Lorenzo Millia,
Enrico Marchi*a,
Nicola Castelluccia,
Maria Teresa Indellib,
Margherita Venturiac,
Paola Ceroniac and
Claudia Tomasini*a
aDipartimento di Chimica “G. Ciamician”, Università di Bologna, Via F. Selmi 2, 40126 Bologna, Italy. E-mail: claudia.tomasini@unibo.it; enrico.marchi@unibo.it
bDipartimento di Scienze Chimiche e Farmaceutiche, Università di Ferrara, Via Fossato di Mortara 17, 44121 Ferrara, Italy
cCentro Interuniversitario per la Conversione dell'Energia Solare (SolarChem), Italy
First published on 8th January 2015
We have designed and prepared three pseudopeptide foldamers, called dyads 1, 2 and 3, equipped with a donor and an acceptor unit to promote intramolecular electron transfer after light excitation. All the three dyads contain the same donor and acceptor, which are a derivative of 1,5-dihydroxynaphthalene and a derivative of pyromellitic diimide, respectively. The donor and acceptor units are separated by hybrid foldamers of different length in order to vary both their distance and relative orientation. Specifically, one, two or three L-Ala-D-Oxd (Ala = alanine, Oxd = 4-carboxy-5-methyl-oxazolidin-2-one) units are contained in dyads 1, 2, and 3, respectively. Dyad 1 folds in a bent conformation in which the donor and acceptor units lie one close to the other, while dyads 2 and 3 preferentially assume an extended conformation. In all the three dyads both the donor and acceptor emissions are efficiently quenched via intramolecular electron transfer, as suggested by photophysical and electrochemical investigations. Because of its bent conformation dyad 1 exhibits a charge-transfer (CT) band at 410 nm in CH2Cl2 solution and a photoinduced electron transfer that occurs more efficiently than in dyads 2 and 3. Upon dissolving dyad 1 in DMSO, a competitive solvent for hydrogen bonds that establish in the pseudopeptide linker, the CT band disappears and the efficiency of electron transfer slightly decreases, in agreement with an unfolded conformation in which donor and acceptor units are no longer in close contact.
Over the last 50 years several donor and acceptor chromophores have been examined in the context of their capability to form charge-transfer (CT) complexes.6 In the frame of these investigations, it has also been evidenced that the linker plays a key role to put in communication the two chromophores. In principle, a lot of different linkers could be used for this purpose, providing pathways through peptide bonds, aromatic side chains, weak noncovalent hydrophobic interactions, hydrogen-bonding networks associated with helices and sheets and/or other secondary structural features that change the electronic structure and induce low-energy pathways across polypeptides.7 Among the peptide bridging groups studied, the oligoproline building blocks were used as a key model for systematic study of the distance dependence of the electron transfer process.8 The advantage of the oligoprolines over other naturally occurring amino acids and peptides is the predictability of their secondary structure, which imparts significant rigidity upon the spatial separation between the donor and acceptor.9
In the last few years, the design and synthesis of oligomers based on proline units, both in the presence and absence of stabilizing hydrogen bonds, have been extensively pursued. Interesting new molecules capable of folding into defined secondary structures may be prepared by replacing the proline moieties with pseudoproline (ΨPro) units.10
Simplified artificial systems based on backbones designed to fold in secondary structures are called “foldamers”, and they have recently received considerable attention because they hold promises for addressing chemical, physico-chemical and biological problems and represent a new frontier in research.11 We have extensively studied the conformational behavior of foldamers containing a pseudoproline scaffold as 4-carboxy-5-methyl-oxazolidin-2-one (Oxd)12 On acylation of this pseudoproline unit, imides are obtained: the two carbonyls lie apart from one another and form the peptide bond in a trans conformation.13 We have also reported hybrid foldamers, where the Oxd moiety is alternated with an α- or a β-amino acid.14 The relative configuration of the Oxd and the alternated amino acid is very important, as the L-Ala-D-Oxd series tends to form β-bend ribbon spirals, while the L-Ala-L-Oxd series does not.
In this paper, we report the synthesis, the conformational characterization and the photophysical investigation of a series of hybrid oligomers, called dyads 1, 2 and 3 (Fig. 1). They contain a derivative of pyromellitic diimide as electron acceptor group and a derivative of 1,5-dihydroxynaphthalene as the electron donor one. These two moieties are linked by one, two, or three L-Ala-D-Oxd units in dyads 1, 2 and 3.
