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Nucleobase appended viologens: Building blocks for new optoelectronic materials
Optical Materials 42 (2015) 262–269
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Nucleobase appended viologens: Building blocks for new optoelectronic materials Marius Ciobanu a, Simona Asaftei b,⇑ a b
Department of Organic Materials Chemistry, Institute of Chemistry of New Materials, University of Osnabrück, Barbarastr. 7, 49076 Osnabrück, Germany Faculty of Management, Culture and Technology, University of Applied Sciences Osnabrueck, Kaiserstr. 10c, D-49809 Lingen (Ems), Germany
a r t i c l e
i n f o
Article history: Received 6 May 2014 Received in revised form 15 December 2014 Accepted 17 December 2014 Available online 18 February 2015 Keywords: 4,40 -Bipyridinium Thymine Adenine Self-assembly Hydrogen bonding
a b s t r a c t We describe here the fabrication, characterization and possible applications of a new type of optical material – consisting of 4,40 -bipyridinium core (‘‘viologen’’) and nucleobases i.e. adenine and/or thymine made by H-bonding. The viologen–nucleobase derivatives were used to construct supramolecular structures in a ‘‘biomimetic way’’ with complementary oligonucleotides (ssDNA) and peptide nucleic acids (ssPNA) as templates. The new nanostructured materials are expected to exhibit enhanced optical and optoelectronic properties with application in the field of supramolecular electronics. Such viologen derivatives could be significant in the design of new 2D and 3D materials with potentially application in optoelectronics, molecular electronics or sensoric. Ó 2015 Elsevier B.V. All rights reserved.
1. Introduction The molecules with multiple functionalities are promising building blocks for construction of functional materials with enhanced properties. This is because the combination of two or more distinct functions may have a cumulative effect on the overall properties and features of the corresponding material. Particular attention has been directed toward the synthesis of compounds with two functionalities consisting in a core responsible for physico-chemical properties (i.e. electrochemical, optical, etc.) and nucleotide bases as capping groups capable of molecular recognition [1–10]. A major motivation of designing such compounds lies in the ability of nucleobases to direct the self-assembly process of functional molecules which may result in a modulation of physico-chemical properties of the corresponding materials. Optical materials obtained by highly ordered assembly of p-stacked distyrylbenzenes and oligoadenines as template were described by the group of Wong [1]. Well-defined nanofibrous structure with lengths of several hundred nanometers was self-assembled by oligoadenines (dA20), and thymine-appended distyrylbenzene through binary complementary AAT hydrogen bonding and p–p stacking interaction. Numerous coordination polymers based on modified 4,40 -bipyridine, such as 4,40 -bipyridine oxide which
⇑ Corresponding author. E-mail address: [email protected] (S. Asaftei). http://dx.doi.org/10.1016/j.optmat.2014.12.044 0925-3467/Ó 2015 Elsevier B.V. All rights reserved.
exhibit 2D sheet and 3D motif formed by hydrogen bonding and p–p interaction have been well documented [2]. In this work we aimed to develop new optical/optoelectronic materials consist of a redox units with well-known electrochemical properties, and biologically activity. The building blocks molecules containing of redox active 4,40 -bipyridinium core so called ‘‘viologen’’ with are capping by two (1) and three (4) thymine units, adenine (2) and thymine/adenine (3), respectively. The combination is unusually and offer two molecular functionalities: viologen and nucleobases. The 4,40 -bipyridinium unit, known as a good electron acceptor, used in electrochemical processes and the nucleobases might act as electron donors, capable of fast electron-transfer reactions. The acceptor and the donor tails are electronically isolated trough a polymethylene spacer will lead to a separation of the molecular orbitals HOMO (located on the acceptor tail) and LUMO (located on the donor tail) which is of great interest for the field of molecular electronics. On the other hand, the nucleobase are capable of hydrogen-bonding with complementary biological target to lead to construction of new functional 2D and 3D materials. The donor–acceptor relationship between the viologen and nucleobase and the electrochemical properties with regard on the optical and redox properties was especially addressed. Depending on the molecular structure, if 4,40 -bipyridinium core is capping with a pyrimidine, a purine, or purine/pyrimidine unit, significantly different characteristics in optical and electrochemical behavior was observed. The viologen–nucleobase derivatives 1–4 were used to construct
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supramolecular structures in a ‘‘biomimetic way’’ with complementary oligonucleotides (ssDNA) and peptide nucleic acids (ssPNA) as templates. The viologen derivatives appended by nucleobases have been proved to be excellent building blocks candidates for such purpose. Such viologen derivatives could be significant in the design of new 2D and 3D materials with potentially application in optoelectronics, molecular electronics or sensor. 2. Material and methods 2.1. Materials All chemicals were purchased from Merck (D-Hohenbrunn), Sigma–Aldrich and Fluka. Solvents were of laboratory grade. Elemental analyses: VarioMICRO cube. UV Spectra: 8453 UV–Vis Spectrophotometer (Agilent, Germany) kmax in nm (e in M1 cm1). NMR Spectra: Bruker AMX-500 spectrometer; 1H: 500.13 MHz, 13 C: 125.7 MHz; chemical shifts d are given in ppm relative to the solvent signal peaks as internal standard for 1H and 13C NMR. 2.2. Electrochemistry and spectroelectrochemistry DMF and NaClO4 (puriss., electrochemical grade) were purchased from Sigma–Aldrich and Acros Organics for cyclic voltammetry and spectroelectrochemical studies. CVs were measured under Ar with the potentiostat PGSTAT 302N from AUTOLAB controlled by a PC running under GPES from Windows, version 4.9 (ECO Chemie B.V.); a glassy carbon electrode (GCE) from Metrohm (Germany) with an electrochemical active surface area of A = 0.031 cm2 was used for CV. The working electrode surface was polished with Al2O3 before the measurement. The reference electrode was Ag/AgCl (3 M KCl in water) and the counter electrode was a Pt wire. The cell used for SEC–UV–VIS measurements of compounds 1–3 in solution was an H-Type spectroelectrochemical bulk electrolysis cell [13]. The reference was an Ag/AgCl electrode immersed in an electrolyte vessel filled with LiCl (2 M in ethanol), separated from the cell by a glass frit and the counter electrode was a Pt-foil. The working electrode was 0.039 g of graphitized carbon felt GFA-5 of approximately 0.021 m2 BET area from SGL carbon, the electrochemically active area of which is not known. Absorbance changes were measured in conjunction with an Agilent 8453 Diode Array Spectrophotometer. 2.3. Temperature-absorption dependence and CD characterization Tm experiments of the mixtures of 4,40 -bipyridinium-thymine derivatives 1, 4–7 with oligonucleotides (dAn) respectively analogue peptide nucleic acid A10-PNA in phosphate buffer solution (see general preparation procedure section) were monitored with a Cary 100 UV–Vis Spectrophotometer. The measurements were consist in monitoring the absorbance at 260 nm while the sample was heated from 20 to 80 °C with 1 °C/min ramp temperature after 5 min of equilibration time. CD spectra were recorded at 20 °C with a J-600 Spectropolarimeter (Jasco, Japan). 3. Experimental 3.1. Mixture preparation of 4,40 -bipyridinium-thymine derivatives with oligonucleotides or analogue peptide nucleic acids Corresponding volumes of aqueous stock solutions of oligonucleotide (dAn) or peptide nucleic acid A10-PNA and respectively 4,40 -bipyridinium-thymine derivative were mixed in a phosphate buffer (pH = 7) to afford an equimolar ratio of thymine/adenine. The solution volume was adjusted to a final concentration of
