ [{Re ₆ S ₈ } Br ₆ ], Cs ₄ [{Re ₆ S ₈ } I ₆ ], Cs ₃ [{Re ₆ Se ₈ } Cl ₆ ], Cs ₃ [ {Re ₆ Se ₈ } Br ₆ ] or Cs ₃ [{Re ₆ Se ₈ } I ₆ ] respectively) and 1 ml of dimethylformamide are loaded into glass ampoules, which are hermetically sealed, heated to 100 ° C and kept at this temperature for 84 hours. The final product is isolated by adding diethyl ether to the reaction mixture and washed with methanol. Product yields are ~ 90%.

Compounds are characterized by ¹ H NMR spectroscopy. IR spectra contain all vibrational bands characteristic of a coordinated organic ligand. According to elemental analysis for Re ₆ S ₈ Cl ₂ C ₆₀ H ₈₄ N ₁₂ O ₁₈ experimentally found mass content of elements (%): C 26.6; H 3.1; N, 6.2; theoretical mass content of elements (%): C 26.6; H 3.1; N, 6.3. For Re ₆ S ₈ Br ₂ C ₆₀ H ₈₄ N ₁₂ O ₁₈ experimentally found mass content of elements (%): C 25.8; H 3.0; N 6.0; theoretical mass content of elements (%): C 25.6; H 3.0; N, 6.0. For Re ₆ S ₈ I ₂ C ₆₀ H ₈₄ N ₁₂ O ₁₈ experimentally found mass content of elements (%): C 24.9; H 2.9; N, 5.8; theoretical mass content of elements (%): C 24.9; H 2.8; N, 5.7. For Re ₆ Se ₈ Cl ₂ C ₆₀ H ₈₄ N ₁₂ O ₁₈ experimentally found mass content of elements (%): C 23.4; H 2.8; N 5.5; theoretical mass content of elements (%): C 23.3; H 2.7; N, 5.3. For Re ₆ Se ₈ Br ₂ C ₆₀ H ₈₄ N ₁₂ O ₁₈ experimentally found mass content of elements (%): C 22.7; H 2.7; N, 5.3; theoretical mass content of elements (%): C 22.5; H 2.7; N, 5.3. For Re ₆ Se ₈ I ₂ C ₆₀ H ₈₄ N ₁₂ O ₁₈ experimentally found mass content of elements (%): C 22.1; H 2.6; N, 5.2; theoretical mass content of elements (%): C 22.1; H 2.7; N, 5.2.

Thus, cluster complexes of rhenium with the composition [{Re ₆ Q8} (4-Py-CH = NC (CH ₂ OH) ₃ ) ₆ ] X ₂ with a Schiff base derivative derived from 4-pyridinaldehyde with tris- (hydroxymethyl) were obtained ) methyl group 4-Py-CH = NC (CH ₂ OH) ₃ = L ¹ , where R2 = -C (CH ₂ OH) ₃ .

Similar to the syntheses of octahedral rhenium cluster complexes of the composition [{Re ₆ Q ₈ } (4-Py-CH = NC (CH ₂ OH) ₃ ) ₆ ] X ₂ with a Schiff base derivative derived from 4-pyridinaldehyde with tris- (hydroxymethyl) methyl group 4-Py-CH = NC (CH ₂ OH) ₃ carry out the synthesis of octahedral cluster complexes of rhenium composition:

- [{Re ₆ Q ₈ } (3-Py-CH = NC (CH ₂ OH) ₃ ) ₆ ] X ₂ with a Schiff base derivative derived from 3-pyridinaldehyde with the tris (hydroxymethyl) methyl group 3-Ru- CH = NC (CH ₂ OH) ₃ = L ² , where R2 = -C (CH ₂ OH) ₃ , the product yields are ~ 50%;

- [{Re ₆ Q ₈ } (4-Py-CH = NCH ₂ CH (OH) CH ₂ OH) ₆ ] X ₂ with a Schiff base derivative derived from 4-pyridinaldehyde with a 2,3-dihydroxypropyl group 4-Py -CH = NCH ₂ CH (OH) CH ₂ OH = L ¹ , where R2 = -CH ₂ CH (OH) CH ₂ OH, the product yields are ~ 70%;

- [{Re ₆ Q ₈ } (3-Py-CH = NCH ₂ CH (OH) CH ₂ OH) ₆ ] X ₂ with a Schiff base derivative derived from 3-pyridinaldehyde with a 2,3-dihydroxypropyl group of 3-Py -CH = NCH ₂ CH (OH) CH ₂ OH = L ² , where R2 = -CH ₂ CH (OH) CH ₂ OH, the product yields are ~ 80%;

- [{Re ₆ Q ₈ } (4-Py-CH = NCH (CH ₂ OH) ₂ ) ₆ ] X ₂ with a Schiff base derivative derived from 4-pyridinaldehyde with a bis (hydroxymethyl) methyl group 4-Ru- CH = NCH (CH ₂ OH) ₂ = L ¹ , where R2 = —CH (CH ₂ OH) ₂ , the product yields are ~ 80%;

- [{Re ₆ Q ₈ } (3-Py-CH = NCH (CH ₂ OH) ₂ ) ₆ ] X ₂ with a Schiff base derivative derived from 3-pyridinaldehyde with a bis (hydroxymethyl) methyl group 3-Ru- CH = NCH (CH ₂ OH) ₂ = L ² , where R2 = —CH (CH ₂ OH) ₂ , the product yields are ~ 75%.