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Fig. 1 Formulas of the investigated dyads 1, 2 and 3 and the acceptor and compounds 4 and 5 taken as models of the acceptor and donor units, respectively. |
The aim of this work is to check if the photophysical properties, and in particular the interaction between the donor and acceptor units, are affected by the different bridge and by the resulting conformation of the foldamers.
The acceptor group, a pyromellitic diimide, has been prepared in one step as white powder by reaction of pyromellitic dianhydride with dodecylamine and glycine in refluxing DMF in 28% yield.15 Besides 6, that was used for the dyads preparation, the corresponding methyl ester 4 (Fig. 1) was synthesized as acceptor model for the photophysical analysis, by reaction of 6 with SOCl2 in CH3OH (Scheme 1).
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Scheme 1 Reagents and conditions: (i) Gly (1.0 equiv.), dodecylamine (1.0 equiv.), DMF, 120 °C, 6 h; (ii) SOCl2 (excess), MeOH, r.t., 24 h. |
The donor 8 was prepared in two steps starting from the commercially available 1,5-dihydroxynaphthalene (Scheme 2). After reaction with potassium carbonate, potassium iodide and n-heptyl bromide in acetone, a mixture of the desired 5-(heptyloxy)naphthalen-1-ol 7 and 1,5-bis(heptyloxy)naphthalene 5 was prepared. After purification, 7 and 5 were obtained in 37% and 30% yield respectively. While 7 was used for the dyad preparation, 5 was used as donor model for the photophysical analysis. Finally 7 was coupled with Boc-L-Ala in the presence of DCC and DMAP to give the final product 8 in 55% yield.
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Scheme 2 Reagents and conditions: (i) 1-bromoheptane (1.0 equiv.), K2CO3 (2.1 equiv.), KI (1.0 equiv.), acetone, reflux, 10 h; (ii) DCC (1.1 equiv.), DMAP (0.1 equiv.), DCM, r.t., 24 h. |
As mentioned before, the donor and the acceptor units were linked together by the spacers, that are oligomers of the Boc-(L-Ala-D-Oxd)n-OH series (n = 1, 2, 3), whose synthesis was previously reported.16 The preparation of dyads 1, 2 and 3 was obtained by two steps, by standard peptide coupling reactions with the acceptor group and the donor group (Scheme 3).
NH stretching bands of dyads 1, 2 and 3 are shown in Fig. 2: the spectrum of 1 clearly shows the presence of two bands at 3420 and 3340 cm−1, that account for an hydrogen-bonded and a non-hydrogen-bonded amide NH group. The stretching band at 3340 cm−1 becomes weaker for 2 and totally disappears in the case of 3. This finding suggests that a folded conformation is strongly favoured in the case of the shortest dyad 1, whereas it occurs only partially in dyad 2 and it does not take place at all in dyad 3.
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Fig. 2 N–H stretching regions of the FT-IR absorption spectra in pure CH2Cl2 at room temperature for 3 mM concentration of dyads 1 (black line), 2 (red line) and 3 (green line). |
A further confirmation of the preferred bent conformation assumed by 1 was obtained by analyzing the chemical shifts of the pyromellitic diimide and 1,5-dihydronaphthalene hydrogens. These chemical shifts for dyads 1, 2 and 3 together with those found for the model compound 4 and compound 8 are reported in Table 1.
Solvent | δH1 (ppm) | δH2 (ppm) | δH3 (ppm) | δH4 (ppm) | δH5 (ppm) | δH6 (ppm) | δH7 (ppm) | |
---|---|---|---|---|---|---|---|---|
1 | CDCl3 | 8.02 | 7.26 | 7.13 | 6.74 | 7.22 | 7.02 | 7.85 |
2 | CDCl3 | 8.18 | 7.36 | 7.20 | 6.79 | 7.36 | 7.32 | 8.25 |
3 | CDCl3 | 8.17 | 7.39 | 7.18 | 6.79 | 7.36 | 7.31 | 8.27 |
4 | CDCl3 | — | — | — | — | — | — | 8.33 |
8 | CDCl3 | 8.21 | 7.44 | 7.23 | 6.83 | 7.38 | 7.42 | — |
1 | DMSO, d6 | 8.02 | 7.46 | 7.20 | 6.99 | 7.38 | 7.32 | 8.15 |
4 | DMSO, d6 | 8.03 | 7.47 | 7.22 | 6.97 | 7.38 | 7.44 | — |
8 | DMSO, d6 | — | — | — | — | — | — | 8.22 |
We can notice that H7 resonates as a singlet for both hydrogens at 8.33 ppm in the spectrum of 4 (Fig. 3). In dyads 1, 2 and 3 there is no skeleton modification that could be responsible for the variation of this chemical shift. In fact, both 2 and 3 spectra show a singlet at 8.25 and 8.27 ppm respectively. In contrast, in the dyad 1 spectrum, the chemical shift of the pyromellitic diimide hydrogens resonates at 7.85 ppm, suggesting that these hydrogens are shielded by an aromatic ring (Fig. 3). The same effect was observed for the chemical shifts of the 1,5-dihydronaphtalene hydrogens (compound 8), that are all shielded only in the case of dyad 1. This outcome suggests that all the aromatic hydrogens of dyad 1 suffer from the shielding effect of a nearby aromatic ring.
