Nicoletta Nardi

Small aza cages as “fast proton sponges” and strong lithium binders

The design and synthesis of new compounds in order to achieve expected or new chemical properties is one of the most fascinating aspects of modern synthetic chemistry. Among the many thousands of new compounds synthesized each year, macrocyclic compounds play an important role. The ever growing interest in this very active field stems from different points of view, including selective ion recognition, transport processes, reaction catalysis, industrial applications, model systems, and others [l-17]. Numerous books on macrocyclic chemistry have been published in the last few years [18-27]. Molecular topology and the nature of donor atoms are the two most important parameters influencing the chemical properties of macrocyclic compounds. Different classes of synthetic macrocyclic compounds have been developed and, in addition to the most studied crown-ether family, the aza-crowns are the next most studied class of synthetic macrocycles [ 19,251. These compounds could be considered to be derived from crown ethers by replacing the oxygen donor atoms with softer nitrogen donor atoms. The presence of this kind of donor atom makes these compounds water soluble bases and very prone to bind transition metal ions [28,29].

Complexes of cobalt(II), nickel(II), copper(II), and zinc(II) with the tripod-like ligands tris (2-methylthioethyl)amine

Abstract The preparation and properties of nine complexes formed by the quadridentate ligand tris(2-methylthioethyl)amine, TSN, and the halides or thiocyanate of cobalt(II), nickel(II), copper(II), and zinc(II) have been studied. The cobalt complexes are formulated as [CoX(TSN)] 2 [CoX 4 ] thus containing both high-spin five-coordinated cobalt and tetrahedral cobalt. The compounds NiX 2 (TSN) are octahedral and [CuBr(TSN)]Br is five-coordinated. Zinc iodide forms the monomeric compound Znl 2 (TSN).

1,10-Dimethyl-1,4,7,10,13,16-hexaazacyclooctadecane L and 1,4,7-trimethyl-1,4,7,10,13,16,19-heptaazacyclohenicosane L1: two new macrocyclic receptors for ATP binding. Synthesis, solution equilibria and the crystal structure of (H4L)(ClO4)4

The synthesis of two new methylated ligands 1,10-dimethyl-1,4,7,10,13,16-hexaazacyclooctadecane L and 1,4,7-trimethyl-1,4,7,10,13,16,19-heptaazacyclohenicosane L1 is described. Basicity constants and protonation enthalpies of both ligands have been determined by potentiometric and microcalorimetric measurements in 0.15 mol dm–3 NaClO4 at 298.1 K. The protonated forms of these cyclic polyamines bind ATP in solution. The equilibrium constants of the species formed have been determined (0.15 mol dm–3 NaClO4, 298.1 K). The results presented for L and L1 are compared with those previously obtained for the related ligands 1,4,7,10,13,16-hexaazacyclooctadecane, 1,4,7,10,13,16,19-heptaazacyclohenicosane and 1,4,7,13-tetramethyl-1,4,7,10,13,16-hexaazacyclooctadecane. Among these macrocycles Lis a selective receptor for ATP binding.The crystal structure of the compound (H4L)(ClO4)4[space group P21/c, a= 9.257(4), b= 8.600(2). c= 17.990(10)A, β= 101.74(4)°, V= 1402(1)A3, Z= 2] shows that the four charged ammonium groups point inside the macrocyclic cavity.

Proton inclusion properties of a new azamacrocycle. Synthesis, characterization and crystal structure of [H3L][Cl]3·2H2O (L = 4,10-dimethyl-1,4,7,10-tetraazabicyclo [5.5.2] tetradecane)

Abstract Macrocyclic compounds have been extensively investigated, the interest for this huge class of compounds spans from fundamental research to specific industrial applications. 1 – 8 We have recently published a few papers on small macrocycles having cage-like molecular topology.9 – 19 They present special proton-transfer properties and in few cases they are strong, selective lithium binders in aqueous solution.14,15,17 The three-dimensional cavity present in these compounds is achieved by connecting two secondary nitrogen atoms of a tetraazamacrocycle with different bridging groups (see Fig 1). Molecular topology and nature of donor atoms are the most important elements influencing the chemical properties of this class of compounds. For these reasons we are continuing our investigations on these compounds by systematically changing the bridging unit; we report here the synthesis and chemical properties of the new cage 4,10-dimethyl-1,4,7,10-tetraazabicyclo[5.5.2]-tetradecane, abbreviated as L.