Option 2. The problem is solved by creating a radiopaque substance described by the formula [{Re ₆ Q ₈ } L ^l _n L ² _m Y _6-nm ] ^q ,

containing an octahedral cluster core {Re ₆ Q ₈ }, where: Q - S or Se;

n is 0, 1, 2, 3, 4 or 5; m is 0, 1, 2, 3, 4 or 5; n + m = 0, 1, 2, 3, 4 or 5; q = 10-, 8-, 6-, 4-, 2- or 0; Y is a doubly charged anionic ligand of organic or inorganic nature and can be selected from the series:

SO ₃ ^2- , S ₂ O ₃ ^2- , SeSO ₃ ^2- , SeO ₃ ^2- , HPO ₄ ^2- , HPO ₃ ^2- , C ₂ O ₄ ^2- , ^- OOC- (M) _n -COO ^- , where n is 0-6, and M is the limit or unsaturated aliphatic or aromatic residue, including containing fluorine.

L ¹ and L ² are pyridine-containing ligands that are linked to the cluster core via a Re-N bond, and are selected from a number of nicotinic or isonicotinic acid derivatives containing, in the composition of the R1 group: hydroxy or amino groups; or selected from a number of derivatives of 4-pyridinaldehyde or 3-pyridinaldehyde containing in the composition of group R2: tris- (hydroxymethyl) methyl or 2,3-dihydroxypropyl or bis- (hydroxymethyl) methyl groups.

Example 3, in which L ¹ and L ² are derivatives of nicotinic or isonicotinic acids containing R1 groups:

или

or

In this case, R1 means:

hydroxy groups

OH

or amino groups

NH ₂

The proposed complex compounds can be obtained as follows.

Details of the synthesis of octahedral cluster complexes of the composition Na ₂ [{Re ₆ Q ₈ } (4-Py-COOH) ₄ (SO ₃ ) ₂ ] with isonicotinic acid 4-Py-COOH = L ² , where R1 = -OH: 100 mg of octahedral rhenium hexasulfite cluster complex Na ₁₀ [{Re ₆ Q ₈ } (SO ₃ ) ₆ ] and k mg of isonicotinic acid in a ratio of 1:20 mol (where k is the mass of isonicotinic acid depending on the used rhenium cluster complex, k = 118 or 100 mg of isonicotinic acid for rhenium cluster complexes Na ₁₀ [{Re ₆ S ₈ } (SO ₃ ) ₆ ] or Na ₁₀ [{Re ₆ Se ₈ } (SO ₃ ) 9 ₆ ], respectively) and 3 ml of water are loaded into glass ampoules e is sealed and heated to 100 ° C and kept at this temperature for 24 hours. The final solution was filtered and evaporated to dryness. Product yields are ~ 70%.

Compounds are characterized by ¹ H NMR spectroscopy. IR spectra contain all vibrational bands characteristic of a coordinated organic ligand. According to the data of elemental analysis for Na ₂ Re ₆ S ₁₀ C ₃₆ H ₂₀ N ₄ O ₁₄ experimentally found mass content of elements (%): C 19.5; H 0.9; N 2.5; theoretical mass content of elements (%): C 19.6; H 1.1; N, 2.4. For Na ₂ Re ₆ Se ₈ S ₂ C ₃₆ H ₂₀ N ₄ O _{14 the} experimentally found mass content of elements (%): C 16.1; H 0.8; N, 2.1; theoretical mass content of elements (%): C 16.2; H 0.9; N, 2.2.

Thus, cluster complexes of rhenium with the composition Na ₂ [{Re ₆ Q ₈ } (4-Py-COOH) ₄ (SO ₃ ) ₂ ] with isonicotinic acid 4-Py-COOH = L ² , where R1 = -OH, were obtained.

The synthesis of octahedral rhenium cluster complexes of the composition Na ₂ [{Re ₆ Q ₈ } (3-Py-COOH) ₄ (SO ₃ ) ₂ ] with nicotinic acid 3-Py-COOH = L ¹ , where R1 = -OH, is carried out similarly to the above the synthesis of octahedral cluster complexes of rhenium of the composition Na ₂ [{Re ₆ Q ₈ } (4-Py-COOH) ₄ (SO ₃ ) ₂ ] with isonicotinic acid 4-Py-COOH. Product yields are ~ 85%.

Details of the syntheses of octahedral rhenium cluster complexes of the composition Na ₂ [{Re ₆ Q ₈ } (4-Py-CONH ₂ ) ₄ (SO ₃ ) ₂ ] with isonicotinamide (an isonicotinic acid derivative with an amino group) 4-Py-CONH ₂ = L ² , where R1 = -NH ₂ : 100 mg of the octahedral hexasulfite cluster complex of rhenium Na ₁₀ [{Re ₆ Q ₈ } (SO ₃ ) ₆ ] and k mg of isonicotinamide in a ratio of 1:20 mol (where k is the mass of isonicotinamide in depending on the rhenium cluster complex used, k = 117 or 138 mg of isonicotinamide for the rhenium cluster complexes Na ₁₀ [{Re ₆ S ₈ } (SO ₃ ) ₆ ] or Na ₁₀ [{Re ₆ Se ₈ } (SO ₃ ) ₆ ], respectively ) and 2 ml of dimethylfo rmamide is loaded into glass ampoules, which are hermetically sealed, heated to 100 ° C and maintained at this temperature for 24 hours. The final solutions are filtered off, and the reaction product is isolated by adding diethyl ether to the solution. Product yields are ~ 65%.

Compounds are characterized by ¹ H NMR spectroscopy. IR spectra contain all vibrational bands characteristic of a coordinated organic ligand. According to the data of elemental analysis for Na ₂ Re ₆ S ₁₀ C ₂₄ H ₂₄ N ₈ O ₁₀ experimentally found mass content of elements (%): C 13.9; H 1.2; N, 5.4; theoretical mass content of elements (%): C 13.9; H 1.2; N, 5.4. For Na ₂ Re ₆ Se ₈ S ₂ C ₂₄ H ₂₄ N ₈ O _{10 the} experimentally found mass content of elements (%): C 11.8; H 1.0; N, 4.6; theoretical mass content of elements (%): C 11.8; H 1.0; N, 4.6.

