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Spectral and Photophysical Behavior of Cytisine in NHexane. Experimental Evidence for the S(n,#*)#S Fluorescence 1

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Ewa Krystkowiak, Anna K. Przybyl, Malgorzata Bayda, Julia Józkowiak, and Andrzej Maciejewski J. Phys. Chem. A, Just Accepted Manuscript • DOI: 10.1021/acs.jpca.7b02280 • Publication Date (Web): 12 Jul 2017 Downloaded from http://pubs.acs.org on July 16, 2017

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The Journal of Physical Chemistry

Spectral and Photophysical Behavior of Cytisine in n-Hexane. Experimental Evidence for the S1(n,π π*)→ →S0 Fluorescence Ewa Krystkowiak*[a], Anna K. Przybył[a], Małgorzata Bayda[a], Julia Józkowiak[a], and Andrzej Maciejewski[a,b] [a] Faculty of Chemistry, Adam Mickiewicz University in Poznań, Umultowska 89b, 61-614 Poznań, Poland, E-mail: [email protected] (Ewa Krystkowiak) [b] Center for Ultrafast Laser Spectroscopy, Adam Mickiewicz University in Poznań, Umultowska 85, 61-614 Poznań, Poland

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Abstract: Spectral and photophysical properties of (−)-cytisine (the compound used as a smoking cessation aid and a potential drug in Alzheimer’s and Parkinson’s diseases) were investigated. The two conformers of cytisine, whose presence in the S0 state has been earlier proved by the NMR and IR methods as well as in theoretical calculation, in non-polar n-hexane show a rarely observed prompt fluorescence from the S1(n, π*) excited state. This observation is unambiguously evidenced by very small radiative rate constants of these two emitting conformers, kF= 7.4×105 s-1 and 3.0×105 s-1. Their lifetimes in the S1(n, π*) state are relatively long, ߬ୗభ = 1.9 ns and 6.7 ns, therefore their fluorescence quantum yield is relatively high φF∼ 10-3. The long-wavelength band in the cytisine absorption originates from the excitation to the S2(π,π*) state, while the S1(n, π*) state is not observed in this spectrum. Thus, the excited state S2(π,π*) is manifested only in the absorption spectrum, while the excited state S1(n, π*) – only in the fluorescence spectrum, so cytisine in n-hexane is characterized by close lying (n, π*) and (π,π*) excited singlet states.


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Introduction The fluorescence from singlet (π,π*) or intramolecular charge-transfer (ICT) electronic excited states, often with high fluorescence quantum yield is commonly observed, but prompt emission from excited singlet (n, π*) state of aromatic compounds has been relatively rarely observed.1-12 The S1(n, π*)→S0 fluorescence is characterized by very low quantum yields, φF, due to low values of the radiative rate constants, kF∼ 105−106 s-1, and relatively short S1-state lifetimes, ߬ୗభ (Table 1). More often the thermally activated fluorescence from S1(n, π*) state caused by small energy difference between the lowest singlet S1 and triplet T1 excited states is observed.13-18 In this case the S1(n, π*)→S0 fluorescence can be relatively intense because of a thermally activated T1→S1 pathway in the luminescent process from a long-lived T1-state. The emission spectra including fluorescence from S1(n, π*) state, have been measured for xanthone and quinoline in vapor phase, at different temperatures and pressures.13-14 This emission has not been observed upon decreasing temperature.15-18 (−)-Cytisine (see Fig. 1 for the structure) is a naturally occurring quinolizidine alkaloid extracted from seeds of Laburnum anagyroides and other Leguminosae plants.19 From the biological point of view, cytisine belongs to the family of antagonists of nicotinic acetylcholine receptors (nAChRs).20-21 It has been used as a smoking cessation aid (Tabex, Desmoxan) and is also a very promising compound for the development of new drugs for the treatment of central nervous system disorders, particularly Alzheimer’s and Parkinson’s diseases.22 It was shown that in solid state, cytisine prefers the chair conformation with the equatorially positioned hydrogen atom in the imine group of piperidine moiety.2326

Two conformers, axial (endo) and equatorial (exo) of the chair conformation of cytisine were found in

solution

25, 27-33

and in gas phase.31-34 DFT calculation performed for these two most stable cytisine

conformers reproduce very well the molecule in solution phase. The energy barrier for the NH inversion, calculated at the DFT level (3.6 kcal×mol-1), confirms coexistence of the two conformers (equatorial and axial) in the gas phase or apolar solvents. Their abundances are almost the same in the mixture (ca. 40 and 60%, respectively). This enables to distinguish the component FT-IR bands for both conformers in solution.31 Despite wide discussion of cytisine structure and computational study concerning ACS Paragon Plus Environment

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prediction of its bioavailability and physicochemical properties,32, 35 there are no literature data on UVVIS absorption and emission spectra as well as on photophysical study, except one absorption spectrum measured in water.36 Because of cytisine biological activity, such study seems to be of great importance for understanding the mechanism of its interactions with the environment. It is worth to note that a weak fluorescence in n-hexane solution (φF = 10-3 – 10-5) was previously reported for two alkaloids from lupine class whose structures are similar to that of cytisine (see Table 1).37 In the present work, we discuss the results of spectral and photophysical study of (−)-cytisine in nhexane, which disclose a rarely observed fluorescence from S1(n, π*) excited state of two conformers.

Table 1. Spectral and photophysical properties of the selected aromatic and quasi aromatic compounds containing carbonyl group and displaying the S1(n, π*)→S0 prompt fluorescence.

Compound

Solvent

εmax/ M-1 × cm-1

߬ୗభ / ns

φF

kF/ s-1

knr/ s-1

Ref.

coumarin

cyclohexane

5 700

≤0.10

3×10-4

≥3×106

≥1×1010

1

3-chlorocoumarin

cyclohexane

7 200

≤0.10

4×10-4

≥4×106

1×1010

1

khelin

cyclohexane

1.2

2×10-4

2×105

8×108

2

lupanine

n-hexane

8 200

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TOC Graphic

S1(n,π π*)

20000

S0

25000

S0

30000

S2(π π,π π*)

35000 ν / cm

-1


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Spectral and Photophysical Behavior of Cytisine in ... - ACS Publications

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