Tunable Solvatochromic Response of Newly Synthesized

ARTICLE pubs.acs.org/JPCA

Tunable Solvatochromic Response of Newly Synthesized Antioxidative Naphthalimide Derivatives: Intramolecular Charge Transfer Associated with Hydrogen Bonding Effect Sayaree Dhar,† Somnath Singha Roy,‡ Dipak Kumar Rana,† Sudin Bhattacharya,‡ Sumanta Bhattacharya,§ and Subhash Chandra Bhattacharya*,† †

Department of Chemistry, Jadavpur University, Kolkata 700032, India Department of Cancer Chemoprevention, Chittaranjan National Cancer Institute, 37, S. P. Mukherjee Road, Kolkata 700026, India § Department of Chemistry, The University of Burdwan, Golapbag, Burdwan 713104, India ‡

ABSTRACT: The solvatochromic behavior of two newly synthesized naphthalimide derivatives (I and II) which have potential antioxidative activities in anticarcinogenic drug development treatment, has been monitored in protic and aprotic solvents of different polarity applying steady-state and timeresolved fluorescence techniques. The compounds exhibit unique photophysical response in different solvent environments. The spectral trends do not appear to originate only from changes in the solvent polarity but also indicate that hydrogen bonding interactions and intramolecular charge transfer (ICT) influence the energy of electronic excitation of the compounds. Incorporation of an amino group at C(4) position of the naphthalimide ring in II makes it behave differently from I in terms of spectral characterization and fluorescence efficacy of the systems. The nonradiative relaxation process of the compounds is governed by medium polarity. The ground state geometry, lowest energy transition, and the UV-vis absorption energy of the compounds were studied using density functional theory (DFT) and time-dependent density functional theory (TDDFT) at the B3LYP/6-31G* level, which showed that the calculated outcomes were in good agreement with experimental data.

’ INTRODUCTION Intramolecular charge transfer (ICT) has been a topic of increasing interest both in photochemistry and in biochemistry because it is a possible mechanism for biological and chemical energy conversion.1-6 The excited-state electron transfer in organic donor-acceptor compounds is usually described in terms of electronic coupling between the locally excited (LE) state and the charge transfer (CT) state.7 This process will lead to a large increase of the dipole moment and, hence, will cause a marked solvatochromic effect and a large Stokes shift. Investigations of organic molecules possessing ICT are focused on systems in which donor and acceptor groups are directly connected through a single bond or π bond.8 The interaction through a single bond is focused on through-space interaction between the donor and acceptor,9 and the interaction through a π bond is concentrated on orbital overlap between donor and acceptor groups.10-12 Hydrogen bonding and solvent polarity are the key factors in controlling pathways of energy dissipation following electronic excitation.13,14 Solvent-moderated shifts of the energy levels may enhance or inhibit radiationless transitions to the ground state via the “proximity effect”.15 Hydrogen bond formation has a different effect on the energies of various excited states; in an extreme r 2011 American Chemical Society

case, hydrogen bonding may cause the reversal of close lying n, π* and π, π*states.16 The development of chemical systems as structural probes in biological macromolecules, as well as therapeutic agents, has led to the design of novel compounds that have specific activities and interactions with biological systems. To attain the desired reactivity, the compound must interact, specifically and noncovalently, with the target of interest and demonstrate appropriate thermal or photochemical activity with the target. Of the compounds that have been studied, naphthalene-based imide and diimide compounds have been shown to exhibit novel reactivities. The compounds are readily derivatized, through the imide nitrogen, and have a variety of functional groups that “tune” the specific interactions with target molecules. Naphthalimide (isoquinolindione) derivatives, which are characterized by the presence of a coplanar fluorophore and, usually, a π-deficient aromatic system, as well as one or two basic side chains, constitute an important class of prodrugs in anticancer therapy showing a broad spectrum of activity against a Received: December 11, 2010 Revised: February 2, 2011 Published: March 02, 2011 2216

