Marco
Caricato
a,
Arnaud
Delforge
b,
Davide
Bonifazi
bc,
Daniele
Dondi
a,
Andrea
Mazzanti
d and
Dario
Pasini
*ae
aDepartment of Chemistry, University of Pavia, Viale Taramelli, 10, 27100, Pavia, Italy. E-mail: dario.pasini@unipv.it; Web: http://www.unipv.it/labt
bDepartment of Chemistry and Namur Research College (NARC), University of Namur (UNamur), Rue de Bruxelles 61, Namur, 5000, Belgium
cDepartment of Chemical and Pharmaceutical Sciences and INSTM UdR Trieste, University of Trieste, Piazzale Europa 1, Trieste, 34127, Italy
dDepartment of Industrial Chemistry “Toso Montanari”, School of Science, University of Bologna, V. Risorgimento 4, 40136, Bologna, Italy
eINSTM Research Unit, University of Pavia, Italy
First published on 20th January 2015
We describe the design and synthesis of a novel functionality-rich, homochiral macrocycle, possessing the overall molecular D2 symmetry, in which multivalency is introduced into the covalent framework by means of four suitably positioned pyridine moieties. The macrocycle synthesis is carried out with functionalized, enantiopure 1,1′-binaphthyl synthons as the source of chirality by means of a room temperature esterification reaction as the cyclization procedure. Upon addition of Pd2+, coordination of the pyridine moieties occurs both intra and intermolecularly, to afford chiral ordered mono and dimeric macrocycles or multimeric aggregates depending on the solvents and conditions used. The metal binding event takes place in combination with a significant macrocyclic conformational rearrangement detected by circular dichroism spectroscopy. When in combination with a third component (C60), the macrocycle-Pd2+ hybrid undergoes surface-confined nanostructuring into chiral nanofibres.
Conformationally stable macrocycles have been used with success in the realization of organic nanotubes, by means of their assembly in the third dimension by the supramolecular organization of suitable self-recognizing functionalities embedded into the cyclic skeleton. In order to form porous nanotubes, preformed covalent macrocycles do possess a number of advantages over smaller building blocks. The covalent cyclic skeleton can avoid the possibility of having interpenetrated networks, often observed in metal–organic frameworks, and can lead to a cavity of predetermined, and tunable, dimensions. Some molecular building blocks successfully adopted for this strategy include cyclic oligopeptides, macrocyclic oligophenyleneethynylenes, urea-containing macrocycles, aromatic oligoamides, calixarenes and cyclodextrins.2 Whereas early examples of cyclic oligopeptides incorporate alternating amino acid residues with opposed stereochemistries, resulting in achiral cyclic covalent molecules, more recent reports have explored similar cyclic systems with an overall net chirality.3
Several elegant examples of self-assembled helical chemical systems have been reported to date; the transmission of the chiral information often relies on “weak” molecular chirality (for example, aliphatic carbon chains with an asymmetric carbon atom) expressed far away from the assembly area (for example, π–π stacking of extended aromatics as the assembly mode).4 The introduction of a robust source of chirality into a suitable cyclic covalent skeleton can lead to innovative systems, in which helicity, and directionality, when transferred to the whole nanotube assembly, might give access to unprecedented properties on the nanoscale.5
We have recently reported the preparation of several chiral macrocycles incorporating Binol (1,1′-bi-2-naphthol) units, as a rigid, robust source of chirality induction. We have shown their applications for the chiroptical sensing of organic or ionic species.6 In this paper, we report on the design, synthesis, supramolecular and nanoscale organization of homochiral, Binol-based multivalent macrocycles using a metal-coordination strategy as the assembly mode.
(a) the use of rigid aromatic spacers joining two binaphthyl-based units, in order to define an internal, non-collapsible macrocyclic inner space, and of a minimum number of sp3 carbon atoms, which impart a higher flexibility and conformational mobility to the covalent structure with respect to sp or sp2 hybridized carbon atoms;
(b) the use of macrocyclization reactions able to generate chemical functionalities which could ensure both configurational and chemical stability to the resulting cyclic, covalent structure. Ester functionalities can ensure supramolecular “silence”, in terms of competition/interaction with other functionalities introduced within the macrocyclic framework, for assembly purposes;
(c) the coordination of the pyridine moieties to suitable PdCl2 complexes as the 3D assembly mode; this interaction, reported to form trans-coordinated complexes, has been previously used for the construction of complex supramolecular architectures, and it can ensure appropriate geometries in the assembly process.7,8
Fig. 1 illustrates graphically the concepts expressed above. The homochiral, D2 symmetrical macrocyclic skeleton (top left) contains four p-linked pyridine moieties, of which two are above (green) and two below (red) the mean plane of the macrocycle. In the presence of a suitable Pd2+ source, coordination of two pyridine units can form, in principle, different kinds of nanoscale structures: (i) closed monomers and dimers, with an overall D2 symmetry, which are feasible if the coordination can occur intramolecularly between pyridine moieties belonging to the two different binaphthyl units, facing each other, of the same macrocyclic molecule; (ii) irregular assemblies, or regular helical nanotubes, in which coordination involving the pyridine moieties occurs exclusively in an intermolecular fashion.
