A.E.Arbuzov Institute of Organic & Physical Chemistry, Kazan A.M.Butlerov Chemistry Institute of Kazan Federal University, Kazan Supramolecular chemistry of (thia)calix[4]arenes Lviv, 6-10 September 2010 I.S.Antipin, S.E.Solovieva, I.I.Stoikov, A.I.Konovalov

Moscow Kazan Novosibirsk St.Petersbourg V International symposium “Design and Synthesis of Supramolecular Architectures” October 2009 VI International symposium “Design and Synthesis of Supramolecular Architectures” September 18-23,

Basic principle of supramolecular chemistry Jonathan Swift Macrocycles– molecular platform for multipoint interactions realization and multivalent ligands design.

Macrocyclic platforms

Calixarenes Calyx CPK- Model X X X X HH H H S S S S X X X X HH H H X=O, S, NH

Calix[4]arenes The characteristic advantages of calix[4]arenes for the constructing of receptors are followed:  the low cost and accessibility of parent macrocycles by one-pot synthesis;  calixarenes can incorporate the small hydrophobic organic molecules into their molecular cavities with the formation of the stable host-guest complexes;  the existence of variety of calixarene conformations: cone, partial cone, 1,2-alternate, 1,3-alternate etc.;  calix[4]arene conformations are rather rigid and are able to fix the required spatial orientation of binding centers;  nontoxicity of calixarene platforms.  calixarene platform gives an unique possibility to decorate the upper and lower rim of macrocycle by the suitable heteroatom groups and to form the molecular system possessing the several binding centers; 1997 – S.Miyano et al Thiacalix[4]arene O O O O H H H H O H H O H O O H O O H H H O H O O O H H H O H O Cone Partial Cone V≈10A 3 1,3-Alternate 1,2-Alternate

Background of Calixarene Chemistry Main Problem: Stereo and Regio Selective Functionalization of Lower and Upper Rim S S S S OH OH OH O H Upper Rim Lower Rim Mono, Di, Tri and Tetra Substituted Derivatives O O O O R R R R O R R O R O O R O O R R R O R O Cone Partial Cone 1,3-Alternate 1,2-Alternate O O R R R O R O

1. Covalent assembly: towards nanosized molecules 2. Nonc ovalent assembly: towards “soft” nanosystems 2 n + n Functions Receptor - signal Phototransforming – accumalation hνhν “guest quenching Outline

Y= B, Ge, Sn, Sb, M n+ = Fe 2+, Co 2+, Co 1+, Ru 2+ R = Hal, Ar, Alk, XAr, XAlk, Z =F, Alk, Ph Clathrochelates – tris-dioximates The characteristic advantages of macrobicyclic tris-dioximates:  accessibility by one or two-step synthesis;  stability in acidic and alkaline media;  metal ability to redox processes inside of the ligand cavity;  the possibility of side and apical position functionalization.

M n+ Cl S S SH O S O S HS O O S S S O S S O S S S O O M n+ M n+ Guest 1,3-Alternate M n+ Cl SH O O S S SS S S O O S S S S M n+ Guest Design of new types of cavitands: conjugates of clathrochelate and thiacalixarenes Route b Route a Cone

Where we are going?

+ S O O O O S S S B O O O N N N N O B O O N N FeFe F F (CH 2 )n S (CH 2 )n (CH 2 )n (CH 2 )n S S S B O O O N N N N O B O O N N FeFe F F n=3, 4, 5 2+ Yield: n=3: 0% n=4: 58% n=5: 2% Synthesis calixarene/clathrochelate conjugates: effect of methylene spacer length

Synthesis calixarene/clathrochelate conjugates: effect of methylene spacer length N=3, Yield 20% N=5, Yield 65%

Nanoparticles size (nm) /Polydispersity Free ligandLi+Ag+ Cone / 0.18 Cone / / 0.08 Paco / 0.16 Paco / 0.17 Alternate / 0.19 Alternate / 0.23 Extraction data C (Ме n+ ) = 0,1M, C(L) = *10 -3 M, С(Pic - ) = 2.3*10 -4 M Li + Ag + nLogK ex E%nLogK ex E% Cone Cone Paco Paco Alternate Alternate R = N O R = N 5 6 Cone Paco 1,3-Alternate Noncovalent assembly of nanoaggregates

16 3 hours 28 hours + Ag + Nanoparticles size distribution of Ag complex in CH 2 Cl 2 Paco-7

SEM nanoparticles image of Ag(I) complex in CH2Cl2 17 1,3-alt - 10

6a6b6c Li Na K+K+ 012 Cs Al Fe Ni 2+ 5 Cu Co Ag + 8 Pb Hg 2+ 0 Cd The size of the aggregates formed thiacalix[4]arenes, functionalized with hydrazide groups, with metal cations

UV spectra (510 –6 mol L –1, 1cm cell) of p-tert butyl thiacalix[4]arene in the trans (1) and cis (2) forms in dichloromethane Photo-switching of thiacalix[4]arene derivative 1 containing azobenzene moieties

Photo-switchable self-assembly of nanosized aggregates

hν (254 nm) Model of photo-switchable self-assembly: first step from the inanimate to living matter

Magnetic Resonance Imaging (MRI) Relaxivity R 1 p ~ M -1 s -1, lgβ ~ Commercial contrast agents Main approaches to relaxivity enhancement: - the induction of steric hindrance around the water binding site; - the rise of the complex molecular mass due to aggregation.

Effect of macrocycle conformation on Gd(III) relaxivity cone paco 1,3-alt TC[4] Ac

Acknowledgment Scientific team in KFU Prof. I.I.Stoikov Dr.O.A.Mostovaya A.Yu.Zhykov E.A.Yushkova E.A. Zaikov Grants Russian Foundation for Basic Research Russian Academy of Sciences Ministry of Education and Sciences RF CRDF Academician A.I.Konovalov Collaborators Prof. Ya.Z.Voloshin Prof. M.W.Hosseini Prof. R.R.Amirov Prof. A.R.Mustafina Prof. G.A.Evtyugin Dr. E.E.Stoikova Dr. A.T.Gubaidullin Scientific team in IOPC Dr. S.E.Solovieva Dr. E.A.Popova Dr. S.R.Kleshnina Dr. M.N.Kozlova Dr.A.A.Tuyftin