A novel dual channel responsive zinc(II) probe

Tetrahedron Letters xxx (2014) xxx–xxx

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A novel dual channel responsive zinc(II) probe Serkan Karakaya a, Fatih Algi a,b,⇑ a b

Laboratory of Organic Materials (LOM), Çanakkale Onsekiz Mart University, TR-17100 Çanakkale, Turkey Department of Biotechnology and Molecular Biology & ASUBTAM BioNanoTech Lab., Aksaray University, TR-68100 Aksaray, Turkey

a r t i c l e

i n f o

Article history: Received 9 July 2014 Revised 25 July 2014 Accepted 13 August 2014 Available online xxxx Keywords: 1,10-Phenanthroline Zn(II) Fluorescence Colorimetric Probe BODIPY

a b s t r a c t A novel compound, 1, which is based on a 1,10-phenanthroline scaffold with cofacial BODIPY units, is synthesized via a three-step reaction sequence. It is noteworthy that 1 can be utilized for both visual and turn-off fluorometric detection of Zn2+ ions in aqueous acetonitrile solution. The fluorescence response is based on cation-mediated oxidative photoinduced electron transfer (PET). The digital action of a two-input NOR logic gate is also demonstrated. Ó 2014 Elsevier Ltd. All rights reserved.

In supramolecular chemistry, considerable efforts have been devoted to the design and synthesis of functional organic materials, which allow selective and sensitive detection of target metal ions, since metal ions play deleterious and/or essential roles in biological and environmental processes.1 Among these ions, zinc is one of the most abundant transition metals in many organisms, and it is essential to life by being the only metal which appears in nearly all enzymes. Zinc plays important roles in many biological processes, including regulation of apoptosis, signal transmission, enzyme function, and gene expression.2a It is also reported that zinc is associated in a number of pathological processes, such as diabetes2b and Alzheimer’s disease.2c Therefore, designing novel molecular probes which can selectively recognize zinc among other metal ions is a challenging task. It should also be noted that the electronic configuration (3d10 4s0) of zinc(II) makes it spectroscopically silent toward many optical detection methods. Fortunately, however, fluorescence spectroscopy offers a highly efficient method for the detection of zinc(II) ions. Thus, many examples of fluorescent zinc(II) sensors have been reported to date in the literature.3 Photoinduced electron transfer (PET) is one of the most prominent phenomena in the design of fluorescent molecular probes.4,5 In principle, PET might occur in two different directions.5 In the first case, PET takes place from a donor unit to the excited-state fluorophore, which is termed reductive PET. On the other hand, ⇑ Corresponding author. Tel.: +90 3822882138; fax: +90 3822882185.

PET might also occur from an excited-state fluorophore to an acceptor unit, which also acts as a receptor. The second case is known as oxidative PET. Both of these processes are accompanied by quenching of the fluorophore emission. Although oxidative PET is well-known,5 it has been hardly used in chemosensor applications. It is generally observed in bipyridyl fluorophores where the conjugation of bipyridyl and fluorophore units is interrupted by either saturated carbons or by the orthogonal geometry of those units.6 The fluorescence of the receptor-fluorophore is quenched upon binding of the guest. Boradiazaindacenes (BODIPYs) are an important class of fluorescent dyes due to their unique photophysical characteristics, which include high molar absorption coefficients, high fluorescence quantum yields, good chemical, thermal, and photostability, and narrow emission band widths. An additional advantage of this class of compounds is that their visible excitation and emission can be tuned by structural modification of the pyrrole core through its rich chemistry. Consequently, these features have made BODIPYs excellent candidates for biological labeling, artificial light harvesters, fluorescent switches, and chemosensors.7 Additionally, polymeric BODIPYs,8,9 have recently been added to the repertoire of macromolecular systems, which are now finding an increasing number of applications in both materials and optical imaging fields. We have previously reported that cation-mediated oxidative PET can be modulated in a very rigid arrangement.10 We designed a novel compound which was based on a 1,10-phenanthroline scaffold with cofacial BODIPY units attached orthogonally as the

E-mail address: [email protected] (F. Algi). http://dx.doi.org/10.1016/j.tetlet.2014.08.059 0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.

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S. Karakaya, F. Algi / Tetrahedron Letters xxx (2014) xxx–xxx

F B N N

F F N B N

F

OHC

CHO

a N

N

R

b N

N

2

3

N

NH

4

c

N 5 R=CH3 1 R=

N Scheme 1. Reaction conditions: (a) SeO2, 1,4-dioxane-water (4%, v/v), 100 °C, 60%; (b) TFA, CH2Cl2, chloranil, BF3
OEt2, 20%; (c) 4-dimethylaminobenzaldehyde (6), HOAc, piperidine, benzene, 80 °C, 51%.

Figure 1. UV–vis absorption spectra of 1 (5  10 5 M) in 10% aqueous CH3CN (v/v) solution upon addition of Zn2+ ions (0.0–5  10 3 M).

receptor and fluorophore units, respectively. This design afforded a turn-off fluorescent Cd(II) probe. We wondered if a simple modification could allow us to tailor the selectivity of this probe from Cd(II) to Zn(II) (vide infra). It is important to note that these analytes, Cd(II) and Zn(II), are in the same group of the periodic table and they show very similar properties. Removing the possible disruptive effects of other metal ions such as Cd(II), Cu(II), and Ni(II) was also critical in the design.