dx.doi.org/10.1021/jp1117773 | J. Phys. Chem. A 2011, 115, 2216–2224

The Journal of Physical Chemistry A variety of murin and human solid tumor cells.17,18 Two members of this class of compounds, amonifide and mitonafide, are used in clinical trials.19 Naphthalimide systems have been shown to be effective intercalating agents with DNA. For example, N-alkylamine substituted naphthalimides have been found to exhibit selective binding toward -GC- base pair regions.20 Their DNA binding or enzyme inhibitory activity is believed to be pivotal to exert antitumor effect. The oxidative nature of naphthalimides, coupled with their ability to intercalate DNA bases, has been used in DNA photocleavage reactions.21 Moreover, similar derivatives have been proposed as good candidates for the photochemical inhibition of enveloped viruses in blood and blood products22 and for the fluorescent probing of hypoxic cells.23 1,8-Naphthalimides comprise a class of chromophores for which excited state properties can be drastically changed by the nature of the substituent present in the aromatic ring.21,24,25 The photophysical behavior of these derivatives is a function of C(4) substitution.26 While the nonpolar π, π* state occurs in the parent naphthalimide (i.e., without any substituents at the 4 position), the introduction of electron-donating or -withdrawing substituents (amino or nitro groups) induces a polar CT excited state.25 The compounds with CT character are especially interesting due to their strong oxidizing or reducing capacity. Because of their strong fluorescence and good photostability, the 1,8-naphthalimide derivatives have found application in a number of areas including coloration of polymers,27 laser active media,28 potential photosensitive biological units,29 fluorescent markers in biology,30 analgesics in medicine,31 light-emitting diodes,32 photoinduced electron transfer sensors,33 fluorescence switchers,34 electroluminescent materials,35 liquid crystal displays,36 and ion probes.37 In the present work, we intend to study the photophysical properties of two newly synthesized 1,8-naphthalimide derivatives (I and II in Scheme 1) which have potential to downregulate the oxidative stress at the preliminary stage of carcinogenesis,38 in solvents of varying polarity as well as hydrogen bonding ability. Our aim is to study the solvent-dependent radiative transitions and relaxation dynamics from the excited singlet state. Solvatochromic behavior of the compounds can be explained by the combined effect of ICT and dye-solvent specific hydrogen bonding interaction. The results obtained from the steady-state and time-resolved fluorescence studies in protic and aprotic solvents have been rationalized on the basis of solvent-solute interaction. A comparative study of the kinetics of the fluorophores in different solvents has been presented.

’ EXPERIMENTAL SECTION Materials. Compound I (2-(5-selenocyanato-pentyl)-benzo[de]isoquinoline-1,3-dione) was synthesized following the procedure mentioned in the synthesis scheme described earlier.38 4-Amino naphthalimide, the starting material for the synthesis of compound II (2-(5-bromo-pentyl)-6-amino benzo[de]isoquinoline-1,3-dione), was obtained from Sigma-Aldrich and was used for synthesis without further purification. All the solvents 1,5-dibromopentane, dioxan (DIOX), tetrahydrofuran (THF), dimethylformamide (DMF), acetonitrile (ACN), ethanol (EtOH), methanol (MeOH), ethylene glycol (EG), cyclohexane (CYHX), and n-heptane (HEP) used were all from E. Merck (HPLC grade). The solvents were dried according to the method described elsewhere.39 The purified and dried solvents were transparent in the spectral region of interest. Millipore

ARTICLE

Scheme 1. Schematic Representations of the Naphthalimide Derivatives (I and II) Investigated in the Present Study after the Geometrical Optimization

water was used for the preparation of aqueous solutions. The stock solution of compounds (2 10-3 M) was prepared in dioxan, and a fixed amount of these concentrated solutions were added to each experimental solution. In the micromolar concentration range, the probe molecules in polar aprotic and protic solvents do not aggregate and remain in a molecularly dissolved state. Methods. For synthesis all reactions were conducted under anhydrous condition, solvents (DMF, MeOH) were well dried, and reactions were performed using oven-dried glassware. Melting points were determined on a capillary melting point apparatus (SMP3 Apparatus (Bibby, STERILIM, U.K.)) without correction. NMR spectra were recorded with Bruker AC-300 MHz NMR spectrometer on a 300 MHz for proton and 75 MHz for carbon in CDCl3 solution using tetramethylsilane as the internal reference. The coupling constant (J) is reported in hertz. The mass spectrum was recorded on JMS600 in an EI ionization mass spectrometer. Elementary analyses were recorded on PerkinElmer auto analyzer 2400II. Column chromatography was performed using silica gel (60-120 mesh) (Qualigen India). A Shimadzu (model UV1700) UV-vis spectrophotometer and a Spex fluorolog-2 (model FL3-11) spectrofluorimeter with an external slit width of 2.5 mm were used to collect absorption and fluorescence spectra, respectively. All measurements were done repeatedly, and reproducible results were obtained. All fluorescence spectra were corrected for instrumental response. Prior to the spectroscopic measurements solutions were deoxygenated by bubbling nitrogen through them. The fluorescence quantum yield (Φf) was measured relative to quinine sulfate (Φf = 0.54 in 0.1 M H2SO4).40 Fluorescence lifetimes were determined from time-resolved intensity decay by the method of timecorrelated single-photon counting using a nanosecond diode laser both at 403 nm (IBH, picoLED-07) and at 370 nm (IBH, picoLED-03) as light source. The typical response times of the laser system at 403 and 370 nm were 70 ps and 1.1 ns, respectively. The data stored in a multichannel analyzer were routinely transferred to IBH DAS-6 decay analysis software. For all the lifetime measurements the fluorescence decay curves were analyzed by single and biexponential iterative fitting program provided by IBH such as FðtÞ ¼

∑i Ri expð - t=τi Þ

where Ri is a pre-exponential factor representing fractional contribution to the time-resolved decay of the component with a lifetime τi. Mean (average) lifetimes Æτæ for biexponential decays of fluorescence were calculated from the decay times 2217

dx.doi.org/10.1021/jp1117773 |J. Phys. Chem. A 2011, 115, 2216–2224

The Journal of Physical Chemistry A

ARTICLE

Scheme 2. The Synthesis Route of Compound II [2-(5-Bromopentyl)-6-aminobenzo[de]isoquinoline-1,3-dione]