Thus, cluster complexes of rhenium with the composition Na ₂ [{Re ₆ Q ₈ } (4-Py-CONH ₂ ) ₄ (SO ₃ ) ₂ ] with isonicotinamide (a derivative of isonicotinic acid with an amino group) 4-Py-CONH ₂ were obtained = L ² , where R1 = -NH ₂ .

The synthesis of octahedral cluster complexes of rhenium with the composition Na ₂ [{Re ₆ Q ₈ } (3-Py-CONH ₂ ) ₄ (SO ₃ ) ₂ ] with nicotinamide 3-Py-CONH ₂ = L ¹ , where R1 = -NH ₂ , is carried out similar to the synthesis of octahedral rhenium cluster complexes of the composition Na ₂ [{Re ₆ Q ₈ } (4-Py-CONH ₂ ) ₄ (SO ₃ ) ₂ ] with isonicotinamide 4-Py-CONH ₂ . Product yields are ~ 65%.

Example 4, in which L ¹ and L ² are derivatives of 4-pyridinaldehyde or 3-pyridinaldehyde containing polyalcohol groups R2:

or

In this case, R2 means:

Tris- (hydroxymethyl) methyl group (-C (CH ₂ OH) ₃ ):

or 2,3-dihydroxypropyl group (-CH ₂ CH (OH) CH ₂ OH):

or bis- (hydroxymethyl) methyl group (-CH (CH ₂ OH) ₂ ):

The proposed complex compounds can be obtained as follows.

Synthesis Details of Octahedral Rhenium Cluster Complexes of the Composition Na ₂ [{Re ₆ Q ₈ } (4-Py-CH = NC (CH ₂ OH) ₃ ) ₄ (SO ₃ ) ₂ ] with a Schiff Base Derivative Derived from 4-Pyridinaldehyde, s tris- (hydroxymethyl) methyl group 4-Py-CH = NC (CH ₂ OH) ₃ = L ¹ , where R2 = -С (CH ₂ OH) ₃ : 150 mg of the octahedral hexasulfite cluster complex of rhenium Na ₁₀ [{Re ₆ Q ₈ } (SO ₃ ) ₆ ] (Q = S or Se) and k mg 4-Py-CH = NC (CH ₂ OH) ₃ in a ratio of 1:20 per mole (where k is the mass of 4-Py-CH = NC (CH ₂ OH) ₃ depending on the used rhenium cluster complex, k = 302 or 256 mg of 4-Py-CH = NC (CH ₂ OH) ₃ for rhenium cluster complexes Na ₁₀ [{Re ₆ S ₈ } (SO ₃ ) _6] and ₁₀ and Na [{Re ₆ Se _8} (SO _{3) 6],} respectively) and 1 ml of dimethylformamide was charged into a glass ampoule, which was sealed and heated to 100 ° C and kept at this temperature for 84 hours. The final solutions are filtered off, the reaction products are isolated by adding diethyl ether to the solutions and washed with methanol. Product yields are ~ 50%.

Compounds are characterized by ¹ H NMR spectroscopy. IR spectra contain all vibrational bands characteristic of a coordinated organic ligand. According to the data of elemental analysis for Na ₂ Re ₆ S ₁₀ SC ₄₀ H ₅₆ N ₈ O ₁₈ experimentally found mass content of elements (%): C 19.6; H 2.3; N, 4.6; theoretical mass content of elements (%): C 19.7; H 2.3; N, 4.5. For Na ₂ Re ₆ Se ₈ S ₂ C ₄₀ H ₅₆ N ₈ O ₁₈ experimentally found mass content of elements (%): C 17.2; H 2.0; N 4.0; theoretical mass content of elements (%): C 17.3; H 2.1; N, 4.0.

Thus, cluster complexes of rhenium of the composition Na ₂ [{Re ₆ Q ₈ } (4-Py-CH = NC (CH ₂ OH) ₃ ) ₄ (SO ₃ ) ₂ ] with a Schiff base derivative derived from 4-pyridinaldehyde were obtained , with tris- (hydroxymethyl) methyl group 4-Py-CH = NC (CH ₂ OH) ₃ = L ¹ , where R2 = -C (CH ₂ OH) ₃ .

Similar to syntheses of octahedral rhenium cluster complexes of the composition Na ₂ [{Re ₆ Q ₈ } (4-Py-CH = NC (CH ₂ OH) ₃ ) ₄ (SO ₃ ) ₂ ] with a Schiff base derivative derived from 4-pyridinaldehyde, with Tris (hydroxymethyl) methyl group 4-Py-CH = NC (CH ₂ OH) ₃ synthesize octahedral rhenium cluster complexes of the composition:

- Na ₂ [{Re ₆ Q ₈ } (3-Py-CH = NC (CH ₂ OH) ₃ ) ₄ (SO ₃ ) ₂ ] with a Schiff base derivative derived from 3-pyridinaldehyde with tris- (hydroxymethyl) methyl group 3-Py-CH = NC (CH ₂ OH) ₃ = L ² , where R2 = -C (CH ₂ OH) ₃ , the product yields are ~ 65%;

- Na ₂ [{Re ₆ Q ₈ } (4-Py-CH = NCH ₂ CH (OH) CH ₂ OH) ₄ (SO ₃ ) ₂ ] with a Schiff base derivative derived from 4-pyridinaldehyde, with 2,3- dihydroxypropyl group 4-Py-CH = NCH ₂ CH (OH) CH ₂ OH = L ¹ , where R2 = -CH ₂ CH (OH) CH ₂ OH, the product yields are ~ 60%;