Interestingly, when the 1H NMR spectra of compounds 1, 4 and 8 are registered in DMSO, d6, the chemical shifts variations are negligible as Δδ ranges from 0 to 0.12 ppm, while in CDCl3 it ranges between 0.09 and 0.47 ppm (Table 1 and ESI† for details). Thus the bent conformation of 1 is favoured by CHCl3, that is a structure supporting solvent and is disfavoured by DMSO, that is a competitive solvent for N–H⋯OC bonds (see below).18
ROESY experiments performed on dyads 1 and 2 (as a model of the unfolded dyads), in CDCl3 using a mixing time of 0.400 s, proved this hypothesis.
Besides the trivial couplings, in the ROESY spectrum of 1 in CDCl3, several cross peaks accounting for the interactions between the pyromellitic diimide and 1,5-dihydronaphthalene hydrogens and NH are visible and are highlighted (see ESI† for more details). In contrast, in the ROESY spectrum of 2 these signals are totally absent (see ESI† for more details). This finding is in agreement with a preferred bent conformation of 1, that favours the proximity between the donor and the acceptor groups in a range of about 4 Å. The preferred conformation of dyad 1, together with all the cross peaks registered in the ROESY spectrum, is summarized in Fig. 4.
Absorption | Emissionb | ηqd | ||||
---|---|---|---|---|---|---|
λ (nm) | ε (M−1 cm−1) | λ (nm) | ϕ | τ (ns)c | ||
a Shoulder of the absorption band.b For the three dyads data are reported only for the residual emission of the donor subunit (λex = 280 nm). No sensitized or residual emission of the acceptor subunit is observed.c The fitting equation is I = A1![]() ![]() |
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1 | 300 | 10![]() |
330 | 0.002 | 0.12 (0.73) | 0.99 |
308a | 9300 | 5.30 (0.02) | ||||
410 | 150 | |||||
2 | 299 | 10![]() |
330 | 0.013 | 0.31 (0.41) | 0.95 |
308a | 9600 | 5.30 (0.03) | ||||
3 | 300 | 11![]() |
330 | 0.027 | 0.52 (0.31) | 0.91 |
308a | 10![]() |
5.30 (0.03) | ||||
4 | 309 | 1950 | 447 | 0.003 | 9.45 | — |
319 | 2000 | |||||
5 | 298 | 9950 | 330 | 0.25 | 6.30 | — |
313 | 8200 | |||||
327 | 6100 |
In addition, the spectrum of 1 is characterized by an unstructured, large and weak band centered at 410 nm (inset of Fig. 5) that is not present in the spectra of dyads 2 and 3. This band can be assigned to a CT transition between donor and acceptor units (see below), as previously reported for similar donor–acceptor components.20 The presence of this CT band only in 1 is in line with the previously reported results showing that only for the shortest dyad the donor and acceptor units undergo a noticeable interaction because of their close proximity. This band is not sensitive to concentration (the molar absorption coefficient does not change in the range 3.7 × 10−7 to 3.7 × 10−4), thus excluding intermolecular interactions, but it is sensitive to the solvent nature. In fact, the CT band disappears upon dissolution of dyad 1 in DMSO (inset of Fig. 5), a competitive solvent that promote the unfolding of the pseudopeptide (see above),18 a result evidencing that the supramolecular structure of the pseudopeptide foldamers can be easily affected.
From the emission spectra obtained by excitation of isoabsorbing CH2Cl2 solutions of 1, 2, 3 and 5 at 286 nm (Fig. 6, left) we can estimate the quenching efficiency ηq of the luminescent excited state of the donor unit in the dyads, after correction for the amount of light directly absorbed by the acceptor (Table 2, see ESI† for more details).