The small cage 12,17-dimethyl-5-oxa-1,9,12,17-tetra-azabicyclo[7.5.5]nonadecane (L): its synthesis, characterization, and ‘proton sponge’ behaviour. The crystal structure of the dipicrate salt [H2(L)](picrate)2

The synthesis and characterization of the new oxa-azamacrobicycloalkane 12,17-dimethyl-5-oxa-1,9,12,17-tetra-azabicyclo[7.5.5]nonadecane (L) are described. Its basicity behaviour in both aqueous and water–Me2SO (50:50 mol/mol) solutions has been investigated by potentiometric and spectroscopic (1H and 13C n.m.r.) techniques. In aqueous solution it behaves as a very strong base (proton sponge) in the first protonation step, and as a relatively strong base in the second step (log k2= 11.21). In the mixed water–Me2SO solvent both protonation constants have been measured: log k1= 14.0 and log k2= 8.2. 1H N.m.r. experiments indicate that in the monoprotonated species H(L)+ the proton is rapidly exchanged with acidic hydrogens on the n.m.r. timescale. 1H–1H and 1H–13C two-dimensional n.m.r. experiments allowed the unequivocal assignment for all the 1H proton and 13C resonances of both species H(L)+ and H2(L)2+. Crystals of [H2(L)](picrate)2 are monoclinic, space group P21/n, with a= 12.868(8), b= 17.201(2), c= 16.614(2)A, β= 110.18(1)°, and Z= 4; final R values of 0.090 (Rw= 0.090) for 3 801 observed reflections. The four basal nitrogen atoms and the apical oxygen atom are located at the apices of a slightly distorted square pyramid. X-Ray analysis shows that protonation occurs on the NCH3, groups. Each hydrogen atom of the NH+CH3 interacts with the oxygen atom, the 0 ⋯ H distances 2.328(16) and 2.112(18)A, and with both bridgehead nitrogen atoms, the H ⋯ N distances ranging from 2.32 to 2.34 A. This arrangement makes the overall structure very stable from the thermodynamic point of view and explains the unusually high basicity of (L) in both first- and second-protonation step.

Synthesis and characterization of an aza-cage behaving as a ‘proton sponge’. Crystal structures of its mono- and tri-protonated species

The synthesis and characterization of the new macrobicyclic cage 4,10-dimethyl-1,4,7,10-tetraazabicyclo[5.5.4]hexadecane L is reported. Its basicity behaviour in aqueous solution has been investigated by potentiometric (25 °C, I= 0.15 mol dm–3) and NMR (1H and 13C) techniques. It behaves as a very strong base (proton sponge) in the first protonation step, and as a moderate base in the second step (log K2= 7.8). 1H–1H and 1H–13C two-dimensional NMR experiments permitted the unequivocal assignment of all 1H proton and 13C resonances of both species HL+ and H2L2+. Furthermore NMR experiments indicate that the first protonation involves the bridgehead nitrogens. Crystals of [HL][ClO4] are orthorhombic, space group P21cn, with a= 9.044(2), b= 12.573(2), c= 16.126(3)A, and Z= 4; final R value of 0.089 (Rw= 0.086) for 1267 unique observed reflections with I > 3σ(I). X-Ray analysis shows that protonation occurs on the bridgehead nitrogen N(2) and an overall macrocyclic conformation with the all nitrogen atoms in the endoconfiguration. The short H(2)⋯(4)[1.69(1)A] and N(2)⋯ N(4)[2.75(1)A] distances indicate a strong hydrogen bond. H(2) further interacts with the other two tertiary nitrogens: H(2)⋯ N(1)[2.53(1)A] and H(2)⋯ N(3)[2.46(1)A]. This arrangement makes the monoprotonated species very stable from the thermodynamic point of view and explains the high basicity of L. Crystals of [H3L][ClO4]3 are tetragonal, space group P43212, with a= 8.498(2), b= 8.498(2), c= 32.855(8)A, and Z= 4; final R value of 0.083 (Rw= 0.093) for 1076 unique observed reflections with I > 3σ(I). The X-ray analysis shows an overall macrocyclic conformation with two nitrogen atoms in the endoconfiguration and two in exo configuration.