Figure 2. (a) Chromogenic and (b) fluorogenic responses of 1 (5  10 UV illumination (365 nm), respectively.

5

In this Letter, we report our research concerning the design, synthesis, and properties of novel material 1 based on 1,10-phenanthroline and BODIPY units. It is noteworthy that 1 can be utilized as a selective dual channel (colorimetric and fluorometric) responsive Zn2+ probe in aqueous solution. The fluorescence response of 1 is based on cation-mediated oxidative PET. Importantly, the modulation of BODIPY emission in a highly rigid arrangement by cation-mediated oxidative PET in aqueous solution was achieved to afford a highly selective fluorescent Zn2+ probe. Interestingly, the digital action of 1 as a two-input NOR6a,b logic gate was also illustrated. The synthesis of the target compound was carried out via a three-step sequence. Initially, 4,7-dimethyl-1,10-phenanthroline (2) was treated with SeO2 in refluxing 1,4-dioxane-water to afford bisaldehyde 3 in 60% yield according to a known procedure (Scheme 1).11 Next, condensation of 3 with 2,4-dimethyl-3-ethylpyrrole (4) in the presence of a catalytic amount of trifluoroacetic acid (TFA) resulted in the formation of a dipyrromethane, which was then oxidized by chloranil to generate the corresponding dipyrromethene. Complexation with BF3
OEt2 provided 5, albeit in 20% yield (Scheme 1). Finally, Knoevenagel-type condensation of 5 with 4-dimethylaminobenzaldehyde (6) afforded the target compound. Compound 1 was initially characterized on the basis of 1H and 13 C NMR spectroscopy and elemental and MALDI-TOF analysis, which firmly established the structure (see Supporting information, Figs. S4–S6). The absorption profile of 1 was examined in solution. The UV– vis spectrum of 1 in 10% aqueous CH3CN (v/v) solution was characterized by absorption bands centered at 234, 264, 320, 374, 524, and 629 nm with extinction coefficients (e) of 177401, 125588,

M) to Zn2+ ions and TFA (0.0–5  10

3

M) in 10% aqueous CH3CN (v/v) solution under room light and

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S. Karakaya, F. Algi / Tetrahedron Letters xxx (2014) xxx–xxx

N F F B N N

F F N B N

N

Zn2+

N F F B N N

N

F F N B N

N

N

Zn2+ Scheme 2. Zn(II) recognition of probe 1.

Figure 3. Fluorescence emission spectra of 1 (1.0  10 6 M) in 10% aqueous CH3CN (v/v) solution in the presence of various metal cations (1 equiv). The emission data of 1 were recorded at 549 nm; excitation was at 510 nm.

81005, 71881, 212386, and 72606 M 1 cm 1, respectively, (Fig. S7). The metal cation complexing properties of 1 were investigated in the same solution by UV–vis spectrophotometric titrations with different metal ions. It was found that the absorption of 1 was not influenced at all upon the addition of Ag+, Al3+, Au3+, Cu+, Cu2+, Cd2+, Fe2+, Fe3+, Hg2+, K+, Li+, Mg2+, Mn2+, Na+, Ni2+, Pb2+, Pd2+, and Pt2+ ions, all of which gave no significant change in the absorption spectrum of 1 as shown in Figure S7. To our delight, however, it was noted that Zn2+ ions revealed significant changes in the maxima of the original absorption spectrum of 1. Figure 1 shows the absorption spectral changes of 1 as a function of the

Zn2+ concentration in 10% aqueous CH3CN (v/v) solution at room temperature. Notably, a progressive decrease in the absorbances at 234, 264, 320, 374, and 524 nm was observed with a simultaneous red shift (15 nm) of the absorption band at 629 nm. Furthermore, these shifts in absorption bands were enough to change the color of the solution from grape to purple, thus allowing naked-eye (colorimetric) detection of Zn2+ ions among other ions (Fig. 2, Scheme 2). It is important to note that a color change is one of the most convenient visual detection methods used in classical chemical analysis, along with being straightforward and inexpensive. On the other hand, compound 1 was highly fluorescent in the same solvent mixture and the fluorescence emission spectrum of 1 exhibited a broad emission peak with a kmax(emis) at 549 nm (kexc = 510 nm). The quantum yield (uf) was determined to be 0.165 in reference to fluorescein (uf = 0.925 in 1 M aqueous NaOH).10 It was found that the addition of Ag+, Al3+, Au3+, Cu+, Cu2+, Cd2+, Fe2+, Fe3+, Hg2+, K+, Li+, Mg2+, Mn2+, Na+, Ni2+, Pb2+, Pd2+, and Pt2+ ions did not induce any significant change in the emission profile of 1 (Fig. 3). However, the emission of 1 (1.0 lM) was quenched upon the addition of Zn2+ ions (turn-off). Figure 4 illustrates the relative fluorescence emission intensity of 1 in the presence of various metal cations in 10% aqueous CH3CN (v/v) solution. Figure 5 depicts the fluorescence spectral changes of 1 (1.0 lM) as a function of Zn2+ concentration (0.0–3.0 equiv) in 10% aqueous CH3CN (v/v) solution at room temperature. It is important to note that a progressive decrease in the fluorescence emission intensity at 549 nm was observed as the concentration of the ion was increased.

