New tetrakis-guanidinium-containing p-tert-butylthiacalix[4]arene forms monodisperse nanoparticles with diameter 44 nm in the concentration range of 40-100 μm. Its association constant with model DNA was evaluated as pK a = 3.96 by fluorescent intercalator displacement assay. © 2014 Mendeleev Communications. All rights reserved

Galukhin A.

Stoikov I.

Mendeleev Communications

Kazan Federal University Digital Repository

Mendeleev Commun., 2014, 24, 82–84– 82 –© 2014 Mendeleev Communications. All rights reserved.MendeleevCommunicationsMolecular design of synthetic receptors that can effectively interact with anionic and polyanionic biomacromolecules is an important goal of supramolecular chemistry.1–4 Using macro­cyclic platforms such as calixarenes able to spatially organize binding sites makes it possible to obtain effective antibacterial drugs,5 transfection agents6 and artificial enzymes.7Creation of nanoparticles with surface functional groups providing affinity toward different biomacromolecules attracts attention of many scientists. Such particles offer opportunities to development of drug delivery systems, DNA transfection, diag­nostics tools and protein separation.8–11 Guanidinium frag ments provide the greatest affinity of the nanoparticles to poly anionic substrates.12,13 The efficiency of interaction of a guani dinium moiety with anionic substrates, such as carboxylate and phosphate groups, is due to their geometrical and charge complementarity.1Despite the relevance, there are no examples in the literature describing the synthesis of guanidinium­containing thiacalix[4]­arenes which have a greater conformational and synthetic potential against classical calix[4]arenes.14–20For the preparation of guanidinium­containing p-tert­butyl­thiacalix[4]arenes the previously described amino derivatives 1 and 221,22 were tested as the starting reactants. Traditional reagents such as 3,5­dimethyl­1H­pyrazole­1­carboxamidine nitrate, cyan­amide and isothiouronium salts previously used for introduction of the guanidinium fragments into non­macrocyclic derivatives appeared to be ineffective in the case of derivatives 1 and 2. In all the cases, a complex mixture of partially functionalized products was obtained.To access the target compounds, we turned to more effective diprotected triflyl guanidines.23 In the two­step synthesis, amines 1, 2 were treated with N,N'­bis(tert­butoxycarbonyl)­N''­triflyl­guanidine and then the resulting Boc­derivatives 3, 4 were deprotected using hydrochloric acid (Scheme 1).†Interestingly, the rate of removal of the tert­butoxycarbonyl protecting groups in 3 and 4 differs greatly. In the case of tetra­substituted at the lower rim p-tert­butylthiacalix[4]arene 4, the deprotection proceeded within 24 h affording a water soluble compound 7 in high yield. In the case of compound 3 with free phenolic groups at the lower rim, the reaction mixture after 24 h consisted of the target compound 6 along with the mono­Boc­derivative 5 in the ratio 5 : 6 of 45 : 55. Compound 5 was isolated by preparative column chromatography and characterized.Such an unexpected difference in the reactivity of compounds 3 and 4 can be explained by the presence of free phenolic groups Guanidine-equipped thiacalix[4]arenes: synthesis,  interaction with DNA and aggregation propertiesAndrey V. Galukhina and Ivan I. Stoikov*a,ba A. M. Butlerov Institute of Chemistry, Kazan (Volga Region) Federal University, 420008 Kazan,  Russian Federation. Fax: +7 843 233 7416; e-mail: Ivan.Stoikov@mail.rub Kazan Institute of Biochemistry and Biophysics, Kazan Scientific Centre of the Russian Academy  of Sciences, 420111 Kazan, Russian Federation DOI: 10.1016/j.mencom.2014.03.005New tetrakis-guanidinium-containing p-tert-butylthiacalix[4]arene forms monodisperse nanoparticles with diameter 44 nm in the concentration range of 40–100 mm. Its association constant with model DNA was evaluated as pKa = 3.96 by fluorescent intercalator displacement assay. R2OOHHNNNHHHHHR1 OPOO ONNNHHHR1 R3H............HHS SButBut ButOOO OSButSRHNHNHNTfOButButOO O1NHNBocNHBocOROS SOButOSSButButButRRR21, 2  R = NH23 (77%) 4 (98%)CH2Cl2 CH2Cl23, 4  R =NHNHNHBoc    5  R =NHNH2NH26, 7  R =HClTHF5 (30%) 7 (80%)HClTHF6 (55%)HCl THFCl–Scheme 1† Compounds 3 and 4. The stoichiometric amount of N,N'­bis(tert­but oxy­carbonyl)­N''­triflylguanidine in 20 ml of dichloromethane was added to the solution of 1.00 g of corresponding compound 1, 2 in 40 ml of dichloromethane in one portion at room temperature. After 24 h, the mixture was washed with 2 m aqueous NaHSO4 (10 ml) and saturated NaHCO3 (10 ml). Each aqueous layer was extracted with dichloromethane (2×10 ml). The combined organic phases were washed with brine (10 ml), dried (MS 3 Å), filtered and concentrated under reduced pressure.

Guanidine-equipped thiacalix[4]arenes: Synthesis, interaction with DNA and aggregation properties

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Guanidine-equipped thiacalix[4]arenes: Synthesis, interaction with DNA and aggregation properties

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