263
20 lM thymine, respectively adenine units. Resulted mixture was heated up to 80 °C for 5 min and cooled down slowly to room temperature. The mixture solutions were then stored at 4 °C prior optical characterization. 3.2. 1,10 -Bis[3-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)propyl]-4-(pyridin-4-yl)pyridinium dibromide (1) 1-(3-Bromopropyl)-5-methyl-3H-pyrimidine-2,4(1H,3H)-dione (1.756 g, 7.1 mmol) and 4,40 -bipyridine (0.24 g, 1.54 mmol) were dissolved in dry DMF (60 mL) and stirred at 80 °C for 4 days. Resulted light-yellow precipitate was filtered, washed with DMF (20 mL), Et2O (20 mL) and dry in ultra-high vacuum at 45 °C to afford 1 as bromide salt (0.76 g, 1.16 mmol, 76%). 1H NMR (500 MHz, D2O, 30 °C): d = 9.26 (d, J = 6.62 Hz, 4H), 8.66 (d, J = 6.30 Hz, 4H), 7.60 (s, 2H), 4.93 (t, J = 7.25 Hz, 4H), 4.05 (t, J = 6.62 Hz, 4H), 2.65 (quin, J = 6.70 Hz, 4H), 1.96 ppm (s, 6H); 13C NMR (125 MHz, D2O, 30 °C): d = 166.87(s), 152.31(s), 150.31(s), 145.76(d), 142.49(d), 127.16(d), 111.47(s), 59.43(t), 45.25(t), 29.53(t), 11.33 ppm (q); elemental analysis calcd (%) for 1 as PF 6 salt C26H30F12N6O4P2 (780.48): C 40.0, H: 3.87, N 10.77; found C 39.69, H 3.60, N 10.71. 3.3. 1,10 -Bis[2-(6-amino-9H-purin-9-yl)ethyl]-4-(pyridin-4yl)pyridinium dibromide (2) 1-[2-(6-Amino-9H-purin-9-yl)ethyl]-4-(pyridin-4-yl)pyridinium monobromide (0.382 g, 0.96 mmol) and 9-(2-bromoethyl)-9H-purin-6-amine (0.6 g, 2.48 mmol) were dissolved in distilled water (30 mL) and stirred at 80 °C for 17 days. In the 10th and 14th day after reaction start, a new quantity of 9-(2-bromoethyl)-9H-purin-6-amine was added (0.2 g, respectively 0.12 g). After 17 days, reaction mixture was cooled down to 21 °C and subsequently, acetone (80 mL) was slowly added. Resulted precipitate was separated by filtration, washed with acetone (10 mL) and dry under reduced pressure to afford the product 2 (0.523 g, 0.82 mmol, 85%). 1H NMR (250 MHz, DMSO-d6, 30 °C): d = 9.19 (d, J = 6.91 Hz, 4H), 8.63 (d, J = 6.91 Hz, 4H), 8.11 (s, 2H), 7.78 (s, 2H), 7.26 (br. s., 4H), 5.14 (t, J = 5.30 Hz, 4H), 4.85 (t, J = 4.10 Hz, 4H); 13C NMR (125 MHz, D2O, 30 °C): d = 155.82(s), 152.75(d), 150.69(s), 149.19(s), 146.21(d), 142.02(d), 127.34(d), 118.19(s), 61.52(t), 44.09(t); elemental analysis calcd (%) for 2 as PF 6 salt C24H24F12N12P2 + 0.8 H2O (770.46 + 14.4): C 37.41, H 3.14, N 21.82; found: C 36.73, H 3.29, N 21.41. 3.4. 1-[2-(6-Amino-9H-purin-9-yl)ethyl]-10 -[3-(5-methyl-2,4-dioxo3,4-dihydropyrimid-in-1(2H)-yl)propyl]-4-(pyridin-4-yl)pyridinium dihexafluorophosphate (3) 1-[2-(6-amino-9H-purin-9-yl)ethyl]-4-(pyridin-4-yl)pyridinium monohexafluorophosphate (0.45 g, 0.97 mmol) and 1-(3-bromopropyl)-5-methylpyrimidine-2,4(1H,3H)-dione (0.72 g, 2.19 mmol) were disolved in dry DMF (20 mL) and stirred at 80 °C for 70 h. Resulted precipitate was filtered, washed with DMF (5 mL) and acetone (20 mL). After drying in vacuo, the resulted solid was dissolved in water (20 mL) and treated with aqueous solution of NH4PF6 (4 ml, 10 wt%). The resulted precipitate was separated by filtration, washed with water (5 mL) and dry in vacuo to obtained product 3 as a white solid yield 281 mg (0.281 g, 0.44 mmol, 45%). 1 H NMR (250 MHz, CD3CN, 30 °C): d = 9.78 (br. s, 1H), 8.94 (d, J = 6.91 Hz, 2H), 8.67 (d, J = 6.91 Hz, 2H), 8.34 (d, J = 6.91 Hz, 2H), 8.23 (d, J = 6.59 Hz, 2H), 7.94 (s, 1H), 7.79 (s, 1H), 7.23 (s, 1H), 6.22 (br. s., 2H), 5.07 (t, J = 5.70 Hz, 2H), 4.80 (t, J = 5.00 Hz, 2H), 4.67 (t, J = 7.06 Hz, 2H), 3.79 (t, J = 6.12 Hz, 2H), 2.40 (quin, J = 1.00 Hz, 2H), 1.85 (s, 3H); 13C NMR (125 MHz, CD3CN, 30 °C): d = 165.78(s), 157.43(s), 154.05(d), 152.90(s), 151.96(s), 151.70(s),
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151.20(s), 147.69(d), 147.37(d), 142.32(d), 142.08(d), 128.65(d), 128.54(d), 120.26(s), 111.93(s), 63.02(t), 60.93(t), 45.43(t), 45.40(t), 31.86(t), 12.73(q); elemental analysis calcd (%) for 3 as PF 6 salt C25H27F12N9O2P2 + 0.1 H2O (775.48 + 1.8): C 38.72, H 3.51, N 16.26; found: C 38.63, H 3.53, N 16.22. 4. Results and discussion 4.1. Synthesis The synthesis of compounds 1–3 starts with the construction of 1-(3-bromopropyl)-5-methyl-3H-pyrimidine-2,4(1H,3H)-dione and 9-(2-bromoethyl)-9H-purin-6-amine respectively, which were obtained by alkylation of thymine or adenine with an excess of corresponding alkyl dihalide in DMF according to the literature (Scheme 1, route I and II) [14–21]. In the case of the synthesis of 1-(3-bromopropyl)-5methylpyrimidine-2,4(1H,3H)-dione, conversion of the thymine to bis-(O-silylated) analogue derivative was necessary, in order to protect the carbonyl groups prior the alkylation reaction (route I, step i). The symmetrical disubstituted 4,4-bipyridinium derivative 1 was prepared by one pot dialkylation of 4,40 -bipyridine using 4.6 fold excess of 1-(3-bromopropyl)-5-methyl-3H-pyrimidine2,4(1H,3H)-dione in DMF (route I, step iii). The synthesis of compound 2, which involves dialkylation of 4,40 -bipyridine with excess of 9-(2-bromoethyl)-9H-purin-6amine, failed in solvents like DMF or acetonitrile. The low solubility of the adenylic substrate in such polar aprotic solvents and the formation of bromide anion during the alkylation reaction determines the precipitation of the mono-alkylated 4,40 -bipyridine product before the second quaternization takes place. The best yield (85%) and no mixture of mono- and disubstituted products were obtained in water at 80 °C after 17 days (route II, step vi). The supplementary addition of 9-(2-bromoethyl)-9H-purin-6-amine was required during the reaction because the alkylation substrate is consumed partially in a secondary reaction with water. In this manner, compound 3 was prepared (route II, step vii and viii). Starting from 4,40 -bipyridine, the alkylation reaction was
performed first with an excess of 9-(2-bromoethyl)-9H-purin-6amine in nitrobenzene to yields compound P2. In the second reaction step, the compound P2 as PF 6 salt was treated with 3 fold excess of 1-(3-bromopropyl)-5-methylpyrimidine-2,4(1H,3H)dione in DMF to yield the corresponding asymmetrically 1,10 -disubstituted 4,40 -bipyridinium compound (3) (see Fig. 1). The structure and integrity of the novel compounds 1–3 were confirmed by 1H and 13C NMR (see supporting information) and elemental analysis. 4.2. Optical characterization Dicationic derivatives 1–3 were investigated by mean of UV–Vis spectroscopy as halogenide salts in aqueous solution or as PF 6 salts in DMF. The optical characterization in reduced state was performed in a three-electrode system electrochemical cell, using Ag/AgCl as reference electrode and NaClO4/DMF as supporting electrolyte at 24 °C. The optical data derived from the corresponding UV–Vis spectra of 1–3 in dicationic state (V2+) and radicalcationic state (V+) respectively, are depicted in Table 1. The compounds 1–3 in dicationic state absorb light in UV range due to the overlapped electronic transitions of chromophoric units (thymine, adenine and 4,40 -bipyridinium) (see kmax1 in Table 1). The broad absorption band seen in the visible domain (around 400 nm) for all three compounds it is assigned to a charge transfer interaction (CT) of nucleobases with 4,40 -bipyridinium core (Fig. 2). The extinction coefficient of CT band (eCT) is direct proportional with the association constant (Kass) of CT complexation and increases in the order 2 < 3 < 1. This could be assigned to the higher flexibility of the propylene spacer (1) compared to ethylene (2) which permits to the donor moiety to fold and stack with the acceptor core in a parallel face-to-face conformation. Park et al. [22,23] have also claimed the influence of the polymethylene linkage on the CT association between 4,40 -bipyridinium and aromatic donors in a similar molecular design. The possible ion pair charge-transfer (IPCT) between viologen core and the counter anion it is excluded [24]. The PF 6 used as counter anion in this study, is known as a non-coordinative anion.