Synthesis. Compound II was synthesized following a onestep procedure as shown in Scheme 2. To a magnetically stirred solution of 4-aminonaphthalimide (1.0 g, 4.7 mmol) in dry DMF (50 mL), a methanolic solution of sodium methoxide (5 mL of a solution of sodium (783 mg) in MeOH (10 mL, 4.7 mmol)) was added dropwise at room temperature. After the mixture was stirred for 1 h, 1,5-dibromopentane (2.53 mL, 0.018 mol) was added to the brown solution and stirring continued for another 15 min. The reaction was quenched with 250 mL of ice cold water to yield a yellow solid as the product. It was purified by column chromatography over silica gel (petroleum ether (6080 C)/CHCl3 (1:1, v/v). Yield 1.43 g (84%). Mp 158-159 C. 1 H NMR (CDCl3, 300 MHz) δ: 1.54-1.98 (m, 6H, 3 CH2), 3.425 (t, 2H, J = 6.3 Hz, CH2Br), 4.168 (t, 2H, J = 7.2 Hz, CH2N), 4.979 (s, 2H, NH2), 6.89 (d, 1H, J = 8.1 Hz, Ar-H), 7.659 (t, 1H, J = 7.8 Hz, Ar-H), 8.12 (d, 1H, J = 8.1 Hz, Ar-H), 8.42 (d, 1H, J = 8.1 Hz, 5-H), 8.6 (d, 1H, J = 7.2 Hz, Ar-H). 13C NMR (CDCl3, 75 MHz) δ: 25.68, 27.23, 32.45, 33.64, 39.80, 109.57, 112.15, 120.08, 123.11, 124.99, 126.82, 129.79, 131.48, 133.77, 149.08, 163.99, 164.54. MS (ESþ): 383.04 and 385.04(Mþ þ Na).

’ RESULTS AND DISCUSSION

Figure 1. Normalized absorption profile of the compounds in different solvents: (a) compound I; (b) compound II.

and pre-exponential factors using the following equation hτ i ¼

R1 τ 1 þ R2 τ 2 R1 þ R2

Geometrical optimization and ground state dipole moment calculations were performed using semiempirical molecular orbital methods at the Austin model 1(AM 1) level using MOPAC program. For the theoretical study of excited state photophysics of the compounds, we used the Gaussian 03 package. The ground state geometries of the compounds were optimized using Becke’s three-parameter hybrid exchange functional with the LeeYang-Parr correlation functional (B3LYP) method in conjunction with the 6-31þG* basis set. Computations of the vertical excitations, difference density plots, and optimization of the excited states were performed using time-dependent DFT, the B3LYP functional (TD-B3LYP), and the 6-31þG* basis set. The HOMO and LUMO frontier orbital of the compounds were calculated by TD-DFT methods at the B3LYP/6-31G* level.

Solvent-Assisted Absorption and Emission Behavior. The UV-vis absorption spectra and fluorescence spectra of the compounds have been studied in various solvents of different polarity. A few representative absorption spectra in different nonpolar and polar solvents are shown in Figure 1 and the corresponding spectral data are reported in Table 1. Compound I exhibits one broad absorption band centered at 343 nm in water which can be related with the strong π, π* transition while the small shoulder around 295 nm can be related to an n, π* transition of similar energy.41 From an inspection of the spectroscopic values of I in various solvents of different polarity, it is obvious that the ground state of I depends on the polarity of the homogeneous medium. Decreasing solvent polarity and proticity, the vibrational fine structure appears in the band at 346 nm (Figure 1a). In HEP and CYHX, the vibrational splitting is intense. As the polarity is increased the π, π* absorption band (at 330 nm) shifts to a lower energy, whereas the vibrational band (at 346 nm) shifts to a higher energy. The red shift takes place in the electronic transition of the type π, π* transition as there is a high degree of coplanarity between the π system of the naphthalene ring and imide nitrogen. The absorption spectra of compound II (Figure 1b) consists of a broad, featureless, longest wavelength band centered at 432 nm. A change of the solvent from HEP to water results in a large (39 nm) bathochromic shift of the absorption maximum of II. The magnitude of this shift suggests that the ground state of II 2218



ARTICLE

Table 1. Photophysical Parameters of the Compounds in Different Solvents λabs max (nm)

λem max (nm)

molar extinction coeff. (dm3 mol-1 cm-1)

Δv (cm-1)

I

II

I

II

I

II

I

II

ET(30) (kcal mol-1)

water

343

432

396

544

5778

4492

3902

4766

63.1

EG

337

436

390

531

8327

6640

4032

4103

56.3

MeOH

333

434

386

530

8497

7148

4123

4174

55.5

EtOH

333

436

385

524

8497

6953

4056

3852

51.9

ACN

332

418

381

536

8327

6679

3874

5267

46.0

DMF

334

432

381

518

8723

6875

3693

3843

43.9

THF

332

419

375

514

9006

6718

3454

4411

37.4

DIOX CYHX

332 330

412 394

374 368

516 510

8836 9233

6445 6133

3382 3129

4892 5773

36.3 31.2

HEP

330

393

366

510

8497

5820

2980

5837

31.1

solvent

Figure 3. Variation of Stokes shift as a function of solvent polarity parameter of compound I; inset represents the same for compound II.