Selective Lithium Complexation by Photoactive Aza-Cages Bearing the Anthracene Function

Three aza-cages with the anthracene-containing photoactive groups L1, L2, and L3 have been synthesized. All compounds are able to selectively encapsulate a lithium ion and solid complexes have been isolated. The formation equilibria have been investigated by UV/Vis and 1H, 13C and 7Li NMR spectroscopic techniques. The fluorescence emission of both free ligands and lithium complexes have been investigated. Results indicate that the CHEF (chelation enhancement of the fluorescence) effect obtained by lithium coordination exits although lower than that occurring upon full protonation.

Synthesis and characterisation of the five diastereoisomers of 4,7,13,16-tetraphenyl-1,10-dithia-4,7,13,16-tetraphosphacyclo-octadecane: crystal structure of the nickel bromide complex of the β-isomer

The novel dithiatetraphospha-macrocycle 4,7,13,16-tetraphenyl-1,10-dithia-4,7,13,16-tetraphosphacyclo-octadecane (L2) has been synthesised in 14% yield via a one-step procedure. All of the five possible diastereoisomers were isolated, and two of them (α and β) used to form cobalt(II) and nickel(II) complexes. The compound [Ni(β-L2)]Br2·2H2O crystallises in a triclinic unit cell (P space group) with lattice Constants a= 9.645(3), b= 10.159(3), c= 10.869(3)A, α= 68.07(4), β= 78.09(4), γ= 84.69(4)°, and Z= 1. Least-squares refinement gave R= 0.059 for 1 395 observed reflections. The X-ray diffraction study of this complex shows that the nickel atom is six-co-ordinated by two sulphur and four phosphorus atoms of the macrocycle forming an elongated trans-octahedral geometry. The stereochemistry of the β isomer is 4RS,7RS,13SR,16SR. The 4RS,7RS,13RS,16SR isomer (α isomer) has been identified by 31P n.m.r. spectroscopy.

Synthesis and characterisation of 1,7-dimethyl-1,4,7,10-tetra-azacyclododecane: crystal structure of the nickel(II) bromide monohydrate complex of this macrocycle; thermodynamic studies of protonation and metal complex formation

The synthesis and characterisation of the macrocycle 1,7-dimethyl-1,4,7,10-tetra-azacyclododecane (L1) are reported. The basicity constants of L1 and the stability constant of the complex [CuL1]2+ have been determined by potentiometry at 25 °C in 0.5 mol dm–3 KNO3. The macrocycle L1 behaves as a diprotic base in the pH range investigated; pD–13C n.m.r. studies indicate that only the two secondary nitrogens are involved in the protonation process. Copper(II) and nickel(II) complexes with L1 have been prepared and studied spectrophotometrically both in aqueous solution and in the solid state. The reflectance spectrum of dry yellow NiL1(ClO4)2 shows that a square-planar geometry, with the nickel(II) in the low-spin state, is achievable also with this partially methylated twelve-macrocycle. The molecular structure of the complex [NiBr(H2O)L1]Br has been determined by single-crystal X-ray analysis. The compound crystallises in an orthorhombic unit cell (space group P212121) with lattice constants a= 13.478(5), b= 11.186(4), and c= 10.585(4)A for Z= 4. Least-squares refinement converged at R= 0.046 for 910 observed reflections. The complex shows a cis-octahedral geometry, with the macrocycle co-ordinated in a folded configuration to four sites around the central nickel atom. The chirality of each nitrogen atom of the macrocycle is the same. The bromide ion and the oxygen atom of the water molecule are cis to each other. The chelate rings are all asymmetric.

Visible and ultraviolet spectra of tetraethylammonium tetrakis(β-diketonato) cerate(III) and tetrakis(β-diketonato)cerium(IV) complexes

A number of β-diketonates of cerium(III), [NEt4][CeIIIL4], and cerium(IV), [CeIVL4], have been prepared and their spectra have been recorded in the visible and u.v. regions. The spectra of the cerium(III) complexes show a group of two or three bands of moderate intensity at frequencies just below those of the strong intraligand transitions. Such bands are assigned as cerium(III)-to-ligand electron transitions or as 4f→5d transitions. For the cerium(IV) complexes a very broad absorption is found on the red side of the intraligand transitions, and is attributed to ligand-to-metal electron transfers.