Scheme 1. Synthetic pathway of compounds 1–3. Route I: (i) HMDS and Me3SiCl (cat.), 21 h, reflux, 95%, (ii) 3 equiv. of 1,3-dibromopropane, DMF, 24 h, 80 °C, 34%, (iii) 4,40 bipyridine, DMF, 4 days, 80 °C, 76% (1); (iv) 4,40 -bipyridine, nitrobenzene, 48 h, 110 °C, 83%; Route II: (v) 1,2-dibromoethane, K2CO3 in DMF, 48 h, r.t., 61%, (vi) 4,40 -bipyridine, H2O, 17 days, 80 °C, 85% (2); (vii) 4,40 -bipyridine, nitrobenzene, 48 h, 110 °C, 92%; (viii) P2 as PF 6 salt with 2-fold excess of 1-(3-bromopropyl)-5-methylpyridine2,4(1H,3H)dione, DMF, 70 h, 80 °C, 45% (3).
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Fig. 1. Kinetic evolution of P1, respectively P2 in nitrobenzene (110 °C).
Table 1 Optical properties of compounds 1–3a. Compound
Oxidized state (V2+) kmax1(e)
1 2 3
b
268 (46.1) 260 (45.5) 263(44.4)
Reduced state (V+) c
kmax2(e)
kmax3(e)d
kmax4(e)d
404 (1.21) 412 (0.74) 405 (1.1)
401 (44.40) 401 (37.67) 401 (38.50)
607(14.69) 605 (13.43) 606 (13.08)
a Maximum wavelength (k) in nm and related extinction coefficient (e) in parenthesis expressed as 103 L mol1 cm1. b Determined from 0.05 mM solution in water. c Determined from 0.1 mM solution in DMF. d Determined from 0.1 mM solution in NaClO4/DMF (0.1 M).
Fig. 3. UV–Vis absorption spectra of compound 1 in the reduced state, 0.1 mM concentration in 0.1 M NaClO4/DMF. Inset: plot of normalized absorbance at 600 nm versus potential of compounds 1–3.
to the radical cation species (V+) (inflection point of the sinusoidal curves) represents the half-wave potential of the first reduction step (E1/2) and their values are in fully agreement with those obtained from electrochemical measurements that will be presented in the next section. 4.3. Electrochemical characterization Compounds 1, 2 and 3 were characterized by cyclic voltammetry in 0.1 M NaClO4/DMF electrolyte solution at the surface of a glassy carbon electrode at 24 °C. The cyclic voltammograms in Fig. 4 represent the typical electrochemical reduction of 4,40 -bipyridinium units from the dication state (V2+) to radical cation (V+) of corresponding to derivatives 1, 2 and 3, respectively. The ratio between cathodic and anodic current peaks (Ipc/Ipa) was calculated after baseline correction of the corresponding cyclic voltammograms and satisfies the condition of reversibility (Ipc/Ipa = 1) for each reduction steps. The electrochemical parameters of the compounds 1, 2 and respectively 3 are presented in Table 2. First step reduction of compounds 1–3 is a diffusion-controlled process in the scan rate range from 0.1 to 1 V s1 (see the linear plot of Ipc1 versus the square root of the scan rate in Supporting Information). The diffusion coefficients of derivatives 1–3 of the dicationic species in DMF (Table 2) were calculated from a derivative form of Randles-Ševcík Eq. (1):
D ¼ ðB=2:69 105 z3=2 A cÞ
2
ð1Þ
Fig. 2. VIS absorption spectra of compounds 1–3 (0.1 mM) in DMF. Inset: concentration dependency with molar extinction coefficient at 412 nm.
The molar extinction coefficient of the CT band increases with the decrease of concentration (inset, Fig. 2). This trend shows that the CT interaction between 4,40 -bipyridinium unit and the nucleobases is disrupted by the increasing of the intrinsic ionic strength. The effect of ionic strength was extensively discussed by Monk for a wide variety of CT complexes of the viologens [25]. Compounds 1–3 have in the reduced state (V+) the typical blue color of viologens with maximum wavelengths at 401 nm and respectively 605 nm (Fig. 3). The behavior is similarly with 1,10 dibenzyl-4,4-bipyridinium (DBV2+). The radical-cation formation at 600 nm as a function of potential is showing in Fig. 3 inset. The potential value for which half of the species V2+ are reduced
Fig. 4. Cyclic voltammograms of compound 1 (continuous line), 2 (dotted line) and 3 (dashed line) in 0.1 M NaClO4/DMF at 0.1 V/s scan rate versus Ag/AgCl.
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Table 2 Electrochemical parameters for the compounds 1–3 from cyclic voltammetrya. v
Epc1b
Epa1
Eo1c
DE1d
Epc2
Epa2
Eo2
DE 2
1
6
3.3 10
0.1 0.3 0.6 1
391 393 393 393
330 325 320 317
360 359 357 355
61 68 73 76
781 784 789 791
718 715 720 715
750 750 755 753
63 69 69 76
2
3.1 106
0.1 0.3 0.6 1
342 342 344 342
273 269 269 266
308 306 307 304
69 73 75 76
715 723 725 732
649 649 649 659
682 686 687 696
66 74 76 73
3
3.4 106
0.1 0.3 0.6 1
366 366 369 366
298 298 295 288
332 332 332 344
68 68 74 78
752 757 764 771
681 684 686 684
717 721 725 727
71 73 78 87
Compound
a b c d
D
All potential parameters are expressed in mV, the diffusion coefficients (D) in cm2 s1 and the scan rate (v) in V s1. Epc1, Epa1, Epc2 and Epa2 represent the corresponding half-wave potentials from CVs. Eo1 and Eo2 represent the calculated formal potentials. DE1 and DE2 represent the separation potential.
where D is the diffusion coefficient; B is the slope of the linear regression of the peak current (Ipc1) versus the square root of the scan rate; T is the temperature (298 K); A is the area of the surface of the electrode (0.031 cm2); z is the number of electron transferred (z = 1) and c is the concentration of the analyte in electrolyte solution (5 104 M). The compounds 1–3 have diffusion coefficients with relatively closed values and similar to well-known analogue 1,10 -dimethyl4,4-bipyridinium (paraquat), suggesting no self-association of dicationic species in DMF. The compound 1–3 were reduced at much more positive potential compared to well-known analogue 1,10 -dimethyl-4,40 -bipyridinium (E01 = 380 mV versus Ag/AgCl) measured in the similar experimental conditions [26]. The low positive potentials observed in the case of compounds 1–3 is attributed to the electronic effects of the substituents 9-(2-ethylene)adenine and/or 1-(3-propylene)thymine attached covalently to the nitrogen atoms. The formal potential values E01 and E02, corresponding to each electron transfer step, are more negative (approx. 60 mV) in the case of compound 1 compared with compound 2, while the formal potentials of compound 3 are situated between the values recorded for the compounds 1 and 2 (Table 2). The observed difference in the formal potential is explained by the charge transfer interaction between nucleobases as charge donors and 4,40 -bipyridinium core as charge acceptor. The dicationic state of the compound 1 was stabilized to a higher extent by charge transfer interaction with peripheral thymine group and therefore was reduced at a much negative potential than compound 2. The results from the electrochemical characterization are highly supported by the optical data which also suggests a higher charge transfer association constant in the case of compound 1 compared with compound 2, while compound 3 has an intermediary value. In the term of optical characteristics, the LUMO energy level of compounds 1–3, which is located on the acceptor moiety (4,40 bipyridinium) was affected by the charge transfer interaction with the pendant nucleobases. From electrochemical data was possible to calculate the exact energy of these molecular orbitals applying a calculation procedure reported in the literature [27]. We found a value of 4.11 eV for compound 1, 4.16 eV for compound 2 and 4.13 eV for compound 3, respectively. 4.4. Templated self-assemblies of viologen–thymine derivatives with homoadenylic oligonucleotides and analogue ssPNA The self-assembly approach of thymine-appended 4,4-bipyridinium derivatives with oligonucleotide dAn by adenine–thymine
hydrogen bonding was used to create highly ordered aggregates in solution exhibiting enhanced optoelectronic properties. In a first experiment two types of viologen–thymine derivatives were assembled in the presence of 40-mer adenylic oligonucleotide (dA40): type A (rode-like molecule 1) and type B (y-shaped molecule 4) [28] accordingly with the Scheme 2. The interaction of viologen–thymine derivatives 1 and 4, respectively with oligonucleotide dA40 was studied in a phosphate solution buffer (pH = 7). The components, i.e. viologen–thymine derivative (1 or 4) and oligonucleotide dA40, were mixed in an equimolar ratio of thymine/adenine units. The resulted mixtures were characterized by temperature-absorbance dependence experiments (Tm) and circular dichroism (CD) spectroscopy (Fig. 5). After mixing the components, a fraction of oligonucleotide dA40 precipitated as a result of competitive electrostatic interaction between polycationic scaffold of viologen–thymine derivatives and negatively charged riboso-phosphate backbone of dA40. The CD spectra (Fig. 5c and d) of the supernatant mixtures of 1:dA40 and G0:dA40, respectively showed that oligonucleotide dA40 coexists in solution with viologen–thymine compounds bellow a critical concentration and is expected to form hydrogen-bonded aggregates. The temperature-absorbance dependence experiments performed on supernatant mixtures 1:dA40 and G0:dA40 respectively, revealed a sharp increase of the nucleobase absorbance at 37 °C (Fig. 5a and b). The hyperchromic effect at 260 nm over the temperature is typical for the cooperative hydrogen bond breaking of thymine–adenine base pair in the dsA-T [1]. This results suggest that the unprecipitated dA40, remained in the supernatant solution, was hydrogen bonded with the complementary thymine appended viologen derivatives 1 and 4, respectively. Notably, the compound 4 showed a sharper hyperchromic effect compared to 1 in interaction with dA40 demonstrating a higher cooperativity of hydrogen bonding in the corresponding supramolecular aggregate. The possible self-assembled supramolecular models of compounds 1 and 4, respectively by hydrogen bonding with dA40 are presented in Scheme 2. In these models, the oligonucleotide dA40 plays the role of a template that directs the formation of an ordered fibrillar nanostructure. The two models are inspired by the plenty of examples in the literature referring to the ability of single stranded DNA to direct the formation of hydrogen-bonded supramolecular structures with fibrillar architectures [5–9,11,12]. The corresponding supramolecular aggregates are stabilized mainly by hydrogen bonding between the complementary nucleobases adenine and thymine units but other supramolecular forces, such as p–p staking or hydrophobic interactions between adjacent nucleobases
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267
Scheme 2. Self-assembly models of compounds type A: 1 and type B: 4 with ssDNA(dA40) as template by hydrogen bonding.