Figure 2. Normalized emission profile of the compounds in different solvents: (a) compound I; (b) compound II.

is significantly polar. This band arises because of an intramolecular charge transfer from the 4-amino group to the naphthalimide ring system, and this is evident from the following observations: the absorption is fairly broad and intense, the peak position is rather sensitive to the polarity of the medium (Table 1), 4-unsubstituted naphthalimides do not exhibit this band42 and 4-amino-1,8-naphthalimide25,43,44 and 4-alkylamino)amino substituted 1,8-naphthalimide,45 which possess an electron-donating group at the 4-position, display a similar band. The emission spectra of I (Figure 2a), excited at 343 nm, show a single large red-shifted band in the region of 376-396 nm on going from DIOX to water. The effect of the polarity of the medium on the fluorescence maximum is more pronounced than that on the absorption maximum. This observation suggests that the emitting state of I is more polar than the ground state. The

emission spectra are more prominent in polar solvents compared to that in nonpolar solvents. The fluorescence data of compound I can be rationalized in terms of two closely spaced n, π* and π, π* states. That a close proximity of two such states can alter the photophysical behavior of systems containing nonbonding and π electrons is well established in the literature.13,46-48 With the change of the polarity of the media, the relative ordering and spacing between these states are altered, resulting in a change in the luminescing ability of the system. In polar solvents, however, the rate of this intersystem crossing is considerably reduced,46 owing to a larger separation between the two states. Consequently, an enhancement of fluorescence is expected in polar solvents. The fluorescence spectra recorded for II (Figure 2b) upon excitation at 432 nm are structureless bands centered in the region 510-544 nm on going from HEP to water and the fluorescence spectral data are presented in Table 1. The emission spectra of II are characterized by broad bands typical of an ICT transition within the fluorophore.49 Due to ICT character, the lone pairs are not free and the n, π* transition is absent in nonpolar solvent. Since Stokes shift (Δv, difference between the transition energy corresponding to the absorption maxima E(A) and the transition energy corresponding to the fluorescence maxima E(F)) is usually better correlated to the microscopic solvent polarity parameter, ET(30),50 we have studied this correlation graphically (Figure 3) for I and II. Interestingly, compound II shows double linear correlation with ET(30) and the nature of correlation is entirely different for these two compounds. 2219



ARTICLE

Table 2. The Contribution of Hydrogen Bonds, Change in Free Energy of Solvation, and Reorganaisation Energies of the Compounds in Different Solvents Δv shift (H-bond) (cm-1) I solvent Abs water

ΔG (kcal mol-1)

λ (kcal mol-1)

II Em

Abs

Em

1149 2070 2297 1225

I

II

I

II

77.5

59.2

5.56

6.79

EG

629 1681 2510

775

78.8

59.5

5.75

5.85

MeOH

273 1416 2404

740

79.7

59.7

5.87

5.95

EtOH

273 1348 2510

524

79.8

59.9

5.78

5.49

ACN DMF

183 1076 1522 363 1076 2297

951 303

80.3 80.1

60.7 60.5

5.52 5.26

7.50 5.48

THF

183

656 1579

153

80.9

61.7

4.92

6.28

DIOX

183

584 1173

228

81.0

62.2

4.82

6.97

CYHX

0

0

0

0

81.9

64.1

4.45

8.22

HEP

0

0

0

0

82.1

64.2

4.24

8.31

In compound II, the Stokes shift decreases sharply on going from water to EtOH and then rises steeply on changing from DMF to HEP. The results obtained so far suggest that the Stokes shift of the compounds in different solvents is governed by three factors: solvent polarity; hydrogen bonding, and ICT. In the case of polar protic solvents, hydrogen bonding is expected to cause a sudden increase of Stokes shift, followed by a steep increase from polar aprotic to nonpolar solvent mainly due to the occurrence of an ICT in the more nonpolar solvent region. Compound I exhibits an overall increase of Stokes shift from nonpolar to polar solvent mainly due to the combined effect of both hydrogen bonding and polarity of the medium. Comparing this profile of both compounds, one observes that II displays both the hydrogen-bonding interaction as well as ICT and the latter is less prominent in case of compound I. It is possible to extract the contributions of the specific interactions (hydrogen bonds) on the experimentally observed spectral shifts of the compounds.51 This procedure is based on an em analysis of the solvatochromic dependencies of vabs max and vmax on the solvent polarity function, Δf, of the solvents used where Δf ¼

ε-1 n2 - 1 - 2 2ε þ 1 2n þ 1

Figure 4. Emission spectra of the compounds in MeOH as a function of water percentage composition: (a) compound I; Curves 1 to 4 correspond to 0%, 20%, 40% and 50% water (v/v), respectively. Inset represents the curves 5 to 7 correspond to 60%, 80% and 100% water (v/v), respectively. (b) compound II; Curves 1 to 7 correspond to 0%, 20%, 40%, 50%, 60%, 80% and 100% water (v/v), respectively.

