Center for Magnetic Resonance

E.A. Popova, T.V. Serebryanskaya, S.I. Selivanov, M. Haukka, T.L. Panikorovsky, V.V. Gurzhiy, I. Ott, R.E. Trifonov, V.Yu. Kukushkin

“Water soluble platinum(II) complexes featuring 2-alkyl-2H-tetrazol-5-ylacetic acids: synthetic, X-ray diffraction, and solution NMR studies”

Eur. J. Inorg. Chem., 2016, 28, 4659-4667
DOI:10.1002/ejic.201600626

2-R-2H-Tetrazol-5-ylacetic acids (abbreviated as 2-R-taa; R = Me, iPr, tBu) react with K₂[PtCl₄] in 1 m HCl in H₂O at r.t. furnishing trans-platinum(II) complexes trans-[PtCl₂(2-R-taa)₂] (1–3), whereas cis-isomeric species cis-[PtCl₂(2-R-taa)₂] (R = iPr, 4; tBu, 5) are isolated at lower temperature (4–6 °C). In the presence of EtOH in the reaction mixture, esterification of the tetrazol-5-ylacetoxy group of 2-tBu-taa leads to trans-[PtCl₂(ethyl 2-tert-butyl-2H-tetrazol-5-ylacetate)₂] (6). Complexes 1–6 were characterized by elemental analyses (CHN), HRESI+-MS, ¹H, ¹³C{1H}, ¹⁹⁵Pt{1H} NMR and IR spectroscopy, differential scanning calorimetry/thermogravimetry (DSC/TG), and X-ray diffraction (for 1·H2O, 2, 3·2H2O, 4, 5·2H₂O, and 6). The generation of the tetrazole-based complexes in solution (1 m DCl in D2O, 25 °C) was studied by ¹H NMR spectroscopy and HPLC-MS. The obtained data indicate the initial formation of anionic [PtCl₃(2-R-taa)]– complexes that are subsequently converted into disubstituted isomeric platinum(II) species cis- and trans-[PtCl₂(2-R-taa)₂]. By contrast to cis- and trans-[PtCl₂(2-R-taa)₂] that were inactive in two human cancer models in vitro (IC50 > 100 µm), complex 6 demonstrated noticeable antiproliferative effects in HT-29 colon and MCF-7 breast carcinoma cell lines with IC50 values of 14.2 ± 1.1 and 5.8 ± 1.2 µm, respectively.

A.S. Mikherdov, M.A. Kinzhalov, A.S. Novikov, V.P. Boyarskiy, I.A. Boyarskaya, D.V. Dar’in, G.L. Starova, V.Yu. Kukushkin

“Difference in energy between two distinct types of chalcogen bonds drives regioisomerization of binuclear (Diaminocarbene)PdII complexes”

J. Am. Chem. Soc., 2016, 138, 14129-14137
DOI:10.1021/jacs.6b09133

The reaction of cis-[PdCl₂(CNXyl)₂] (Xyl = 2,6-Me₂C₆H₃) with various 1,3-thiazol- and 1,3,4-thiadiazol-2-amines in chloroform gives a mixture of two regioisomeric binuclear diaminocarbene complexes. For 1,3-thiazol-2-amines the isomeric ratio depends on the reaction conditions and kinetically (KRs) or thermodynamically (TRs) controlled regioisomers were obtained at room temperature and on heating, respectively. In CHCl3 solutions, the isomers are subject to reversible isomerization accompanied by the cleavage of Pd–N and C–N bonds in the carbene fragment XylNCN(R)Xyl. Results of DFT calculations followed by the topological analysis of the electron density distribution within the formalism of Bader’s theory (AIM method) reveal that in CHCl₃ solution the relative stability of the regioisomers (ΔGexp = 1.2 kcal/mol; ΔGcalcd = 3.2 kcal/mol) is determined by the energy difference between two types of the intramolecular chalcogen bonds, viz. S···Cl in KRs (2.8–3.0 kcal/mol) and S···N in TRs (4.6–5.3 kcal/mol). In the case of the 1,3,4-thiadiazol-2-amines, the regioisomers are formed in approximately equal amounts and, accordingly, the energy difference between these species is only 0.1 kcal/mol in terms of ΔGexp (ΔGcalcd = 2.1 kcal/mol). The regioisomers were characterized by elemental analyses (C, H, N), HRESI+-MS and FTIR, 1D (¹H, ¹³C{1H}) and 2D (¹H,¹H-COSY, ¹H,¹H-NOESY, ¹H,¹³C-HSQC, ¹H,¹³C-HMBC) NMR spectroscopies, and structures of six complexes (three KRs and three TRs) were elucidated by single-crystal X-ray diffraction.