Fig. 5. Temperature-absorbance dependence experiment of compound 1 (a) and 4 (b) in the presence of dA40 in phosphate buffer (pH = 7). CD spectra dA40 in the absence (continue lines, c and d) and in the presence of compound 1 (c) and 4 (d) in phosphate buffer (dashed lines).
may also contribute energetically to the stabilization of the supramolecular assemblies, in a similar way as seen in the double stranded DNA (dsDNA). Further investigations in the solid state, i.e. crystallographic characterization, are in progress to confirm the proposed models.
In a second experiment, we studied the influence of the number of positive charges per molecule of 4,40 -bipyridinium-thymine derivative and the length of oligonucleotide in the same conditions as mentioned above. The compounds 1, 4 and a series of viologen-based dendrimers, with thymine units on the periphery
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Fig. 6. Temperature-absorbance dependence experiment of the aqueous solution mixtures of compound 4–7 with complementary adenylic PNA 10-mer (A10-PNA) in equimolar ratio T/A.
and polycationic scaffold [29] carrying 18 (5), 42 (6) and 90 (7) charges per molecule were used for the interaction with oligonucleotides dAn with different lengths (n = 20, 40, 80, 140). Except the compound 1 and 4 which produced a partial precipitation of oligonucleotide, the dendritic compounds (5–7) precipitated practically the entire amount of oligonucleotide dA40 (see supporting information). The amount of precipitated dAn increases with the increase of the number of positive charges per molecule of 4,40 -bipyridinium-thymine derivative and the length of the oligonucleotides dAn. In a third experiment, the behavior of derivatives 4–7 in the presence of analogue oligoadenylic PNA 10-mer was studied. The peptide nucleic acid (PNA) template have neutral backbone and no precipitation was observed. Tm measurements of aqueous mixtures of 4, 5, 6 and 7, respectively with PNA oligomer (A10-PNA) showed the same sharp hyperchromic transition at 260 nm with the temperature, typically for T@A hydrogen bonds breaking in double helix DNA (Fig. 6). The interaction mode between viologen–thymine derivatives and ssPNA-A10 was exclusively by hydrogen bonding. The results showed that the self-assembly process by hydrogen bonding is favored by the increase of the number of thymine units per viologen–thymine derivative, but becomes unfavorable with the increase of the number of positive charges due to the electrostatic interaction. Incorporation of viologen–nucleobase derivatives into a highly ordered supramolecular matrix by making use of hydrogen bonding ability of nucleobases to bind complementary templates is a promising approach to create new materials with enhanced optoelectronic properties. 5. Conclusions Nucleobase-appended viologens 1–3 were synthesized mainly by coupling the regioselective alkylated nucleobases to 4,40 -bipyridine unit by nucleophilic substitution reactions. They were characterized in the term of optical and electrochemical properties. A charge transfer interaction between the viologen unit as acceptor and nucleobases as donor was demonstrated by UV–Vis spectroscopy. The CT complexation has been influenced by the flexibility of the polymethylene linkage between nucleobase and viologen and by the nature of corresponding donor units (i.e. purinic or pyrimidinic base). The donor–acceptor relationship was found to affect optical characteristics of the viologen core in dicationic state and to play a significant role in the modulation of the necessary
energy required for the electron transfer (ET). Nevertheless, the electronic state or radical cation (V+) was not affected by the CT complexation upon electrochemical reduction since the compounds 1–3 had the typical blue color of ‘‘unconjugated’’ viologens such as 1,10 -dibenzyl-4,40 -bipyridinium derivative (DBV+). Thymine-appended viologens 1 and 4, differing in shape and number of nucleobase capping groups, were incorporated into a welldefined supramolecular matrix as optical/redox additives using the ability of thymine base to recognize and bind by hydrogen bonding complementary templates like oligonucleotides. The self-assembly process driven by thymine–adenine molecular recognition in aqueous solution has been demonstrated by optical methods (temperature-absorbance experiments and CD spectroscopy). Notably, the polycationic viologen–thymine derivatives were found to interact electrostatically with oligonucleotides beyond a critical concentration leading to ssDNA precipitation. Systematic studies were revealed that electrostatic interaction is strongly influenced by the oligonucleotide length and by the number of positive charges per viologen–thymine derivative. To avoid electrostatic interaction, which is undesirable for construction of hydrogen bonded self-assembled aggregates in solution, the oligonucleotides were replaced by peptide nucleic acids (PNA) with neutral backbone. The investigations in the presence of PNA template were extended to a series of four macromolecular viologen–thymine derivatives with dendritic architecture (4–7) and the optical characterization revealed that the self-assembly process was exclusively by hydrogen bonding. Construction of supramolecular templated aggregates with well-defined structure and size is of great importance for designing new materials with tuned optical or optoelectronic properties. The viologen derivatives appended by nucleobases have been proved to be excellent building blocks candidates for such purpose. Acknowledgements We gratefully thank our co-worker Ana-Maria Lepadatu for synthesis of the viologen-based dendrimers 4–7 used in the interaction studies with ssDNA and ssPNA. Appendix A. Supplementary material Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.optmat.2014.12. 044. References [1] W. Yang, P.F. Xia, M.S. Wong, Org. Lett. 12 (2010) 4018–4021. [2] B.Q. Ma, S. Gao, H.L. Sun, G.X. Xu, Cryst. Eng. Commun. 35 (2001) 1–5. [3] M. Möller, S. Asaftei, D. Corr, M. Ryan, L. Walder, Adv. Mater. 16 (2004) 1558– 1562. [4] H.J. Kim, J.K. Seo, Y.J. Kim, H.K. Jeong, G.I. Lim, Y.S. Choi, W.I. Lee, Sol. Energy Mater. Sol. C 93 (2009) 2108–2112. [5] H. Santa-Nokki, J. Kallioinen, J. Korppi-Tommola, Photochem. Photobiol. Sci. 6 (2007) 63–66. [6] Y. Kim, G.G. Malliaras, C.K. Ober, E. Kim, J. Nanosci. Nanotechnol. 10 (2010) 6869–6873. [7] Z. Sharrett, S. Gamsey, L. Hirayama, B. Vilozny, J.T. Suri, R.A. Wessling, B. Singaram, Org. Biomol. Chem. 7 (2009) 1461–1470. [8] P. Bhowmik, H. Han, I. Nedeltchev, J. Cebe, Mol. Cryst. Liq. Cryst. 419 (2004) 27–46. [9] K. Tanabe, T. Yasuda, M. Yoshio, T. Kato, Org. Lett. 9 (2007) 4271–4274. [10] S. Asaftei, M. Ciobanu, A.M. Lepadatu, E. Song, U. Beginn, J. Mater. Chem. 22 (2012) 14426–14437. [11] L.R. Rieth, R.F. Eaton, G.W. Coates, Angew. Chem. Int. Ed. 40 (2001) 2153–2156. [12] L. Brunsveld, B.J.B. Folmer, E.W. Meijer, R.P. Sijbesma, Chem. Rev. 101 (2001) 4071–4098. [13] B. Steiger, L. Walder, Helv. Chim. Acta 75 (1992) 90–108. [14] N. Baret, J.P. Dulcere, J. Rodriguez, J.M. Pons, R. Faure, Eur. J. Org. Chem. 8 (2000) 1507–1516.