Figure 5. Plot of emission intensity of compound I against percentage of water (v/v); inset represents the same for compound II.

ε and n are the dielectric constant and refractive index of the medium. The first step of the procedure needs a determination of the contribution of the nonspecific interactions only using the experimentally observed spectral shifts, in both the absorption and emission spectra of the compounds. The results of the solvatochromic study in the hydrocarbon solvents (CYHX and HEP) interacting only nonspecifically correspond to this contribution. The extent of spectral shift by hydrogen bonding interactions (Δvabs shift(H-bond) (H-bond)) can be evaluated from eqs 1 and 2 and the and Δvem shift values are presented in Table 2 abs 2 abs Δvabs shift ðH-bondÞ ¼ vmax ðf ðε, n ÞÞ - vmax

ð1Þ

em 2 em Δvem shift ðH-bondÞ ¼ vmax ðf ðε, n ÞÞ - vmax

ð2Þ

2 2 em where vabs max(f(ε, n )) and vmax(f(ε, n )) are the values of predicted maxima of the absorption and emission spectra of the compounds which correspond to nonspecific interactions only (here HEP). A

glance at the extent of spectral shift shows that the hydrogen bonding interaction is prominent in the ground state for compound II. We also observed the effect on fluorescence emission of the compounds in methanol-water mixtures of different composition in order to rationalize specific solvent-fluorophore interactions, and the spectra are depicted in Figure 4. The addition of water to the methanol solution of compounds I and II changes the fluorescence emission of both compounds, however, in different ways. The fluorescence intensity of the compounds at different percentage composition of methanol-water mixture has been represented by Figure 5. In the case of compound I, addition of water in methanol-water mixture, fluorescence intensity enhances with red shift. It is interesting that water addition (above 50%) to the mixture shows decrease in intensity to some extent. This behavior may be explained by the combined effect of hydrogen bonding and polarity of the medium. Presence of carbonyl oxygen and imide nitrogen allows efficient intermolecular hydrogen bonding interaction with water 2220


The Journal of Physical Chemistry A molecules. As the polarity is increased, the π, π* state (S1) shifts to a lower energy, whereas the n, π* state (S2) shifts to a higher energy, so increasing the gap between the two states which reduces the intersystem crossing from S1 to T146 and an enhancement of fluorescence is observed. This mutual ordering of the π, π* and n, π* takes place up to a certain percentage (50%) of water, and so we may speculate that the relative spacing between these two states reaches maximum at that composition. However, progressive decrement of fluorescence intensity of compound II is observed with a red shift in emission maximum on gradual water addition to the mixture. One possible reason for this behavior could be due to a modification of intermolecular hydrogen bonding interactions between water and the probe molecule by the hydrogen bonded network present in water. As more and more water molecules replace methanol molecules surrounding the fluorophore, the microenvironment around fluorophore consists mainly of associated water clusters owing to the self-aggregation of water molecules. Such types of modified interaction of fluorophore with water molecules in the solvation cell may decrease the hydrogen bonding ability of bare water molecules with fluorophore. Similar hydrogen bonding interaction in other solutes has been observed also in water-aprotic solvent mixtures.52 Excited-State Dipole Moment. Attempts were made to quantify the extent of charge separation on electronic excitation of compounds I and II by measuring the change in the dipole moment (Δμ = μe - μg) utilizing the shift between the absorption and emission maxima (Δv = va - vf) as a function of solvent polarity. According to the Lippert-Mataga equation533 " # 2ðμe - μg Þ2 ε - 1 2n2 - 1 va - vf ¼ þ constant ð3Þ 2ε þ 1 2n2 þ 1 hca3 where Δv is the Stokes shift, μg and μe are ground and excited state dipole moments, c is the velocity of light, h is the Planck’s constant, and a is the Onsager cavity radius swept out by the fluorophore. A plot of Δv versus Δf gives Δμ from the slope. Using the Austin model 1 (AM1), the longest distance between the carbonyl oxygen and C(4) carbon at the napthalimide ring for I and amino nitrogen for II as the Onsager cavity radius (3.47 Å for I and 3.60 Å for II) has been calculated. The dipole moment change on excitation is estimated from the slope of eq 3 to be around 1.17 and 6.99 D for I and II, respectively. From semiempirical molecular orbital calculations at the AM 1 level using the MOPAC program involving complete geometry optimization of the ground state of the fluorophores, the ground state dipole moment (μg) is obtained. Obtained μg for compounds I and II have the values of 5.48 and 7.67 D, respectively. Multiple Linear Regression Analysis. In order to obtain an insight into the various modes of solvation determining the absorption and fluorescence energies, the multiple linear regression analysis approach of Abraham et al.54 has been used. Correlation of E(A) and E(F) were found with Taft’s π* value, an index of the solvent dipolarity/polarizability and the R and β values55 representing the hydrogen bond donating and accepting ability of the solvent, respectively. The following regression equations were obtained for compounds I and II, respectively. For I: EðFÞ ¼ 77:59 - 2:13R - 0:18β - 2:84π EðAÞ ¼ 86:37 - 0:88R þ 1:48β - 2:00π