The synthesis of the key macrocycle is shown in Scheme 1. We have utilized commercially available, ether bridged dicarboxylic acid 2 as the rigid spacer, deemed suitable in order to define an internal, noncollapsible cavity, and previously utilized in the construction of rigid macrocycles for nanotube assembly.2f Benzylic diol (R)-1, bearing protected methoxy functionalities in the 2,2′ positions of the binaphthyl skeleton, could be cyclized with equimolar quantities of 2 to give model macrocycle (RR)-3 in fair yields, after purification by column chromatography.
Scheme 1 Synthesis of homochiral model macrocycle (RR)-3, and of homochiral multivalent macrocycle (RR)-8. |
The introduction of four pyridine functionalities within the macrocyclic framework had to be carried out convergently, since attempts to unmask the protected phenol functionalities in (RR)-3, in order to carry out postfunctionalization of the covalent structure, resulted inevitably in the degradation of the cyclic framework. The synthesis of elaborated precursor (R)-7 used our recently reported strategy6c for compound (R)-4 in excellent yields; subsequent alkylation under mildly basic conditions afforded precursor (R)-6, which could be deprotected using literature conditions to give (R)-7. The cyclization of elaborated precursor (R)-7, under the esterification conditions reported above for (R)-1, afforded macrocycle (RR)-8, after purification by column chromatography using polar eluent mixtures, in reasonable yields. In the macrocyclization reactions for the synthesis of (RR)-3 and (RR)-8, conversions of starting materials were complete; traces of higher macrocycles, and oligomeric–polymeric baseline material completed the compositions of the reaction mixtures. Precursors and macrocycles were fully characterized using NMR spectroscopy and mass spectrometric techniques. Macrocycle (RR)-8 could be stored intact for several months as a solid at 0 °C.
1H NMR studies of macrocycle (RR)-8 in different solvents showed a complex situation which was difficult to rationalize immediately. Further complications in the interpretation of the results derived from solubility/precipitation behaviour of the adducts formed by the addition of Pd2+ by changing the concentration conditions of the samples.
When macrocycle (RR)-8 was used at relatively high concentrations (1–3 mM) in d6-DMSO by the addition of increasing amounts of Pd(MeCN)2Cl2 or Pd(PhCN)2Cl2 a completely soluble adduct was generated, and no further signal changes could be detected upon addition of more than 2 equivalents of Pd2+. Fig. 2 shows the two sets of resonances for the symmetry-related CH2 groups (bottom, two double doublets for the diastereotopic protons), becoming four different sets of resonances upon reaching two equivalents of the Pd2+ source. This splitting is in agreement with the presence of a “closed dimer” structure (Fig. 1), in which the aggregate maintains a overall D2 symmetry, but the molecular fragments (red and green in the figure) are no longer equivalent through symmetry, generating different signals in the 1H NMR spectra. To further ensure that the observed 1H NMR signals belong to the “closed dimer” proposed structure, 2D-1H-DOSY NMR spectra were recorded to obtain an estimate for the size of the aggregate and compared it to the assumed structure. The measured diffusion coefficient for the free macrocycle (D = 1.25 × 10−10 m2 s−1) was found to be essentially twice of that of the adduct formed upon addition of two equivalents of Pd(PhCN)2Cl2 (D = 6.31 × 10−11 m2 s−1) (Fig. S1, ESI†). The values can be translated by the Stokes–Einstein equation9 to a hydrodynamic radius and a dimension that is essentially double with respect to that of the macrocycle, in agreement with the calculated structures by molecular modelling (vide infra).
Fig. 2 Partial 1H NMR spectra of macrocycle (RR)-8 (d6-DMSO, 3 mM, bottom) and of (RR)-8 in the presence of 2 equivalents of Pd(MeCN)2Cl2 (top). Residual solvent peaks are marked with asterisks. |
1H NMR studies were also performed in MeCN, in order to have a direct comparison with the titration behaviour monitored by UV and CD spectroscopies (vide infra). When macrocycle (RR)-8 was used at a relatively high concentration (1 mM) in MeCN, the addition of increasing amounts of Pd(MeCN)2Cl2 or Pd(PhCN)2Cl2 resulted in the formation of an insoluble precipitate. This observation suggested the possibility of an irregular aggregation. However, similar precipitation phenomena, at the same concentration, upon titration with Pd(MeCN)2Cl2, could be observed with control compound (R)-6. Since difunctional (R)-6 can only form linear aggregates, the precipitation suggested the possibility that the aggregate species formed in (RR)-8 could indeed be ordered, but not very soluble in the specific solvent. Even pyridine by itself in CH3CN formed, at millimolar concentrations, insoluble precipitates when Pd(MeCN)2Cl2 was added to the solution.