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Optical Materials journal homepage: www.elsevier.com/locate/optmat
Nucleobase appended viologens: Building blocks for new optoelectronic materials Marius Ciobanu a, Simona Asaftei b,⇑ a b
Department of Organic Materials Chemistry, Institute of Chemistry of New Materials, University of Osnabrück, Barbarastr. 7, 49076 Osnabrück, Germany Faculty of Management, Culture and Technology, University of Applied Sciences Osnabrueck, Kaiserstr. 10c, D-49809 Lingen (Ems), Germany
a r t i c l e
i n f o
Article history: Received 6 May 2014 Received in revised form 15 December 2014 Accepted 17 December 2014 Available online 18 February 2015 Keywords: 4,40 -Bipyridinium Thymine Adenine Self-assembly Hydrogen bonding
a b s t r a c t We describe here the fabrication, characterization and possible applications of a new type of optical material – consisting of 4,40 -bipyridinium core (‘‘viologen’’) and nucleobases i.e. adenine and/or thymine made by H-bonding. The viologen–nucleobase derivatives were used to construct supramolecular structures in a ‘‘biomimetic way’’ with complementary oligonucleotides (ssDNA) and peptide nucleic acids (ssPNA) as templates. The new nanostructured materials are expected to exhibit enhanced optical and optoelectronic properties with application in the field of supramolecular electronics. Such viologen derivatives could be significant in the design of new 2D and 3D materials with potentially application in optoelectronics, molecular electronics or sensoric. Ó 2015 Elsevier B.V. All rights reserved.
1. Introduction The molecules with multiple functionalities are promising building blocks for construction of functional materials with enhanced properties. This is because the combination of two or more distinct functions may have a cumulative effect on the overall properties and features of the corresponding material. Particular attention has been directed toward the synthesis of compounds with two functionalities consisting in a core responsible for physico-chemical properties (i.e. electrochemical, optical, etc.) and nucleotide bases as capping groups capable of molecular recognition [1–10]. A major motivation of designing such compounds lies in the ability of nucleobases to direct the self-assembly process of functional molecules which may result in a modulation of physico-chemical properties of the corresponding materials. Optical materials obtained by highly ordered assembly of p-stacked distyrylbenzenes and oligoadenines as template were described by the group of Wong [1]. Well-defined nanofibrous structure with lengths of several hundred nanometers was self-assembled by oligoadenines (dA20), and thymine-appended distyrylbenzene through binary complementary AAT hydrogen bonding and p–p stacking interaction. Numerous coordination polymers based on modified 4,40 -bipyridine, such as 4,40 -bipyridine oxide which
⇑ Corresponding author. E-mail address: [email protected] (S. Asaftei). http://dx.doi.org/10.1016/j.optmat.2014.12.044 0925-3467/Ó 2015 Elsevier B.V. All rights reserved.
exhibit 2D sheet and 3D motif formed by hydrogen bonding and p–p interaction have been well documented [2]. In this work we aimed to develop new optical/optoelectronic materials consist of a redox units with well-known electrochemical properties, and biologically activity. The building blocks molecules containing of redox active 4,40 -bipyridinium core so called ‘‘viologen’’ with are capping by two (1) and three (4) thymine units, adenine (2) and thymine/adenine (3), respectively. The combination is unusually and offer two molecular functionalities: viologen and nucleobases. The 4,40 -bipyridinium unit, known as a good electron acceptor, used in electrochemical processes and the nucleobases might act as electron donors, capable of fast electron-transfer reactions. The acceptor and the donor tails are electronically isolated trough a polymethylene spacer will lead to a separation of the molecular orbitals HOMO (located on the acceptor tail) and LUMO (located on the donor tail) which is of great interest for the field of molecular electronics. On the other hand, the nucleobase are capable of hydrogen-bonding with complementary biological target to lead to construction of new functional 2D and 3D materials. The donor–acceptor relationship between the viologen and nucleobase and the electrochemical properties with regard on the optical and redox properties was especially addressed. Depending on the molecular structure, if 4,40 -bipyridinium core is capping with a pyrimidine, a purine, or purine/pyrimidine unit, significantly different characteristics in optical and electrochemical behavior was observed. The viologen–nucleobase derivatives 1–4 were used to construct
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supramolecular structures in a ‘‘biomimetic way’’ with complementary oligonucleotides (ssDNA) and peptide nucleic acids (ssPNA) as templates. The viologen derivatives appended by nucleobases have been proved to be excellent building blocks candidates for such purpose. Such viologen derivatives could be significant in the design of new 2D and 3D materials with potentially application in optoelectronics, molecular electronics or sensor. 2. Material and methods 2.1. Materials All chemicals were purchased from Merck (D-Hohenbrunn), Sigma–Aldrich and Fluka. Solvents were of laboratory grade. Elemental analyses: VarioMICRO cube. UV Spectra: 8453 UV–Vis Spectrophotometer (Agilent, Germany) kmax in nm (e in M1 cm1). NMR Spectra: Bruker AMX-500 spectrometer; 1H: 500.13 MHz, 13 C: 125.7 MHz; chemical shifts d are given in ppm relative to the solvent signal peaks as internal standard for 1H and 13C NMR. 2.2. Electrochemistry and spectroelectrochemistry DMF and NaClO4 (puriss., electrochemical grade) were purchased from Sigma–Aldrich and Acros Organics for cyclic voltammetry and spectroelectrochemical studies. CVs were measured under Ar with the potentiostat PGSTAT 302N from AUTOLAB controlled by a PC running under GPES from Windows, version 4.9 (ECO Chemie B.V.); a glassy carbon electrode (GCE) from Metrohm (Germany) with an electrochemical active surface area of A = 0.031 cm2 was used for CV. The working electrode surface was polished with Al2O3 before the measurement. The reference electrode was Ag/AgCl (3 M KCl in water) and the counter electrode was a Pt wire. The cell used for SEC–UV–VIS measurements of compounds 1–3 in solution was an H-Type spectroelectrochemical bulk electrolysis cell [13]. The reference was an Ag/AgCl electrode immersed in an electrolyte vessel filled with LiCl (2 M in ethanol), separated from the cell by a glass frit and the counter electrode was a Pt-foil. The working electrode was 0.039 g of graphitized carbon felt GFA-5 of approximately 0.021 m2 BET area from SGL carbon, the electrochemically active area of which is not known. Absorbance changes were measured in conjunction with an Agilent 8453 Diode Array Spectrophotometer. 2.3. Temperature-absorption dependence and CD characterization Tm experiments of the mixtures of 4,40 -bipyridinium-thymine derivatives 1, 4–7 with oligonucleotides (dAn) respectively analogue peptide nucleic acid A10-PNA in phosphate buffer solution (see general preparation procedure section) were monitored with a Cary 100 UV–Vis Spectrophotometer. The measurements were consist in monitoring the absorbance at 260 nm while the sample was heated from 20 to 80 °C with 1 °C/min ramp temperature after 5 min of equilibration time. CD spectra were recorded at 20 °C with a J-600 Spectropolarimeter (Jasco, Japan). 3. Experimental 3.1. Mixture preparation of 4,40 -bipyridinium-thymine derivatives with oligonucleotides or analogue peptide nucleic acids Corresponding volumes of aqueous stock solutions of oligonucleotide (dAn) or peptide nucleic acid A10-PNA and respectively 4,40 -bipyridinium-thymine derivative were mixed in a phosphate buffer (pH = 7) to afford an equimolar ratio of thymine/adenine. The solution volume was adjusted to a final concentration of