ARTICLE

For II: EðFÞ ¼ 55:59 - 1:26R þ 1:32β - 2:10π EðAÞ ¼ 72:38 - 1:88R - 5:01β - 3:02π For E(A), the ratio of the regression coefficients of β and R denotes the relative importance of hydrogen bond acceptance over donation by the solvents with the compounds. The ratio is 1.68 for compound I and 2.66 for compound II, indicating that II behaves differently from I due to the presence of electron donating -NH2 group, which induces substantial hydrogen bonding interaction in polar solvents. From the E(F) values, it is observed that the solvent dipolar interaction (π*) and the hydrogen bond accepting property (β) play a pivotal role in the excited state. The ratio indicating the relative importance of π* over β is 15.6 for I and 1.75 for II. This reveals that the dipolar interactions predominate in the excited state properties of I but hydrogen bond formation property predominates in II. The intercept values show the E(A) and E(F) values of the compounds in a purely nonpolar solvent like cyclohexane, where there is no specific interaction. The observed E(F) and E(A) values of I and II in cyclohexane are very close to the intercept values calculated by the multiple linear regression analysis. Free Energy Change of Solvation and Reorganization Energies. A study of free energy change for the process is supposed to provide an empirical measure of the solvation capability of a specified fluorophore. The free energy change of solvation and reorganization energies of both the compounds in various solvents have been estimated (Table 2). According to Marcus56 one can partition E(A) and E(F) as follows EðAÞ ¼ ΔGðsolvÞ þ λ1 EðFÞ ¼ ΔGðsolvÞ - λ0 where, ΔG (solv) is the difference in free energy of the ground state and the equilibrium excited state in a given solvent and λ represents the reorganization energy. Under the condition that, λ0 ≈ λ1 ≈ λ, we get EðAÞ þ EðFÞ ¼ 2ΔGðsolvÞ EðAÞ - EðFÞ ¼ 2λ The ΔG (solv) value of the compounds is maximum for heptane since it is purely nonpolar and also the R and β value of heptane is zero. The ΔG(solv) value is minimum in water. The difference between these values (water and heptane) should give the free energy change required for hydrogen bond formation. The difference in free energy of solvation in heptane and different hydrogen bonding solvents, i.e., Δ(ΔG) (solv) values of the compounds, follow the order of the hydrogen bond energy.57 The reorganization energy values of the compounds were also determined in different solvents. The λ value is maximum in water for compound I and heptane for compound II as expected from solvatochromic studies. Quantum Yield and the Time-Resolved Fluorescence Analysis. Fluorescence quantum yields (Φf) of the compounds were measured in solvents of different polarity and are presented in Table 3. The variation of Φf with solvent polarity parameter ET(30) is depicted at Figure 6. For compound I, Φf rises with increasing polarity of the homogeneous medium but in the case 2221



ARTICLE

Table 3. Fluorescence Quantum Yields, Lifetimes, and Radiative and Nonradiative Rate Constants of the Compounds in Different Solvents Φf solvent

I

kr (ns-1)

τf (ns) II

I

II

I

II

knr (ns-1) I

II

water

0.129

0.128

0.99

3.58

0.130

0.036

0.88

0.24

EG

0.193

0.399

0.67

7.24

0.290

0.055

1.20

0.083

MeOH

0.075

0.388

0.44

7.60

0.170

0.051

2.09

0.08

EtOH

0.059

0.508

0.45

8.84

0.130

0.057

2.07

0.055

ACN DMF

0.038 0.009

0.516 0.680

0.18 0.34

9.82 10.24

0.210 0.028

0.053 0.066

5.28 2.91

0.05 0.03

THF

0.008

0.715

0.37

6.51

0.022

0.109

2.69

0.044

DIOX

0.008

0.771

0.37

10.93

0.021

0.071

2.65

0.021

CYHX

0.002

0.797

0.37

8.12

0.006

0.098

2.70

0.025

HEP

0.002

0.720

0.36

7.44

0.005

0.096

2.73

0.037

Figure 6. Plot of fluorescence quantum yield of compound I as a function of solvent polarity parameter; inset represents the same for compound II.

Figure 7. Typical fluorescence decay curves of compound II associated with lamp profile (a) in different solvents: (b) water; (c) EG; (d) EtOH; (e) DIOX. Excitation wavelength is kept at 403 nm. Inset represents typical fluorescence decay curves of compound I associated with lamp profile in different solvents; excitation wavelength is kept at 370 nm.

of II, Φf decreases with an increase in the polarity of the medium. The reason for the enhanced quantum efficiency of singlet emission of I may be explained as in solvents with polarities and proticities close to ethanol induce inversion between the

Figure 8. Plot of log(knr/kr) of compound II as a function of solvent polarity parameter; inset represents the same for compound I.