The quenching efficiency is higher than 90% in all cases and is decreasing from 1 to 3 in agreement with a longer distance between the donor and the acceptor units. For dyad 1 and 2 in DMSO solution (3 it is not soluble in this solvent) we observe, as expected, a stronger decrease of the quenching efficiency for dyad 1 (95%) than for dyad 2 (93%). These results are in accordance with the absence of the CT band in the absorption spectrum of 1 in DMSO. The lifetimes of the donor residual emission for the three dyads in CH2Cl2 solution are reported in Table 2. They are biexponential and characterized by a major short component (less than a ns) and a minor long component (ca. 5 ns) lifetime. The decay of the shorter lifetime is assigned to the donor molecules linked in the dyads, while the longer one is due to a small amount of free donor impurities present in solution.‡
The quenching efficiencies obtained comparing the corrected emission intensity are the same (within the experimental error) of those estimated by the analysis of the short component lifetime of the luminescent excited state of the donor in the dyads with respect to the one of 5 (Table 2 and ESI† for more details). It is important to underline that, exciting the dyads at 286 nm, we are unable to see any emission of the acceptor unit.
By excitation of isoabsorbing CH2Cl2 solutions of the dyads at 320 nm (where the 30% of the light is absorbed by the acceptor subunit), the emission spectra (Fig. 6, right) are characterized only by a very weak tail due to the residual emission of the directly excited donor unit. These emissions are completely different from the one obtained exciting at 320 nm an isoabsorbing solution of the acceptor model 4 (Fig. 6, black dashed-dotted line), demonstrating that in these systems also the luminescent excited state of the acceptor subunit is highly quenched.
On the basis of the redox potentials of the donor and the acceptor model compounds (see ESI†),§ the energy of the charge transfer (CT) state, in which the donor is oxidized (Ep.a. = +1.23 V vs. SCE) and the acceptor is reduced (E1/2 = −0.83 V vs. SCE), is lower (ca. 1.5 eV) than the energy of the excited state both of the donor and acceptor units. A schematic energy level diagram is reported in Fig. 7. The presence of this low CT state suggests that the quenching mechanism of both the donor and the acceptor excited state is via electron transfer.
In order to get a deeper insight into the electron transfer mechanism, ultrafast spectroscopic experiments in CH2Cl2 solution were performed by using 266 nm as excitation wavelength (see ESI†). No transient spectral changes with distinctive features of the formation of the charge separated product were observed in the 1–1000 ps time scale. We attribute this result to kinetic reasons: the charge recombination process to the ground state is faster than the photoinduced charge separation and, as a consequence, the charge separated product does not accumulate.
IR and NMR analyses clearly evidence that in CH2Cl2 and in CDCl3 solution dyad 1 folds in a bent conformation in which the donor and acceptor units lie in close proximity, while dyads 2 and 3 lie in a extended conformation.
The photophysical properties of the dyads in CH2Cl2 solution strongly support this conformational characterization. Indeed, the absorption spectrum of dyad 1 shows a weak and large band at 410 nm assigned to a charge transfer transition that is not present in the spectra of dyads 2 and 3 in agreement with the fact that the donor and the acceptor are in close proximity only in the shortest dyad. Furthermore, in all the three dyads both the donor and acceptor emissions are efficiently quenched most likely via intramolecular electron transfer that, because of its bent conformation, occurs more efficiently in dyad 1 than in dyads 2 and 3. The degree of interaction between the donor and acceptor units in dyad 1 can also be modulated by changing the folding of the oligopeptide bridge. Dissolving 1 in a competitive solvent like DMSO the bridge is unfolded (as pointed out by NMR experiments and by the disappearing of the CT band) bringing the donor and acceptor units at a longer distance.
To better investigate this remarkable outcome, further work is under progress in our laboratory to design and prepare new compounds with the same spacer of dyad 1, but carrying a wide plethora of acceptor and donor units.
Footnotes |
† Electronic supplementary information (ESI) available: Synthetic details, IR, NMR and ROESY spectra, quenching efficiency calculations and electrochemical details. See DOI: 10.1039/c4ra13978j |
‡ The light emitted by this component accounts for ca. 60% in the lifetime fittings, but considering its very high emission quantum yield it is possible to estimate that donor free molecule are present in concentration less than 10%. The longer lifetime is slightly different from the one reported for the donor model compound 5 likely because of the different substituents. |
§ The electrochemical investigation of the dyads was precluded by the limited amount of sample available. |
This journal is © The Royal Society of Chemistry 2015 |