263
20 lM thymine, respectively adenine units. Resulted mixture was heated up to 80 °C for 5 min and cooled down slowly to room temperature. The mixture solutions were then stored at 4 °C prior optical characterization. 3.2. 1,10 -Bis[3-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)propyl]-4-(pyridin-4-yl)pyridinium dibromide (1) 1-(3-Bromopropyl)-5-methyl-3H-pyrimidine-2,4(1H,3H)-dione (1.756 g, 7.1 mmol) and 4,40 -bipyridine (0.24 g, 1.54 mmol) were dissolved in dry DMF (60 mL) and stirred at 80 °C for 4 days. Resulted light-yellow precipitate was filtered, washed with DMF (20 mL), Et2O (20 mL) and dry in ultra-high vacuum at 45 °C to afford 1 as bromide salt (0.76 g, 1.16 mmol, 76%). 1H NMR (500 MHz, D2O, 30 °C): d = 9.26 (d, J = 6.62 Hz, 4H), 8.66 (d, J = 6.30 Hz, 4H), 7.60 (s, 2H), 4.93 (t, J = 7.25 Hz, 4H), 4.05 (t, J = 6.62 Hz, 4H), 2.65 (quin, J = 6.70 Hz, 4H), 1.96 ppm (s, 6H); 13C NMR (125 MHz, D2O, 30 °C): d = 166.87(s), 152.31(s), 150.31(s), 145.76(d), 142.49(d), 127.16(d), 111.47(s), 59.43(t), 45.25(t), 29.53(t), 11.33 ppm (q); elemental analysis calcd (%) for 1 as PF 6 salt C26H30F12N6O4P2 (780.48): C 40.0, H: 3.87, N 10.77; found C 39.69, H 3.60, N 10.71. 3.3. 1,10 -Bis[2-(6-amino-9H-purin-9-yl)ethyl]-4-(pyridin-4yl)pyridinium dibromide (2) 1-[2-(6-Amino-9H-purin-9-yl)ethyl]-4-(pyridin-4-yl)pyridinium monobromide (0.382 g, 0.96 mmol) and 9-(2-bromoethyl)-9H-purin-6-amine (0.6 g, 2.48 mmol) were dissolved in distilled water (30 mL) and stirred at 80 °C for 17 days. In the 10th and 14th day after reaction start, a new quantity of 9-(2-bromoethyl)-9H-purin-6-amine was added (0.2 g, respectively 0.12 g). After 17 days, reaction mixture was cooled down to 21 °C and subsequently, acetone (80 mL) was slowly added. Resulted precipitate was separated by filtration, washed with acetone (10 mL) and dry under reduced pressure to afford the product 2 (0.523 g, 0.82 mmol, 85%). 1H NMR (250 MHz, DMSO-d6, 30 °C): d = 9.19 (d, J = 6.91 Hz, 4H), 8.63 (d, J = 6.91 Hz, 4H), 8.11 (s, 2H), 7.78 (s, 2H), 7.26 (br. s., 4H), 5.14 (t, J = 5.30 Hz, 4H), 4.85 (t, J = 4.10 Hz, 4H); 13C NMR (125 MHz, D2O, 30 °C): d = 155.82(s), 152.75(d), 150.69(s), 149.19(s), 146.21(d), 142.02(d), 127.34(d), 118.19(s), 61.52(t), 44.09(t); elemental analysis calcd (%) for 2 as PF 6 salt C24H24F12N12P2 + 0.8 H2O (770.46 + 14.4): C 37.41, H 3.14, N 21.82; found: C 36.73, H 3.29, N 21.41. 3.4. 1-[2-(6-Amino-9H-purin-9-yl)ethyl]-10 -[3-(5-methyl-2,4-dioxo3,4-dihydropyrimid-in-1(2H)-yl)propyl]-4-(pyridin-4-yl)pyridinium dihexafluorophosphate (3) 1-[2-(6-amino-9H-purin-9-yl)ethyl]-4-(pyridin-4-yl)pyridinium monohexafluorophosphate (0.45 g, 0.97 mmol) and 1-(3-bromopropyl)-5-methylpyrimidine-2,4(1H,3H)-dione (0.72 g, 2.19 mmol) were disolved in dry DMF (20 mL) and stirred at 80 °C for 70 h. Resulted precipitate was filtered, washed with DMF (5 mL) and acetone (20 mL). After drying in vacuo, the resulted solid was dissolved in water (20 mL) and treated with aqueous solution of NH4PF6 (4 ml, 10 wt%). The resulted precipitate was separated by filtration, washed with water (5 mL) and dry in vacuo to obtained product 3 as a white solid yield 281 mg (0.281 g, 0.44 mmol, 45%). 1 H NMR (250 MHz, CD3CN, 30 °C): d = 9.78 (br. s, 1H), 8.94 (d, J = 6.91 Hz, 2H), 8.67 (d, J = 6.91 Hz, 2H), 8.34 (d, J = 6.91 Hz, 2H), 8.23 (d, J = 6.59 Hz, 2H), 7.94 (s, 1H), 7.79 (s, 1H), 7.23 (s, 1H), 6.22 (br. s., 2H), 5.07 (t, J = 5.70 Hz, 2H), 4.80 (t, J = 5.00 Hz, 2H), 4.67 (t, J = 7.06 Hz, 2H), 3.79 (t, J = 6.12 Hz, 2H), 2.40 (quin, J = 1.00 Hz, 2H), 1.85 (s, 3H); 13C NMR (125 MHz, CD3CN, 30 °C): d = 165.78(s), 157.43(s), 154.05(d), 152.90(s), 151.96(s), 151.70(s),
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151.20(s), 147.69(d), 147.37(d), 142.32(d), 142.08(d), 128.65(d), 128.54(d), 120.26(s), 111.93(s), 63.02(t), 60.93(t), 45.43(t), 45.40(t), 31.86(t), 12.73(q); elemental analysis calcd (%) for 3 as PF 6 salt C25H27F12N9O2P2 + 0.1 H2O (775.48 + 1.8): C 38.72, H 3.51, N 16.26; found: C 38.63, H 3.53, N 16.22. 4. Results and discussion 4.1. Synthesis The synthesis of compounds 1–3 starts with the construction of 1-(3-bromopropyl)-5-methyl-3H-pyrimidine-2,4(1H,3H)-dione and 9-(2-bromoethyl)-9H-purin-6-amine respectively, which were obtained by alkylation of thymine or adenine with an excess of corresponding alkyl dihalide in DMF according to the literature (Scheme 1, route I and II) [14–21]. In the case of the synthesis of 1-(3-bromopropyl)-5methylpyrimidine-2,4(1H,3H)-dione, conversion of the thymine to bis-(O-silylated) analogue derivative was necessary, in order to protect the carbonyl groups prior the alkylation reaction (route I, step i). The symmetrical disubstituted 4,4-bipyridinium derivative 1 was prepared by one pot dialkylation of 4,40 -bipyridine using 4.6 fold excess of 1-(3-bromopropyl)-5-methyl-3H-pyrimidine2,4(1H,3H)-dione in DMF (route I, step iii). The synthesis of compound 2, which involves dialkylation of 4,40 -bipyridine with excess of 9-(2-bromoethyl)-9H-purin-6amine, failed in solvents like DMF or acetonitrile. The low solubility of the adenylic substrate in such polar aprotic solvents and the formation of bromide anion during the alkylation reaction determines the precipitation of the mono-alkylated 4,40 -bipyridine product before the second quaternization takes place. The best yield (85%) and no mixture of mono- and disubstituted products were obtained in water at 80 °C after 17 days (route II, step vi). The supplementary addition of 9-(2-bromoethyl)-9H-purin-6-amine was required during the reaction because the alkylation substrate is consumed partially in a secondary reaction with water. In this manner, compound 3 was prepared (route II, step vii and viii). Starting from 4,40 -bipyridine, the alkylation reaction was
performed first with an excess of 9-(2-bromoethyl)-9H-purin-6amine in nitrobenzene to yields compound P2. In the second reaction step, the compound P2 as PF 6 salt was treated with 3 fold excess of 1-(3-bromopropyl)-5-methylpyrimidine-2,4(1H,3H)dione in DMF to yield the corresponding asymmetrically 1,10 -disubstituted 4,40 -bipyridinium compound (3) (see Fig. 1). The structure and integrity of the novel compounds 1–3 were confirmed by 1H and 13C NMR (see supporting information) and elemental analysis. 4.2. Optical characterization Dicationic derivatives 1–3 were investigated by mean of UV–Vis spectroscopy as halogenide salts in aqueous solution or as PF 6 salts in DMF. The optical characterization in reduced state was performed in a three-electrode system electrochemical cell, using Ag/AgCl as reference electrode and NaClO4/DMF as supporting electrolyte at 24 °C. The optical data derived from the corresponding UV–Vis spectra of 1–3 in dicationic state (V2+) and radicalcationic state (V+) respectively, are depicted in Table 1. The compounds 1–3 in dicationic state absorb light in UV range due to the overlapped electronic transitions of chromophoric units (thymine, adenine and 4,40 -bipyridinium) (see kmax1 in Table 1). The broad absorption band seen in the visible domain (around 400 nm) for all three compounds it is assigned to a charge transfer interaction (CT) of nucleobases with 4,40 -bipyridinium core (Fig. 2). The extinction coefficient of CT band (eCT) is direct proportional with the association constant (Kass) of CT complexation and increases in the order 2 < 3 < 1. This could be assigned to the higher flexibility of the propylene spacer (1) compared to ethylene (2) which permits to the donor moiety to fold and stack with the acceptor core in a parallel face-to-face conformation. Park et al. [22,23] have also claimed the influence of the polymethylene linkage on the CT association between 4,40 -bipyridinium and aromatic donors in a similar molecular design. The possible ion pair charge-transfer (IPCT) between viologen core and the counter anion it is excluded [24]. The PF 6 used as counter anion in this study, is known as a non-coordinative anion.