-Na ₂ [{Re ₆ Q ₈ } (3-Py-CH = NCH ₂ CH (OH) CH ₂ OH) ₄ (SO ₃ ) ₂ ] with a Schiff base derivative derived from 3-pyridinaldehyde, with 2,3- dihydroxypropyl group of 3-Py-CH = NCH ₂ CH (OH) CH ₂ OH = L ² , where R2 = -CH ₂ CH (OH) CH ₂ OH, the product yield is ~ 70%;

- Na ₂ [{Re ₆ Q ₈ } (4-Py-CH = NCH (CH ₂ OH) ₂ ) ₄ (SO ₃ ) ₂ ] with a Schiff base derivative derived from 4-pyridinaldehyde, with bis (hydroxymethyl) methyl the group 4-Py-CH = NCH (CH ₂ OH) ₂ = L ¹ , where R2 = -CH (CH ₂ OH) ₂ , the product yields are ~ 50%;

- Na ₂ [{Re ₆ Q ₈ } (3-Py-CH = NCH (CH ₂ OH) ₂ ) ₄ (SO ₃ ) ₂ ] with a Schiff base derivative derived from 3-pyridinaldehyde, with bis (hydroxymethyl) methyl group 3-Py-CH = NCH (CH ₂ OH) ₂ = L ² , where R2 = -CH (CH ₂ OH) ₂ , the product yields are ~ 55%.

The main method for the synthesis of radiopaque substances based on octahedral cluster complexes of rhenium is solvothermal synthesis under anhydrous conditions. The general chemical procedure is the interaction of inorganic chalcogenide cluster complexes of rhenium with pre-selected highly hydrophilic organic ligands L ¹ and / or L ² (polyhydroxyl derivatives of pyridine) in high-boiling aprotic polar solvents such as N, N-dimethylformamide, N, N-diethylformamide, , N-dimethylacetamide, N, N-diethylacetamide, dimethyl sulfoxide, N-methylpyrrolidone, 1,2-ethylene carbonate or 1,2-propylene carbonate.

Inorganic chalcogenide cluster complexes of rhenium can be either homoleptic or heteroleptic compounds of the type Me _x [{Re ₆ Q ₈ } X ₆ ] or Me _y [{Re ₆ Q ₈ } Y ₆ ], Me = alkali metal cations, or ammonium, or primary, or secondary, or tertiary, or Quaternary ammonium bases, proton or hydroxonium;

x = 3 or 4;

y = 10;

Q = S or Se;

X = F ^- , Cl ^- , Br ^- , I ^- , CN ^- , SCN ^- , SeCN ^- , OH ^- , NO ^- , NO ₂ ^- , NO ₃ ^- SH ^- , CF ₃ ^- , H ₂ PO ₄ ^- , H ₂ PO ₃ ^- , H ₂ PO ₂ ^- , HRCOO ^- or RSO ₃ ^- ; for example: Cs ₄ [{Re ₆ S ₈ } Br ₆ ], Cs ₃ [{Re ₆ Se ₈ } Br ₆ ], Na ₄ [{Re ₆ Se ₈ } (OH) ₆ ], Cs ₄ [{Re ₆ S ₈ } (OOCCH ₃ ) ₆ ] Na ₄ [{Re ₆ Se ₈ } (OH) ₂ (CN) ₄ ] or Na ₄ [{Re ₆ S ₈ } (OH) ₄ (CN) ₂ ];

Y = SO ₃ ^2- , S ₂ O ₃ ^2- , SeSO ₃ ^2- , SeO ₃ ^2- , HPO ₄ ^2- , HPO ₃ ^2- , C ₂ O ₄ ^2- , ^- OOS- (M) _n -COO ^- , where n is 0-6, and M is the limit or unsaturated aliphatic or aromatic residue, including containing fluorine, R is the limit or unsaturated aliphatic or aromatic residue, including containing fluorine, consisting of: -H, -CH ₃ , -CH ₂ CH ₃ , -CH ₂ CH ₂ CH ₃ , -CH (CH ₃ ) ₂ , -CH ₂ CH ₂ CH ₂ CH ₃ , -CH ₂ CH (CH ₃ ) ₂ , -CH (CH ₃ ) CH ₂ CH ₃ , -C (CH ₃ ) ₃ , -C ₆ H ₅ , -C ₆ H ₄ CH ₃ , -C ₅ H ₄ N, -CF ₃ , -CF ₂ CF ₃ , -CF ₂ CF ₂ CF ₃ , -CF (CF ₃ ) ₂ , -CF ₂ CF ₂ CF ₂ CF ₃ , -CF ₂ CF (CF ₃ ) ₂ , -CF (CF ₃ ) CF ₂ CF ₃ , -C (CF ₃ ) ₃ , - C ₆ F ₅ ; for example: K ₁₀ [{Re ₆ S ₈ } (SO ₃ ) ₆ ], Na ₁₀ [{Re ₆ S ₈ } (S ₂ O ₃ ) ₆ ], Na ₁₀ [{Re ₆ Se ₈ } (SeO ₃ ) ₆ ] or K ₄ H ₆ [{Re ₆ S ₈ } (OOC (CH ₂ ) ₄ COO) ₆ ].

Highly hydrophilic organic ligands L ¹ and / or L ² are synthetic derivatives of pyridine (nicotinic or isonicotinic acids, 4-pyridinaldehyde or 3-pyridinaldehyde) containing: hydroxy, amino, diethanolamino, propane-2,3-diol -1-amino, propane-1,3-diol-2-amino, 2-hydroxymethyl-propane-1,3-diol-2-amino, hexane-2,3,4,5,6-pentaol- 1-hydroxy- or 6- (4,6-bis- (hexane-2,3,4,5,6-pentaol-1-hydroxy) -1,3,5-triazine) -hexane-2,3,4 , 5, pentaol-1-hydroxy groups.