T.B. Anisimova, M.A. Kinzhalov, M.L. Kuznetsov, M.F.C. Guedes da Silva, A.A. Zolotarev, V.Yu. Kukushkin, A.J.L. Pombeiro, K.V. Luzyanin

“1,3-Dipolar cycloaddition of nitrones to gold(III)-bound isocyanides”

Organometallics, 2016, 35, 3569-3576
DOI:10.1021/acs.organomet.6b00635

Treatment of gold(III)-isocyanides [AuCl₃(CNR₁)] (R₁ = Xyl 1, Cy 2, But 3) with an equimolar amount of 5,5-dimethyl-1-pyrroline-N-oxide (4) in CH2Cl2 at −74 °C leads to the generation of the heterocyclic aminocarbene species [AuCl₃{C(ON^aCMe₂CH₂CH₂C^bH)═N^eR1}(N^a–C^b)(C^b–N^e)] 8 (for R₁ = But) or gold(III) complexes cis-[AuCl₂{N^a(CMe₂CH₂CH₂C^bN^eR₁)C^d═O}(N^a═C^b)(N^e–C^d)] 9 and 10 (for R₁ = Xyl and Cy) in good isolated yields (75–87%). DFT calculations show that deprotonation of the endocyclic CH group in the carbene ligand leads to spontaneous N–O bond cleavage, and acidity of this group is a factor controlling the different chemical behavior of 1–3 depending on the nature of substituent R1. The reaction of equimolar amounts of the aldonitrone p-TolCH═N⁺(Me)O^– (5) or the ketonitrones Ph₂C═N⁺(R₂)O^– (R₂ = Ph 6, CH₂Ph 7) with 1–3 in CD2Cl2 at −70 °C in air (or under N2) revealed the formation of the carbene complexes [AuCl₃{C(ONMeC^aH-p-Tol)═N^bR₁}(C^a–N^b)] (R₁ = Cy 11, Xyl 12, But 13), [AuCl₃{C(ONPhCaPh₂)═N^bR₁}(Ca–N^b)] (R₁ = Cy 14, But 15), or [AuCl₃{C(ON(CH₂Ph)C^aPh2)═N^bR₁}(C^a–N^b)] (R₁ = Cy 16, Xyl 17), as studied by ¹H NMR. The reaction of 6 with 1 and of 7 with 3 did not furnish carbene products. Compounds 8–10 were characterized by ESI-MS, IR, 1D (¹H, ¹³C{H}) and 2D (¹H,¹H–COSY, ¹H,¹³C-HSQC, ¹H,¹³C-HMBC) NMR spectroscopic techniques, and, only for 8, elemental analyses (C, H, N), while compounds 11–17 were characterized by 1D (¹H, ¹³C{H}) and 2D (¹H,¹³C-HSQC) NMR. Structures of compounds 8, 9, and 13 were additionally established by single-crystal X-ray diffraction.

D.S. Bolotin, A.S. Novikov, V.K. Burianova, M.Ya. Demakova, E.A. Daines, С. Pretorius, P. Mokolokolo, A. Roodt, N.A. Bokach, M.S. Avdontceva, A.P. Zhdanov, K.Yu. Zhizhin, N.T. Kuznetsov, V.Yu. Kukushkin

“Nucleophilicity of oximes based upon addition to а nitrilium closo-decaborate cluster”

Organometallics, 2016, 35, 3612-3623
DOI:10.1021/acs.organomet.6b00678

Three types of oxime species, i.e., 4-morpholylcarbamidoxime (hydroxyguanidine), phenylacetamidoxime and benzamidoxime (amidoximes), and cyclohexanone oxime and benzophenone oxime (ketoximes), react at room temperature with the 2-nitrilium closo-decaborate clusters, leading to 2-iminium closo-decaborates (14 examples; 57–94%). These species were characterized by ICPMS-based boron elemental analysis, HRESI–-MS, molar conductivity, IR, 1H{11B}, and 11B{1H} NMR spectroscopies, and additionally by single-crystal X-ray diffraction (for six compounds). On the basis of kinetic data, ΔH⧧, ΔS⧧, and ΔG⧧ of the additions were determined, showing a 4 order-of-magnitude decrease in reactivity from the hydroxyguanidine to the aromatic ketoxime as entering nucleophiles. The results of DFT calculations indicate that the mechanism for these reactions is stepwise and is realized through the formation of the orientation complex of the nitrone form, R2R3C═N+(H)O–, of oximes with [B10H9NCEt]−, giving further an acyclic intermediate (the rate-determining step), followed by proton migration, leading to the addition product. The calculated overall activation barrier for these transformations is consistent with the experimental kinetic observations. This work provides, for the first time, a broad nucleophilicity series of oximes, which is useful to control various nucleophilic additions of oxime species.