Scheme 1. Synthetic pathway of compounds 1–3. Route I: (i) HMDS and Me3SiCl (cat.), 21 h, reflux, 95%, (ii) 3 equiv. of 1,3-dibromopropane, DMF, 24 h, 80 °C, 34%, (iii) 4,40 bipyridine, DMF, 4 days, 80 °C, 76% (1); (iv) 4,40 -bipyridine, nitrobenzene, 48 h, 110 °C, 83%; Route II: (v) 1,2-dibromoethane, K2CO3 in DMF, 48 h, r.t., 61%, (vi) 4,40 -bipyridine, H2O, 17 days, 80 °C, 85% (2); (vii) 4,40 -bipyridine, nitrobenzene, 48 h, 110 °C, 92%; (viii) P2 as PF 6 salt with 2-fold excess of 1-(3-bromopropyl)-5-methylpyridine2,4(1H,3H)dione, DMF, 70 h, 80 °C, 45% (3).
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Fig. 1. Kinetic evolution of P1, respectively P2 in nitrobenzene (110 °C).
Table 1 Optical properties of compounds 1–3a. Compound
Oxidized state (V2+) kmax1(e)
1 2 3
b
268 (46.1) 260 (45.5) 263(44.4)
Reduced state (V+) c
kmax2(e)
kmax3(e)d
kmax4(e)d
404 (1.21) 412 (0.74) 405 (1.1)
401 (44.40) 401 (37.67) 401 (38.50)
607(14.69) 605 (13.43) 606 (13.08)
a Maximum wavelength (k) in nm and related extinction coefficient (e) in parenthesis expressed as 103 L mol1 cm1. b Determined from 0.05 mM solution in water. c Determined from 0.1 mM solution in DMF. d Determined from 0.1 mM solution in NaClO4/DMF (0.1 M).
Fig. 3. UV–Vis absorption spectra of compound 1 in the reduced state, 0.1 mM concentration in 0.1 M NaClO4/DMF. Inset: plot of normalized absorbance at 600 nm versus potential of compounds 1–3.
to the radical cation species (V+) (inflection point of the sinusoidal curves) represents the half-wave potential of the first reduction step (E1/2) and their values are in fully agreement with those obtained from electrochemical measurements that will be presented in the next section. 4.3. Electrochemical characterization Compounds 1, 2 and 3 were characterized by cyclic voltammetry in 0.1 M NaClO4/DMF electrolyte solution at the surface of a glassy carbon electrode at 24 °C. The cyclic voltammograms in Fig. 4 represent the typical electrochemical reduction of 4,40 -bipyridinium units from the dication state (V2+) to radical cation (V+) of corresponding to derivatives 1, 2 and 3, respectively. The ratio between cathodic and anodic current peaks (Ipc/Ipa) was calculated after baseline correction of the corresponding cyclic voltammograms and satisfies the condition of reversibility (Ipc/Ipa = 1) for each reduction steps. The electrochemical parameters of the compounds 1, 2 and respectively 3 are presented in Table 2. First step reduction of compounds 1–3 is a diffusion-controlled process in the scan rate range from 0.1 to 1 V s1 (see the linear plot of Ipc1 versus the square root of the scan rate in Supporting Information). The diffusion coefficients of derivatives 1–3 of the dicationic species in DMF (Table 2) were calculated from a derivative form of Randles-Ševcík Eq. (1):
D ¼ ðB=2:69 105 z3=2 A cÞ
2
ð1Þ
Fig. 2. VIS absorption spectra of compounds 1–3 (0.1 mM) in DMF. Inset: concentration dependency with molar extinction coefficient at 412 nm.
The molar extinction coefficient of the CT band increases with the decrease of concentration (inset, Fig. 2). This trend shows that the CT interaction between 4,40 -bipyridinium unit and the nucleobases is disrupted by the increasing of the intrinsic ionic strength. The effect of ionic strength was extensively discussed by Monk for a wide variety of CT complexes of the viologens [25]. Compounds 1–3 have in the reduced state (V+) the typical blue color of viologens with maximum wavelengths at 401 nm and respectively 605 nm (Fig. 3). The behavior is similarly with 1,10 dibenzyl-4,4-bipyridinium (DBV2+). The radical-cation formation at 600 nm as a function of potential is showing in Fig. 3 inset. The potential value for which half of the species V2+ are reduced
Fig. 4. Cyclic voltammograms of compound 1 (continuous line), 2 (dotted line) and 3 (dashed line) in 0.1 M NaClO4/DMF at 0.1 V/s scan rate versus Ag/AgCl.
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Table 2 Electrochemical parameters for the compounds 1–3 from cyclic voltammetrya. v
Epc1b
Epa1
Eo1c
DE1d
Epc2
Epa2
Eo2
DE 2
1
6
3.3 10
0.1 0.3 0.6 1
391 393 393 393
330 325 320 317
360 359 357 355
61 68 73 76
781 784 789 791
718 715 720 715
750 750 755 753
63 69 69 76
2
3.1 106
0.1 0.3 0.6 1
342 342 344 342
273 269 269 266
308 306 307 304
69 73 75 76
715 723 725 732
649 649 649 659
682 686 687 696
66 74 76 73
3
3.4 106
0.1 0.3 0.6 1
366 366 369 366
298 298 295 288
332 332 332 344
68 68 74 78
752 757 764 771
681 684 686 684
717 721 725 727
71 73 78 87
Compound
a b c d
D
All potential parameters are expressed in mV, the diffusion coefficients (D) in cm2 s1 and the scan rate (v) in V s1. Epc1, Epa1, Epc2 and Epa2 represent the corresponding half-wave potentials from CVs. Eo1 and Eo2 represent the calculated formal potentials. DE1 and DE2 represent the separation potential.
where D is the diffusion coefficient; B is the slope of the linear regression of the peak current (Ipc1) versus the square root of the scan rate; T is the temperature (298 K); A is the area of the surface of the electrode (0.031 cm2); z is the number of electron transferred (z = 1) and c is the concentration of the analyte in electrolyte solution (5 104 M). The compounds 1–3 have diffusion coefficients with relatively closed values and similar to well-known analogue 1,10 -dimethyl4,4-bipyridinium (paraquat), suggesting no self-association of dicationic species in DMF. The compound 1–3 were reduced at much more positive potential compared to well-known analogue 1,10 -dimethyl-4,40 -bipyridinium (E01 = 380 mV versus Ag/AgCl) measured in the similar experimental conditions [26]. The low positive potentials observed in the case of compounds 1–3 is attributed to the electronic effects of the substituents 9-(2-ethylene)adenine and/or 1-(3-propylene)thymine attached covalently to the nitrogen atoms. The formal potential values E01 and E02, corresponding to each electron transfer step, are more negative (approx. 60 mV) in the case of compound 1 compared with compound 2, while the formal potentials of compound 3 are situated between the values recorded for the compounds 1 and 2 (Table 2). The observed difference in the formal potential is explained by the charge transfer interaction between nucleobases as charge donors and 4,40 -bipyridinium core as charge acceptor. The dicationic state of the compound 1 was stabilized to a higher extent by charge transfer interaction with peripheral thymine group and therefore was reduced at a much negative potential than compound 2. The results from the electrochemical characterization are highly supported by the optical data which also suggests a higher charge transfer association constant in the case of compound 1 compared with compound 2, while compound 3 has an intermediary value. In the term of optical characteristics, the LUMO energy level of compounds 1–3, which is located on the acceptor moiety (4,40 bipyridinium) was affected by the charge transfer interaction with the pendant nucleobases. From electrochemical data was possible to calculate the exact energy of these molecular orbitals applying a calculation procedure reported in the literature [27]. We found a value of 4.11 eV for compound 1, 4.16 eV for compound 2 and 4.13 eV for compound 3, respectively. 4.4. Templated self-assemblies of viologen–thymine derivatives with homoadenylic oligonucleotides and analogue ssPNA The self-assembly approach of thymine-appended 4,4-bipyridinium derivatives with oligonucleotide dAn by adenine–thymine
hydrogen bonding was used to create highly ordered aggregates in solution exhibiting enhanced optoelectronic properties. In a first experiment two types of viologen–thymine derivatives were assembled in the presence of 40-mer adenylic oligonucleotide (dA40): type A (rode-like molecule 1) and type B (y-shaped molecule 4) [28] accordingly with the Scheme 2. The interaction of viologen–thymine derivatives 1 and 4, respectively with oligonucleotide dA40 was studied in a phosphate solution buffer (pH = 7). The components, i.e. viologen–thymine derivative (1 or 4) and oligonucleotide dA40, were mixed in an equimolar ratio of thymine/adenine units. The resulted mixtures were characterized by temperature-absorbance dependence experiments (Tm) and circular dichroism (CD) spectroscopy (Fig. 5). After mixing the components, a fraction of oligonucleotide dA40 precipitated as a result of competitive electrostatic interaction between polycationic scaffold of viologen–thymine derivatives and negatively charged riboso-phosphate backbone of dA40. The CD spectra (Fig. 5c and d) of the supernatant mixtures of 1:dA40 and G0:dA40, respectively showed that oligonucleotide dA40 coexists in solution with viologen–thymine compounds bellow a critical concentration and is expected to form hydrogen-bonded aggregates. The temperature-absorbance dependence experiments performed on supernatant mixtures 1:dA40 and G0:dA40 respectively, revealed a sharp increase of the nucleobase absorbance at 37 °C (Fig. 5a and b). The hyperchromic effect at 260 nm over the temperature is typical for the cooperative hydrogen bond breaking of thymine–adenine base pair in the dsA-T [1]. This results suggest that the unprecipitated dA40, remained in the supernatant solution, was hydrogen bonded with the complementary thymine appended viologen derivatives 1 and 4, respectively. Notably, the compound 4 showed a sharper hyperchromic effect compared to 1 in interaction with dA40 demonstrating a higher cooperativity of hydrogen bonding in the corresponding supramolecular aggregate. The possible self-assembled supramolecular models of compounds 1 and 4, respectively by hydrogen bonding with dA40 are presented in Scheme 2. In these models, the oligonucleotide dA40 plays the role of a template that directs the formation of an ordered fibrillar nanostructure. The two models are inspired by the plenty of examples in the literature referring to the ability of single stranded DNA to direct the formation of hydrogen-bonded supramolecular structures with fibrillar architectures [5–9,11,12]. The corresponding supramolecular aggregates are stabilized mainly by hydrogen bonding between the complementary nucleobases adenine and thymine units but other supramolecular forces, such as p–p staking or hydrophobic interactions between adjacent nucleobases
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Scheme 2. Self-assembly models of compounds type A: 1 and type B: 4 with ssDNA(dA40) as template by hydrogen bonding.