The proposed ligands can be obtained as follows.

Details of the synthesis of organic ligands based on isonicotinic acid with diethanolamino group 4-Py-C (O) N (CH ₂ CH ₂ OH) ₂ :

1.246 g of isonicotinic acid chloride is dissolved in 10 ml of tetrahydrofuran and 2.6 ml of tripropylamine is slowly added dropwise, then 0.8 g of diethanolamine is added and left to mix for one day. Then tetrahydrofuran was evaporated, the residue was washed with acetonitrile, the resulting oil was dissolved in ethanol, and filtered. Then the solution was evaporated, 4-Py-CON (CH ₂ CH ₂ OH) _{2 was} isolated from the obtained residue on a chromatographic column. Yield: 370 mg (25%).

Observed bands in the IR spectrum: υ _CONHR = 1630 cm ^-1 , υ _{CH, NH} = 3330 cm ^-1 (wide). According to elemental analysis for C ₁₀ H ₁₄ N ₂ O ₃ experimentally found mass content of elements (%): C 57.1; H 6.7; N 13.3; theoretical mass content of elements (%): C 57.3; H 6.3; N 13.2. NMR (500 MHz, DMSO-d ₆ , ppm): 3.237 (t, J = 6 Hz, 2H, NCH ₂ ), 3.426 (t, J = 6 Hz, 2H, NCH ₂ ), 3.508 (d, J = 6 Hz, 2H, CH ₂ OH), 3.605 (d, J = 6 Hz, 2H, CH ₂ OH), 4.77 (broad, 2H, OH), 7.357 (d, J = 5.5 Hz, 2H, CH _py ), 8.617 (d, J = 5.5 Hz, 2H, NCH _py ).

The synthesis of an organic ligand based on nicotinic acid with a diethanolamine group 3-Py-C (O) N (CH ₂ CH ₂ OH) _{2 is} carried out similarly to the synthesis of an organic ligand based on isonicotinic acid with a diethanolamine group 4-Py-C (O) N (CH ₂ CH ₂ OH) ₂ .

Synthesis of an isonicotinic acid-based organic ligand with hydroxymethyl-propane-1,3-diol-2-amino group 4-Ru-C (O) NHC (CH ₂ OH) ₃ :

360 mg of isonicotinic acid chloride is mixed with 2.42 g of tris- (hydroxymethyl) aminomethane in 7 ml of dimethylformamide. The reaction mixture in a closed container is kept in an oven at 100 ° C for 84 hours. Upon cooling, an excess of tris- (hydroxymethyl) aminomethane is precipitated. The precipitate is separated from the solution, the solution is concentrated, then a small amount of silicon dioxide is added and filtered through a layer of silica gel with chloroform and alcohol in a ratio of 10: 1. Then a mixture of chloroform and alcohol is evaporated and the crystals of the product are dried. Yield: 330 mg (73%). A single crystal suitable for X-ray diffraction was obtained by recrystallization from a mixture of ethyl acetate and alcohol.

The observed bands in the IR spectrum: υ _CONHR = 1640 cm ^-1 , υ _{CH, NH} = 3220 cm ^-1 (wide). NMR (500 MHz, DMSO-d ₆ , ppm): 3.421 (d, J = 5.5 Hz, 2H, CH ₂ OH), 3.516 (d, J = 6 Hz, 4H, CH ₂ OH), 3.683 (d, J = 5.5 Hz, 2H, CH ₂ OH), 4.634 (t, J = 5.5 Hz, 1H, CH _a ), 4.688 (t, J = 6 Hz, 2H, CH ₂ ), 4.704 (t, J = 5.5 Hz, 1H, CH _e ), 7.453 (m, pyridyl fragment), 7.676 (m, 2H, pyridyl fragment), 7.916 (m, pyridyl fragment), 8.139 (m, pyridyl fragment) 8.685 (m, 2H, pyridyl moiety). According to elemental analysis for C ₁₀ H ₁₈ N ₂ O ₆ experimentally found mass content of elements (%): C 45.8; H 6.9; N, 10.7; theoretical mass content of elements (%): C 46.2; H 7.0; N, 10.8.

The synthesis of the nicotinic acid-based organic ligand with hydroxymethyl-propane-1,3-diol-2-amino-group 3-Py-C (O) NHC (CH ₂ OH) _{3 is} carried out similarly to the synthesis of the isonicotinic acid-based organic ligand with hydroxymethyl- propane-1,3-diol-2-amino-group 4-Py-C (O) NHC (CH ₂ OH) ₃ .

Details of the synthesis of an organic ligand based on isonicotinic acid with hexane-2,3,4,5,6-pentaol-1-hydroxy-group 4-Ru-C (O) OCH ₂ CH (OH) CH (OH) CH ( OH) CH (OH) CH ₂ OH: 4.55 g of sorbitol is dissolved by heating to 140 ° C. in 25 ml of dimethylformamide. The mixture was cooled to 120 ° C. and 1.43 g of tripropylamine was added. The mixture was cooled to 100 ° C and a solution of 0.89 g of isonicotinic acid chloride in 5 ml of dimethylformamide was added. It is kept at 100 ° C for one hour, then the solvent is evaporated. The remaining solid is treated with acetone and ethanol and sorbitol is filtered off. Ethanol is evaporated and the reaction mixture is treated with ethyl acetate. Yield: 0.37 g (26%). According to elemental analysis for C ₁₂ H ₁₇ NO ₇ experimentally found mass content of elements (%): C 50.2; H 6.0; N, 4.9; theoretical mass content of elements (%): C 49.8; H 6.0; N, 4.8.