Control studies carried out with pyridine in MeCN at lower concentration levels (<10−4 M) showed that, upon addition of the Pd2+ source, the complex remained fully soluble; interestingly, and to our surprise, the displacement of the MeCN ligands on the Pd2+ coordinating center is not completely regiospecific. The formation of two different types of complexes, attributed to the cis and trans Pd(Py)2Cl2 square planar species, in a 1:3 ratio, respectively, is evident upon addition of more than 0.5 equivalent of Pd(MeCN)2Cl2 (Fig. S2†). In the case of difunctional compound (R)-6, under more diluted conditions (2.3 × 10−5 M), fully soluble adducts upon the addition of Pd2+ were obtained. The broadening of all proton resonances in the 1H NMR spectra supports strongly the formation of a coordination polymer with no further changes in the spectra observed when more than 1 equivalent of Pd2+ is added with respect to the ligand (R)-6. The observed stoichiometry at saturation (1:1 ligand vs. Pd2+) matches with the complete incorporation of the pyridine moieties (two per ligand) into the Pd2+ complexes (Fig. S3†).
In the case of macrocycle (RR)-8 (Fig. 3) at a low concentration (2.8 × 10−5 M), upon addition of the Pd2+ source, no precipitation occurred and 1H NMR spectroscopy revealed the assembly of soluble aggregates; these aggregates are in part polymeric in nature, as testified by the severe broadening of the baseline. A highly symmetrical adduct is also present, which possesses the same sets of proton resonances as the monomer macrocycle.
Fig. 3 1H NMR of (in d3-MeCN at 25 °C; top) macrocycle (RR)-8 (2.8 × 10−5 M, 500 MHz); (bottom) same with 2 equiv. of Pd(MeCN)2Cl2 added. |
We have attributed this adduct to the “closed monomer” structure (Fig. 1), since in this structure “red” and “green” molecular fragments are equivalent by symmetry operations, therefore do not generate any splitting in the NMR pattern. Together with the downfield shifts of the α-pyridyl protons, and the broadening of the β-pyridyl protons under the baseline, which could be expected upon Pd2+ coordination, substantial variations in chemical shifts could be observed for the signals attributable to the –CH2– protons, testifying the high degree of conformational rearrangement that the macrocycle has to undertake in order to form this particular structure.
MeCN as a solvent has ideal UV cutoff properties for the study of the systems presented in this paper. In fact, three distinct chromophoric units are present, and they possess characteristic UV bands; since they are joined by sp3 carbon atoms, they are not in conjugation with each other, so that the specific electronic transitions should persist in the UV spectra of the precursors and macrocycles. The major absorption band (Fig. S4†), centered around 230 nm can be attributed to the binaphthyl chromophore, with molar absorptivities (logε between 4 and 5) fully in line with other non-conjugated binaphthyl synthons.6b,c,e The band centered at 270 nm present in macrocycles (RR)-3 and (RR)-8 is assigned to the spacer chromophore unit, given the fact it is completely absent in precursor (R)-6, and also by comparison with published UV spectra of alkyl ester derivatives of 2.10 The band of the pyridine chromophores is known to be low in intensity11 and it is probably hidden by the broad band of the binaphthyl units. Circular dichroism spectroscopy of the same compounds shows the exciton couplet typical of binaphthyl moieties (Fig. S5†), corresponding to the maximum absorption band in the UV spectra. No induced CD signal could be observed in the UV bands of the other chromophores in either macrocycles (RR)-3 and (RR)-8 or the precursors.
The UV/Vis titration was complicated by the inherent absorption of the Pd2+ source (Fig. S6†) in the absorbance region of the chromophores belonging to the macrocycle (RR)-8. Upon addition of Pd(MeCN)2Cl2 to (RR)-8, at concentrations similar to those of the 1H NMR titration, small but substantial shifts in the silent absorbance region of the added Pd2+ species (310 nm), fully saturating at 2 equivalents, could be detected (Fig. 4, top).
Monitoring of the titration using CD spectroscopy was certainly more informative. An intense induced CD band appeared in correspondence with the band of the spacer chromophore unit at ca. 270 nm, and saturates upon the addition of two equivalents of Pd2+. The exciton couplet band attributable to the binaphthyl unit shows little variation in its highest energy branch at 220 nm. An intense induced CD activity could also be detected between 230 and 250 nm, and could be attributed to the chromophore band arising from the formation of the Pd2+ complex with the pyridines. This band, which is partially superimposed with the lowest energy branch of the binaphthyl couplet, and with the other band centered at 270 nm, does not saturate at 2 equivalents; a continuous shift of this band is presumably signalling a shift of the equilibrium between closed monomer/polymeric aggregates upon addition of the Pd2+ source in solution. The induced CD signal in the bands of the chromophore spacer ester and of the Pd2+ complex with the pyridine moieties indicates an overall chirality of the closed monomer/polymeric aggregates as a whole, and it stresses the high degree of conformational rearrangement occurring, upon coordination, involving all moieties of the macrocycle.