Fig. 5. Temperature-absorbance dependence experiment of compound 1 (a) and 4 (b) in the presence of dA40 in phosphate buffer (pH = 7). CD spectra dA40 in the absence (continue lines, c and d) and in the presence of compound 1 (c) and 4 (d) in phosphate buffer (dashed lines).
may also contribute energetically to the stabilization of the supramolecular assemblies, in a similar way as seen in the double stranded DNA (dsDNA). Further investigations in the solid state, i.e. crystallographic characterization, are in progress to confirm the proposed models.
In a second experiment, we studied the influence of the number of positive charges per molecule of 4,40 -bipyridinium-thymine derivative and the length of oligonucleotide in the same conditions as mentioned above. The compounds 1, 4 and a series of viologen-based dendrimers, with thymine units on the periphery
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Fig. 6. Temperature-absorbance dependence experiment of the aqueous solution mixtures of compound 4–7 with complementary adenylic PNA 10-mer (A10-PNA) in equimolar ratio T/A.
and polycationic scaffold [29] carrying 18 (5), 42 (6) and 90 (7) charges per molecule were used for the interaction with oligonucleotides dAn with different lengths (n = 20, 40, 80, 140). Except the compound 1 and 4 which produced a partial precipitation of oligonucleotide, the dendritic compounds (5–7) precipitated practically the entire amount of oligonucleotide dA40 (see supporting information). The amount of precipitated dAn increases with the increase of the number of positive charges per molecule of 4,40 -bipyridinium-thymine derivative and the length of the oligonucleotides dAn. In a third experiment, the behavior of derivatives 4–7 in the presence of analogue oligoadenylic PNA 10-mer was studied. The peptide nucleic acid (PNA) template have neutral backbone and no precipitation was observed. Tm measurements of aqueous mixtures of 4, 5, 6 and 7, respectively with PNA oligomer (A10-PNA) showed the same sharp hyperchromic transition at 260 nm with the temperature, typically for T@A hydrogen bonds breaking in double helix DNA (Fig. 6). The interaction mode between viologen–thymine derivatives and ssPNA-A10 was exclusively by hydrogen bonding. The results showed that the self-assembly process by hydrogen bonding is favored by the increase of the number of thymine units per viologen–thymine derivative, but becomes unfavorable with the increase of the number of positive charges due to the electrostatic interaction. Incorporation of viologen–nucleobase derivatives into a highly ordered supramolecular matrix by making use of hydrogen bonding ability of nucleobases to bind complementary templates is a promising approach to create new materials with enhanced optoelectronic properties. 5. Conclusions Nucleobase-appended viologens 1–3 were synthesized mainly by coupling the regioselective alkylated nucleobases to 4,40 -bipyridine unit by nucleophilic substitution reactions. They were characterized in the term of optical and electrochemical properties. A charge transfer interaction between the viologen unit as acceptor and nucleobases as donor was demonstrated by UV–Vis spectroscopy. The CT complexation has been influenced by the flexibility of the polymethylene linkage between nucleobase and viologen and by the nature of corresponding donor units (i.e. purinic or pyrimidinic base). The donor–acceptor relationship was found to affect optical characteristics of the viologen core in dicationic state and to play a significant role in the modulation of the necessary
energy required for the electron transfer (ET). Nevertheless, the electronic state or radical cation (V+) was not affected by the CT complexation upon electrochemical reduction since the compounds 1–3 had the typical blue color of ‘‘unconjugated’’ viologens such as 1,10 -dibenzyl-4,40 -bipyridinium derivative (DBV+). Thymine-appended viologens 1 and 4, differing in shape and number of nucleobase capping groups, were incorporated into a welldefined supramolecular matrix as optical/redox additives using the ability of thymine base to recognize and bind by hydrogen bonding complementary templates like oligonucleotides. The self-assembly process driven by thymine–adenine molecular recognition in aqueous solution has been demonstrated by optical methods (temperature-absorbance experiments and CD spectroscopy). Notably, the polycationic viologen–thymine derivatives were found to interact electrostatically with oligonucleotides beyond a critical concentration leading to ssDNA precipitation. Systematic studies were revealed that electrostatic interaction is strongly influenced by the oligonucleotide length and by the number of positive charges per viologen–thymine derivative. To avoid electrostatic interaction, which is undesirable for construction of hydrogen bonded self-assembled aggregates in solution, the oligonucleotides were replaced by peptide nucleic acids (PNA) with neutral backbone. The investigations in the presence of PNA template were extended to a series of four macromolecular viologen–thymine derivatives with dendritic architecture (4–7) and the optical characterization revealed that the self-assembly process was exclusively by hydrogen bonding. Construction of supramolecular templated aggregates with well-defined structure and size is of great importance for designing new materials with tuned optical or optoelectronic properties. The viologen derivatives appended by nucleobases have been proved to be excellent building blocks candidates for such purpose. Acknowledgements We gratefully thank our co-worker Ana-Maria Lepadatu for synthesis of the viologen-based dendrimers 4–7 used in the interaction studies with ssDNA and ssPNA. Appendix A. Supplementary material Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.optmat.2014.12. 044. References [1] W. Yang, P.F. Xia, M.S. Wong, Org. Lett. 12 (2010) 4018–4021. [2] B.Q. Ma, S. Gao, H.L. Sun, G.X. Xu, Cryst. Eng. Commun. 35 (2001) 1–5. [3] M. Möller, S. Asaftei, D. Corr, M. Ryan, L. Walder, Adv. Mater. 16 (2004) 1558– 1562. [4] H.J. Kim, J.K. Seo, Y.J. Kim, H.K. Jeong, G.I. Lim, Y.S. Choi, W.I. Lee, Sol. Energy Mater. Sol. C 93 (2009) 2108–2112. [5] H. Santa-Nokki, J. Kallioinen, J. Korppi-Tommola, Photochem. Photobiol. Sci. 6 (2007) 63–66. [6] Y. Kim, G.G. Malliaras, C.K. Ober, E. Kim, J. Nanosci. Nanotechnol. 10 (2010) 6869–6873. [7] Z. Sharrett, S. Gamsey, L. Hirayama, B. Vilozny, J.T. Suri, R.A. Wessling, B. Singaram, Org. Biomol. Chem. 7 (2009) 1461–1470. [8] P. Bhowmik, H. Han, I. Nedeltchev, J. Cebe, Mol. Cryst. Liq. Cryst. 419 (2004) 27–46. [9] K. Tanabe, T. Yasuda, M. Yoshio, T. Kato, Org. Lett. 9 (2007) 4271–4274. [10] S. Asaftei, M. Ciobanu, A.M. Lepadatu, E. Song, U. Beginn, J. Mater. Chem. 22 (2012) 14426–14437. [11] L.R. Rieth, R.F. Eaton, G.W. Coates, Angew. Chem. Int. Ed. 40 (2001) 2153–2156. [12] L. Brunsveld, B.J.B. Folmer, E.W. Meijer, R.P. Sijbesma, Chem. Rev. 101 (2001) 4071–4098. [13] B. Steiger, L. Walder, Helv. Chim. Acta 75 (1992) 90–108. [14] N. Baret, J.P. Dulcere, J. Rodriguez, J.M. Pons, R. Faure, Eur. J. Org. Chem. 8 (2000) 1507–1516.
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