Synthesis of nicotinic acid-based organic ligand with hexane-2,3,4,5,6-pentaol-1-hydroxy-group 3-Ru-C (O) OCH ₂ CH (OH) CH (OH) CH (OH) CH (OH) CH ₂ OH is carried out analogously to the synthesis of an isonicotinic acid-based organic ligand with hexane-2,3,4,5,6-pentaol-1-hydroxy-group 4-Py-C (O) OCH ₂ CH (OH) CH (OH) CH (OH) CH (OH) CH ₂ OH.

Details of the synthesis of an isonicotinic acid-based organic ligand with propane-2,3-diol-1-amino-group 4-Py-C (O) NHCH (OH) CH ₂ OH: 1 g of isonicotinic acid chloride and 5.11 g of 3- aminopropane-1,2-diol is dissolved in 20 ml of dimethylformamide and placed in an oven for 84 hours at 100 ° C. At the end of the reaction, the reaction mixture was concentrated and filtered through a small layer of silica gel (eluent: mixture of chloroform and ethanol). The solvent was evaporated to give 4-Py-CONHCH (OH) CH ₂ OH as an oil. Yield: 1.04 (95%).

¹ H NMR (500 MHz, DMSO-d ₆ , ppm): 2.969 (m, 2H, NCH ₂ ), 3.1-3.4 (m, 3H, OCH, OCH ₂ ), 4.51 ( broad s, 1H, OH), 4.74 (broad s, 1H, OH), 7.732 (m, pyridyl fragment), 8.686 (m, pyridyl fragment). NMR (nuclear magnetic resonance) ¹³ C (500 MHz, DMSO-d ₆ , ppm): 41.34 (NCH ₂ ), 64.31 (OCH ₂ ), 70.86 (OCH), 121.86 ( CH pyridyl fragment), 142.15 (C pyridyl fragment), 150.73 (NCH pyridyl fragment), 162.01 (CO).

Similar to the synthesis of an organic ligand based on isonicotinic acid with a propane-2,3-diol-1-amino group 4-Py-C (O) NHCH (OH) CH ₂ OH, the synthesis of organic ligands based on:

- isonicotinic acid with propan-1,3-diol-2-amino-group 4-Py-C (O) NHCH (CH ₂ OH) ₂ ;

- based on nicotinic acid with propan-2,3-diol-1-amino-group 3-Py-C (O) NHCH (OH) CH ₂ OH;

- based on nicotinic acid with propan-1,3-diol-2-amino-group 3-Py-C (O) NHCH (CH ₂ OH) ₂ .

Synthesis of an isonicotinic acid-based organic ligand with 6- (4,6-bis- (hexane-2,3,4,5,6-pentaol-1-hydroxy) -1,3,5-triazine) -hexane-2, 3,4,5, -pentaol-1-hydroxy-group 4-Ru-C (O) OCH ₂ CH (OH) CH (OH) CH (OH) CH (OH) CH ₂ O [C ₃ N ₃ ] ( OCH ₂ CH (OH) CH (OH) CH (OH) CH (OH) CH ₂ OH) ₂ : 10.47 g [C ₃ N ₃ ] (OCH ₂ CH (OH) CH (OH) CH (OH) CH (OH) CH ₂ OH) _{3 is} dissolved by heating to 140 ° C. in 25 ml of dimethylformamide. The mixture was cooled to 120 ° C and 2.41 g of tripropylamine was added. Cool the mixture to 100 ° C and add a solution of 1.5 g of isonicotinic acid chloride in 5 ml of dimethylformamide. Incubated at 100 ° C for an hour. Then the solvent was evaporated. It is treated with acetone and ethanol and [C ₃ N ₃ ] (OCH ₂ CH (OH) CH (OH) CH (OH) CH (OH) CH ₂ OH) _{3 is} filtered off. Ethanol is evaporated and the reaction mixture is treated with ethyl acetate. Yield: 2.14 g (35%).

According to the data of elemental analysis for C ₂₇ H ₄₂ N ₄ O ₁₉ experimentally found mass content of elements (%): C 44.6; H 5.8; N, 7.7; theoretical mass content of elements (%): C 44.8; H 5.9; N, 7.8.

Synthesis of an organic ligand based on nicotinic acid with 6- (4,6-bis- (hexane-2,3,4,5,6-pentaol-1-hydroxy) -1,3,5-triazine) -hexane-2, 3,4,5, -pentaol-1-hydroxy-group 3-Ru-C (O) OCH ₂ CH (OH) CH (OH) CH (OH) CH (OH) CH ₂ O [C ₃ N ₃ ] ( OCH ₂ CH (OH) CH (OH) CH (OH) CH (OH) CH ₂ OH) _{2 is} carried out similarly to the synthesis of an organic ligand based on isonicotinic acid with 6- (4,6-bis- (hexane-2,3,4 , 5,6-pentaol-1-hydroxy) -1,3,5-triazine) -hexane-2,3,4,5, -pentaol-1-hydroxy-group 4-Ru-C (O) OCH ₂ CH (OH) CH (OH) CH (OH) CH (OH) CH ₂ O [C ₃ N ₃ ] (OCH ₂ CH (OH) CH (OH) CH (OH) CH (OH) CH ₂ OH) ₂ .