singlet (n, π* and π, π*) states without interfering in the triplet manifold.58 As a result, higher fluorescence yields were observed in aqueous solutions than in nonaqueous solvents. On the other hand, in II, the high value of Φf in nonpolar medium may be due to the formation of the ICT state. Hydrogen-bonding interaction is presumably responsible for lowering the Φf values in polar environment. The fluorescence decay behavior of the compounds has been studied in various solvents of different polarity and the data are presented in Table 3. The excited-state decay profiles of the compounds in different homogeneous environment are shown in Figure 7. The full line is the calculated fit assuming an exponential decay convoluted with the instrument response function. Most decay curves of compound II can be well fitted with a single exponential with a χ2 value near unity. In water and THF, the decay behavior is biexponential. Compound II has a higher fluorescence lifetime in aprotic solvents, whereas in protic solvent, the lowering of the decay time is most prominent due to hydrogen bonding interaction. Without putting emphasis on the magnitude of individual decay constants in such biexponential decays, we desire to use the mean fluorescence lifetime (τf) as a valuable parameter for exploring the nature of the interaction. The biexponential fitting does not necessarily indicate that the decay curve has only two discrete time constants; it may imply a distribution of time constants around two well-separated values, and one may speculate that the compounds experiences two different local conformations resulting from the hydrogen bonding interaction between the compound and the solvents. The effect of polarity on fluorescence lifetime is very similar to what is observed for the fluorescence quantum yield. Increase in the polarity of the medium leads to shortening of the lifetime. The fluorescence lifetime of compound I in water was found to be 0.99 ns. In hydrocarbon solvents, the lifetime is even shorter. Compared to compound I, compound II shows a substantial increase in its fluorescence lifetime values in different solvents. The presence of electron donating -NH2 moiety in II assists considerable increase in charge separation in the compound leading to a dramatic enhancement in the ICT process. The effect is more prominent in polar aprotic solvents where the ICT process predominates over the hydrogen bonding effect. Radiative and Nonradiative Rate Constant. To investigate the effect of solvation on the dynamics of the excited state the radiative (kr = Φf /τf) and nonradiative (knr = (1 - Φf)/τf) rate constants were calculated by using fluorescence quantum yields 2222


The Journal of Physical Chemistry A Scheme 3. Schematic Representation of the Probable Hydrogen Bonded Cage Structure in Water: (a) for Compound I and (b) for Compound II

(Φf) and lifetimes (τf) of the compounds in different solvents. The values of kr and knr in different solvents are presented in Table 3. Figure 8 shows the variation of log(knr/kr) with solvent polarity parameter (ET(30)) for I and II, respectively. It is observed that with increasing ET(30) values of the solvents, log(knr/kr) of compound II increased gradually. Thus, with increasing solvent polarity, compound II is getting involved in the hydrogen bond formation with the solvents. This corroborates the fact that the hydrogen bonded structure of compound II dissipates energy via nonradiative manner. Surprisingly, log(knr/ kr) for compound I diminishes with increasing polarity of the medium. This interesting fact corroborates that the photophysical response of these compounds in a homogeneous environment depends on the polarity and the ability to form a hydrogen bond with the solvents, which generates the solvent cage environment of the solute molecules.59 This observed fact may be due to the hydrogen bonded structure of I in the polar protic solvents gaining sufficient rigidity to retard the process of energy deactivation via nonradiative pathways. A schematic mechanism is proposed that involves the formation of a hydrogen bonded solvent cage which is responsible for such behavior (Scheme 3). The water molecules get attached between adjacent carbonyl oxygen and imide nitrogen and formed a rigid water cluster. So, a nonradiative decay process is greatly reduced due to formation of a rigid framework. In compound II having an -NH2 group attached at the C(4) position of the naphthalimide ring distributed excitation energy via vibronic coupling through hydrogen bonding. Time-Dependent (TD)-DFT Calculations. Quantum chemical calculations based on density functional theory (DFT) were performed in order to understand the energy levels and to explain the transitions of observed absorption and emission spectra of compounds I and II. The optimized gas phase ground-state geometry of the compounds using method B3LYP at basis set 6-31G* is obtained and is shown in the scheme. The calculated ground-state dipole moment for compound I is 5.08 D whereas for

ARTICLE

Scheme 4. Frontier Orbitals of Compounds I and II Calculated by the B3LYP/6-31G* TD-DFT Method on Excited State

compound II, presence of an amino group induces the generation of a charge transfer state resulting in a dipole of 8.77 D. Timedependent DFT (TD-DFT) calculation yields the first vertical transition S1 to S0 of I and II, a HOMO to LUMO excitation at wavelength 323 and 368 nm with oscillator strengths of 0.1907 and 0.2033, respectively. On the basis of the one electron LUMO and HOMO characteristics, this transition involves the n and π electrons on the nitrogen atom and naphthalene plane to the π* orbital in the isoquinolinedione moiety. The isodensity surface plots of HOMO and LUMO are shown in Scheme 4. The electronic distribution in HOMO performed on the optimized geometry of compound I by the DFT method shows that there is more electron density on the naphthalene rings on the left compared to that on the imide ring on the right. LUMO electron density of I shows that the electron cloud shifts more toward the imide ring on the right and the electron density on oxygen atoms increases in LUMO compared to that in HOMO. It predicts more electron density on the oxygen atom than on the imide nitrogen in LUMO which facilitates charge transfer from imide nitrogen to the oxygen atom. In II, most of the HOMO is delocalized on amino group and naphthalene ring. LUMO electron density of II shows that the electron cloud of the amino nitrogen largely shifts toward the imide ring as well as on the oxygen atom of the carbonyl group. Energy of the frontier HOMO and LUMO orbital of compound I is -0.2447 and -0.0849 eV while that of compound II is -0.2123 and -0.0761 eV, respectively.