Control experiments with compound (R)-6 were carried out under identical conditions. The CD spectra revealed very little changes upon complexation, indicating how difunctional (R)-6 does not have to change its conformation in the formation of the coordination oligomeric/polymeric adduct (Fig. S7†).
Fig. 5 AFM images of (RR)-8, C60 and PdCl2(MeCN)2 at the HOPG interface. (A and B) Example of fibres. (C) A height profile measured along the white line (highlighted in black box) in (B). |
On observing the same sample after three months, we found long fibers (Fig. 6) possessing the molecular height of the single aggregates (1–1.5 nm).
Fig. 6 AFM images of (RR)-8, C60 and PdCl2(MeCN)2 visualized after a few months. Left: example of fibres. Right: a height profile measured along the colored lines. |
Control experiments of the single components and of their binary mixtures only showed amorphous materials. We also performed control experiments with difunctional compound (R)-6, again obtaining no nanostructured fibers under the same conditions as those used for macrocycle (RR)-8.
These observations are in agreement with the formation of an ordered nanostructured material, in which the nanoscale fibres are formed by single macrocyclic units piled up along a preferential dimension; the results exclude the formation of a fully crosslinked network, yet they do not support the formation of macroscopic chiral nanotubes on surfaces. Unfortunately, due to some limitations in the solubility (see above), we could not perform any studies in solution. On the other hand it is likely that the fullerene spheres are included in the macrocycle-Pd2+ coordination complexes, thus acting as templates directing the growth and the assembly of the chiral monomolecular fibres on the surface.
Initially, the trans coordination of the pyridine moieties and of the two chlorine atoms as ligands on the Pd2+ center was imposed a priori before further optimization. Even after using the preliminary PM3 screening, it appeared evident that the intramolecular positioning of two pyridine moieties belonging to two different binaphthyl units of the same macrocycle afforded a plausible and relatively stable conformer. Instead, the possible complexation of Pd2+ by two pyridines attached to the same binaphthyl unit, either in a cis or a trans complexation mode, could be thoroughly excluded. Upon optimization with DFT, two low energy conformers could be located (A and B in Fig. 7), with the form B being more stable by about 5 kcal mol−1.
The difference between the two depends on which pyridine attached to the naphthyl unit of the facing binaphthyls is involved in the intramolecular trans complexation on the Pd2+ center. In form A, the two pyridines involved are the one above and the one below the mean plane of the macrocycle (red and green in Fig. 1), whereas in form B they are both above the mean plane of the macrocycle (both green according to Fig. 1). The molecules show similar dihedral angles for the binaphthyl units (79 and 84° for A, 86 and 82° for B) and identical bond angles for the spacer oxygen atom (PhOPh angles of 122° in all cases). The overall dimensions of the minimized structures are similar in both cases (2.6 × 1.7 nm maximum dimensions for conformer A; 2.4 × 1.3 nm maximum dimensions for conformer B). The main difference is that in form B, the two pyridine moieties not involved in the complexation are predisposed for further joining of another similar unit. In fact, conformer B can easily close to give a stable dimer (the “closed dimer” form in Fig. 1), which is shown in Fig. 8. The modelling of “closed dimer” and of conformer B was then performed independently; we did not observe any significant changes in the geometry of the intramolecularly complexed macrocycle in either monomer or dimer, as to testify that the macrocyclic structure does not have to undergo a high degree of conformational rearrangement to close to a dimeric structure.
On the other hand, it is likely that the conformer A, with two pyridine moieties pointing away from the macrocyclic structure in opposite directions, is the one involved in the formation of the nanostructured aggregates observed in solution and on surfaces.
In order to rationalize the “closed monomer” structure, which was observed under some of the conditions reported before, calculations were performed on macrocycle (RR)-8 by imposing a cis geometry for the intramolecular Pd2+ complex stabilized by two pyridine moieties of the facing binaphthyls. We have verified that this structure is plausible, both in terms of stability and symmetry, with the proposed structure shown in Fig. 1. The lowest energy conformer in this case is shown in Fig. 9.
Footnote |
† Electronic supplementary information (ESI) available: Additional UV, CD and NMR spectra, and copies of NMR and mass spectra for all newly synthesized compounds. See DOI: 10.1039/c4ob02643h |
This journal is © The Royal Society of Chemistry 2015 |