Details of the synthesis of an organic ligand based on a Schiff base derived from 4-pyridinaldehyde with the tris (hydroxymethyl) methyl group 4-Py-CH = NC (CH ₂ OH) ₃ : a small amount of a solution of 4-pyridinaldehyde (1.77 g) methanol is slowly added to a solution of tris- (hydroxymethyl) aminomethane (2 g) (reagent ratio 1: 1) in water. The reaction mixture was stirred at room temperature until a precipitate formed. The precipitate is separated from the solution, washed successively with cold water, ethanol, diethyl ether. The resulting compound was recrystallized from ethanol or methanol. The product yield is 90%.

IR spectrum (KBr): ν _max = 3500-3100 (OH, NH), 1612, 1488 (arom.) Cm ^-1 .

¹ H NMR (400 MHz, [D6] DMSO (dimethyl sulfoxide)): δ = 8.57 (d, J = 4.0 Hz, 2 H, H-arom.), 7.42 (d, J = 4, 8 Hz, 2 H, H-arom.), 5.43 (d, J2-H, NH = 10.8 Hz, 1 H, 2-H), 4.84 (br.s, 2 H, OH) , 3.70 (d, J = 8.0 Hz, 1 H, CH ₂ , ring), 3.67 (d, J = 8.0 Hz, 1 H, CH ₂ , ring), 3.44 (s , 2 N, CH ₂ ), 3.41 (d, J = 11.2 Hz, 1 N, CH ₂ ), 3.32 (d, J = 11.2 Hz, 1 N, CH2), 2.96 (d, JNH, 2-H = 10.8 Hz, 1 N, NH) ppm ¹³ C NMR (nuclear magnetic resonance): δ = (100 MHz, [D6] DMSO (dimethyl sulfoxide)): 149.6, 149.1, 121.2 (C arom.), 90.0 (C-2) 69.1 (C-5), 67.3 (C-4), 62.7, 62.4 (2C, CH ₂ ) ppm. According to elemental analysis for C ₁₀ H ₁₄ N ₂ O ₃ experimentally found mass content of elements (%): C 57.1; H 6.7; N 13.3; theoretical mass content of elements (%): C 57.1; H 6.7; N 13.2.

Similar to the synthesis of an organic ligand based on a Schiff base obtained from 4-pyridinaldehyde with a tris (hydroxymethyl) methyl group 4-Py-CH = NC (CH ₂ OH) ₃ , the synthesis of organic ligands is carried out:

- based on Schiff base derived from 3-pyridinaldehyde with tris- (hydroxymethyl) methyl group 3-Py-CH = NC (CH ₂ OH) ₃ ;

- based on Schiff base obtained from 4-pyridinaldehyde with 2,3-dihydroxypropyl group 4-Py-CH = NCH ₂ CH (OH) CH ₂ OH;

- based on Schiff base obtained from 3-pyridinaldehyde with 2,3-dihydroxypropyl group 3-Py-CH = NCH ₂ CH (OH) CH ₂ OH;

- based on Schiff base derived from 4-pyridinaldehyde with a bis- (hydroxymethyl) methyl group 4-Py-CH = NCH (CH ₂ OH) ₂ ;

- based on a Schiff base derived from 3-pyridinaldehyde with a bis- (hydroxymethyl) methyl group 3-Py-CH = NCH (CH ₂ OH) ₂ .

All experimental studies were carried out in accordance with the rules of Good Laboratory Practice, in accordance with legal and ethical standards for the treatment of animals. Biological toxicity testing of cluster compounds was carried out according to the following scheme:

Wistar male rats weighing 250-280 g were obtained, obtained from the vivarium of the Institute of Cytology and Genetics SB RAS, divided into 5 groups of 10 individuals. Before injection, all animals were weighed.

In the experimental groups, 2-3 ml of an aqueous solution of a cluster compound with an isonicotinic acid derivative with hexane-2,3,4,5,6-pentaol-1-hydroxy group [{Re ₆ S ₈ } (4-Ru-C) was injected intraperitoneally (O) OCH ₂ CH (OH) CH (OH) CH (OH) CH (OH) CH ₂ OH) ₃ ) ₆ ] Cl ₂ to achieve a total dose of 1 g / kg, 5 g / kg, 15 g / kg, 50 g / kg, in the control group used 2 ml of physiological saline. After 2 days of observation, surviving animals and animals of the control group were euthanized. A pathoanatomical study of all animals was carried out, then samples were taken for histological analysis. Rat survival after intraperitoneal administration of the cluster complex was 100% at a dose of 1 g / kg, 100% at a dose of 5 g / kg, 78% at a dose of 15 g / kg, 0% at a dose of 50 g / kg, 100% in the control group. The calculated LD ₅₀ was 42 g / kg. After administration of the drug at a dose of 50 g / kg in animals, general excitation, an increase in motor activity and respiratory rate, hyperemia of the limbs and auricles were observed. Then after 7-10 minutes, these phenomena disappeared.

During a pathological study of dead animals, no changes in internal organs were detected. A macroscopic examination of surviving animals revealed no pathological changes in the internal organs. In a histological examination of dead animals, pathological changes characteristic of general toxic damage were found only in the liver and kidneys. The remaining organs were unchanged. Histological studies of the remaining animals did not reveal differences from the control group.

In the experimental groups, 3-4 ml of an aqueous solution of a cluster compound with an isonicotinic acid derivative with hexane-2,3,4,5,6-pentaol-1-hydroxy-group [{Re ₆ Se ₈ } (4-Ru-C) were injected intraperitoneally (O) OCH ₂ CH (OH) CH (OH) CH (OH) CH (OH) CH ₂ OH) ₃ ) ₆ ] Cl ₂ to achieve a total dose of 1 g / kg, 5 g / kg, 15 g / kg, 50 g / kg, in the control group used 4 ml of physiological saline. After 2 days of observation, surviving animals and animals of the control group were euthanized. A pathomorphological examination of all animals was carried out, then samples were taken for histological analysis. Rat survival after intraperitoneal administration of the cluster complex was 100% at a dose of 1 g / kg, 99% at a dose of 5 g / kg, 74% at a dose of 15 g / kg, 1% at a dose of 50 g / kg. In the control group, the survival rate was 100%. The calculated LD ₅₀ was 39 g / kg. After administration of the drug in a high dose of 50 g / kg in animals, pronounced agitation, an increase in motor activity and respiratory rate, an increase in temperature and redness of the limbs and auricles were observed. Then after 7-10 minutes, these phenomena disappeared. A comparative analysis of the histological material of the remaining groups of animals and the control group did not reveal differences.