Figure 4. Relative fluorescence emission intensity of 1 (1.0 lM) in the presence of various metal cations (1 equiv) in 10% aqueous CH3CN (v/v) solution. The emission data of 1 were recorded at 549 nm; excitation was at 510 nm.

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S. Karakaya, F. Algi / Tetrahedron Letters xxx (2014) xxx–xxx Table 1 Fluorescence emission response of 1 in accordance with NOR logic gate behavior Input 1 0 3.0  10 0 3.0  10

Figure 5. Fluorescence spectra of 1 (1.0  10 6 M) as a function of various amounts (0.0, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.5, 2.0, 2.5, and 3.0 equiv) of Zn2+ ions in 10% aqueous CH3CN (v/v) solution at room temperature (kexc = 510 nm).

The changes in the emission profile of 1 upon the addition of Zn2+ ions indicated the formation of a well-defined complex between 1 and Zn2+. Evaluation of the Job plot for the determination of the stoichiometry of the interaction between 1 and Zn2+ revealed a 1:1 ratio (see Supporting information, Fig. S8). Upon binding of Zn2+ ions to 1, the fluorescence emission of the BODIPY unit was quenched through oxidative PET. It is assumed that both the HOMO and LUMO energy levels of the metal-bound form of the ligand 1 favor electron transfer for oxidative PET when compared

Figure 6. Partial 1H NMR (CD3OD) spectrum of 1 (upper) and the 1-Zn2+ complex (lower).

Input 2 6

6

M Zn2+ M Zn2+

0 0 0.7  10 0.7  10

Output

3 3

M TFA M TFA

1 0 0 0

to the metal-free state, thus providing efficient nonradiative decay of the excited state. The interaction between 1 and Zn2+ was also proven by 1H NMR spectroscopy (Fig. 6) and mass spectrometry (Fig. S9). It was observed that the binding of Zn2+ mainly affected the protons of the phenanthroline ring of 1, which shows down field shifts (Dd = 0.07–0.18 ppm) in the 1H NMR spectrum. On the basis of the above spectrophotometric titrations, the binding constant (Ka) of 1 with Zn2+ was determined from the emission intensity data following the steady-state fluorometric method,1f–h,10a,12 in which I0 refers to the fluorescence intensities of solutions of 1. When I0/(I I0) is plotted against [M] 1, Ka was calculated to be 1.06  106 from the ratio of the intercept/slope with a good correlation coefficient (R = 0.98531) (see Supporting information, Fig. S10). Interestingly, it was found that the emission of 1 was also quenched by the addition of a small amount of trifluoroacetic acid (TFA, 13 mM final concentration) to a 10% aqueous CH3CN (v/v) solution of 1 at room temperature, as in the case of Zn2+. Most probably, this can be explained on the basis of the fact that protonation of the dimethylamino and phenanthroline units facilitates oxidative PET as with chelation to the metal ion. Additionally, the interaction of 1 with TFA can be observed by the naked-eye (Fig. 2 and Fig. S11). These observations led us to explore the possibility of NOR6a,b logic gate13 behavior for probe 1. Fortunately, the addition of both chemical inputs produced a quenched signal (Table 1). It should be noted that residual emissions in both Zn2+ and TFA solutions of 1 were nearly at the same level indicating the off state (see Figs. 5 and 7). Thus, the remarkable digital action of a two-input NOR logic gate was demonstrated. In conclusion, the design and synthesis of a novel dual channel responsive Zn2+ probe, which is based on a 1,10-phenanthroline scaffold with cofacial BODIPY units, has been described. It is noteworthy that the fluorescence response of 1 is based on cation-mediated oxidative PET, which is rarely utilized in sensing

Figure 7. Fluorescence spectra of 1 (0.7  10 6 M) as a function of TFA concentration (0.0–0.7  10 3 M) in 10% aqueous CH3CN (v/v) solution at room temperature (kexc = 510 nm).

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S. Karakaya, F. Algi / Tetrahedron Letters xxx (2014) xxx–xxx

applications. Last, but not least, the remarkable digital action of a two-input NOR logic gate was also demonstrated. Further work along these lines is currently underway in our laboratory. Acknowledgements The authors are grateful to the Scientific and Technological Research Council of Turkey (TUBITAK, Grant No. 112T668), and European Cooperation in Science and Technology (EU COST) for partial financial support. S.K. is indebted to TUBITAK for a graduate fellowship and the Teaching Staff Training Programme (OYP) of the Turkish Council of Higher Education (YOK). Supplementary data

4.

5. 6.

Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.tetlet.2014.08. 059.

7.

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