According to physicochemical parameters, the analogue of cluster compounds is the isosmolar iodine-containing X-ray contrast drug Visipack-320 (Nycomed, Austria). It is known that a 50% lethal dose for Visipack is 24.2 g of iodine / kg body weight. The estimated 50% lethal dose of the cluster compound is 42 g / kg, which proves its lower toxicity compared to a commercially available analogue.

The technical result is to reduce the toxicity of the radiopaque substance and, as a consequence, to reduce the likelihood of a contrast inducing nephropathy. A unique feature of the invention is electroneutrality and the presence of a biologically safe ligand environment with hydrophilic nonionic functional groups, which ensures isosmolarity to physiological fluids. It is possible to reduce the administered dose of the drug.

Claims (2)

1. X-ray contrast substance corresponding to the formula:
[{Re ₆ Q ₈ } L ¹ _n L ² _m X _6-nm ] ^q ,
containing an octahedral cluster core {Re ₆ Q ₈ }, where: Q - S or Se;
n is 0, 1, 2, 3, 4, 5, or 6; m is 0, 1, 2, 3, 4, 5, or 6; n + m = 0, 1, 2, 3, 4, 5, or 6; q = 4-, 3-, 2-, 1-, 0, 1+ or 2+; X is a singly charged anionic ligand of organic or inorganic nature, and is selected from the series: F ^- , Cl ^- , Br ^- , I ^- , CN ^- , SCN ^- , SeCN ^- , OH ^- , NO ^- , NO ₂ ^- , NO ₃ ^- , SH ^- , CF ₃ ^- , H ₂ PO ₄ ^- , H ₂ PO ₃ ^- , H ₂ PO ₂ ^- , HRCOO ^- or RSO ₃ ^- , where R is the limiting or unsaturated aliphatic or aromatic residue, including containing fluorine, consisting from: —H, —CH ₃ , —CH ₂ CH ₃ , —CH ₂ CH ₂ CH ₃ , —CH (CH ₃ ) ₂ , —CH ₂ CH ₂ CH ₂ CH ₃ , —CH ₂ CH (CH ₃ ) ₂ , -CH (CH ₃ ) CH ₂ CH ₃ , -C (CH ₃ ) ₃ , -C ₆ H ₅ , -C ₆ H ₄ CH ₃ , -C ₅ H ₄ N, -CF ₃ , -CF ₂ CF ₃ , -CF ₂ CF ₂ CF ₃ , -F (CF ₃ ) ₂ , -CF ₂ CF ₂ CF ₂ CF ₃ , -F ₂ CF (CF ₃ ) ₂ , -CF (CF ₃ ) CF ₂ CF ₃ , -C (CF ₃ ) ₃ , -C ₆ F ₅ ; a L ¹ and L ² denote pyridine-containing ligands that are bound to the cluster core via a Re-N bond and are selected from a number of nicotinic or isonicotinic acid derivatives containing, in the composition of the group R1: hydroxy- or amino- or diethanolamino- or propane -2,3-diol-1-amino, or propan-1,3-diol-2-amino, or 2-hydroxymethyl-propan-1,3-diol-2-amino, or hexane-2,3 4,5,6-pentaol-1-hydroxy- or 6- (4,6-bis- (hexane-2,3,4,5,6-pentaol-1-hydroxy) -1,3,5-triazine ) -hexane-2,3,4,5, -pentaol-1-hydroxy group; or selected from a number of derivatives of 4-pyridinaldehyde or 3-pyridinaldehyde containing in the group R2: tris- (hydroxymethyl) methyl or 2,3-dihydroxypropyl or bis- (hydroxymethyl) methyl groups. 2. X-ray contrast substance corresponding to the formula:
[{Re ₆ Q ₈ } L ¹ _n L ² _m Y _6-nm ] ^q ,
containing an octahedral cluster core {Re ₆ Q ₈ }, where: Q - S or Se;
n is 0, 1, 2, 3, 4 or 5; m is 0, 1, 2, 3, 4 or 5; n + m = 0, 1, 2, 3, 4 or 5; q = 10-, 8- 6-, 4-, 2- or 0; Y is a doubly charged anionic ligand of organic or inorganic nature, and is selected from the group consisting of: SO ₃ ^2- , S ₂ O ₃ ^2- , SeSO ₃ ^2- , SeO ₃ ^2- , HPO ₄ ^2- , HPO ₃ ^2- , C ₂ O ₄ ^2- , ^- OOC- (M) _n -COO ^- , where n = 0-6, and M is the limit or unsaturated aliphatic or aromatic residue, including containing fluorine; and L ¹ and L ² are pyridine-containing ligands that are linked to the cluster nucleus via a Re-N bond and are selected from a number of nicotinic or isonicotinic acid derivatives containing, in the composition of the R1 group: hydroxy or amino groups; or selected from a number of derivatives of 4-pyridinaldehyde or 3-pyridinaldehyde containing in the group R2: tris- (hydroxymethyl) methyl or 2,3-dihydroxypropyl or bis- (hydroxymethyl) methyl groups.