’ CONCLUSIONS In summary, several interesting aspects of the photophysical properties of two newly synthesized pharmaceutically important naphthalimide derivatives have been described and the utilities of the fluorescence responses of these molecules in obtaining information on the structural change in the ground state as well as in the excited state with polarity of the microenvironment have been pointed out. Incorporation of an amino group at the C(4) position of the naphthalimide ring leads to considerable changes in the spectral response and fluorescence efficiency of the systems in comparison with the unsubstituted analogue. The effect may be ascribed mainly to the lowering of the singlet 2223


The Journal of Physical Chemistry A excited state and change in the relative energy of the π, π* and n, π* states with respect to the triplet energy of the same manifold. In the case of compound II, interplay occurs between ICT and hydrogen bonding interactions in aprotic polar and protic polar media, respectively, whereas in compound I, the intermolecular hydrogen bonding plays a prominent role. The theoretical results based on density functional theory are in good agreement with experimental data. The nonradiative energy of compound I decreases gradually with increase in solvent polarity which can be attributed to formation of rigid solvation cage due to hydrogen bonding. Conversely, the observed decrease in the fluorescence quantum yields and lifetimes of compound II in protic solvents occurs via vibronic coupling through hydrogen bonding. The photophysical signature of these bioactive naphthalimide derivatives in a homogeneous environment is a step toward a more extensive application in research fields of current interests, i.e., assessment and elucidation of the transport mechanism of a drug to the target molecule.

’ AUTHOR INFORMATION Corresponding Author

*E-mail: [email protected] or scbhattacharyya@chemistry. jdvu.ac.in.

’ ACKNOWLEDGMENT One of the authors S.D. acknowledges UGC for the research fellowship. A grant from CSIR, Government of India, is gratefully acknowledged. S.B. wishes to thank the Director of CNCI for support. ’ REFERENCES (1) Hashimoto, M.; Hamaguchi, H. J. Phys. Chem. 1995, 99, 7875. (2) Grabowski, Z. R. Pure Appl. Chem. 1993, 65, 1751. (3) Marcus, R. A. Rev. Mod. Phys. 1993, 65, 599and references therein.. (4) Wang, S. L.; Ho, T. I. J. Photochem. Photobiol., A 2000, 135, 119. (5) Braun, D.; Retting, W.; Delmond, S.; Letard, J. F.; Lapouyade, R. J. Phys. Chem. A 1997, 101, 6836. (6) Lueck, H.; Windsor, M. W.; Rettig, W. J. Phys. Chem. 1990, 94, 4550. (7) EI-Kemary, M. A. J. Photochem. Photobiol., A 2000, 137, 9. (8) Oevering, H.; Verhoeven, J. W.; Paddon-Row, M. N.; Warman, J. M. Tetrahedron 1989, 45, 4751. (9) Verhoeven, J. W. Pure Appl. Chem. 1990, 62, 1585. (10) Al-Ansari, I. A. Z. J. Phys. Org. Chem. 1997, 10, 687. (11) Wang, P.; Wu, S. J. Photochem. Photobiol., A 1994, 77, 127. (12) Raju, B. B.; Varadarajan, T. S. J. Photochem. Photobiol., A 1995, 85, 263. (13) Turro, N. J. Modern Molecular photochemistry; Benjamin/Cummings: Menlo Park, CA, 1978. (14) Mataga, N.; Kubota, T. Molecular interactions and Electronic Spectra; Dekker: New York, 1970, Chapter 7, p 8. (15) Lim, E. C. J. Phys. Chem. 1986, 90, 6770. (16) van der Burgt, M. J.; Jansen, L. M. G.; Huizer, A. H.; Varma, C. A. Z. O. Chem. Phys. 1995, 201, 525. (17) Bailly, C.; Carrasco, C.; Joubert, A.; Bal, C.; Wattez, N.; Hildebrand, M. P.; Lansiaux, A.; Colson, P.; Houssier, C.; Cacho, M.; Ramos, A.; Bra~na, M. F. Biochemistry 2003, 42, 4136and references therein.. (18) Bra~na, M. F.; Ramos, A. Curr. Med. Chem.: Anti-Cancer Agents 2001, 1, 237. (19) Malviya, V. K.; Liu, P. Y.; Alberts, D. S.; Surwit, E. A.; Craig, J. B.; Hanningan, E. V. Am. J. Clin. Oncol. 1992, 15, 41. (20) Liu, Z.; Hecker, K. H.; Rill, R. L. J. Biomol. Struct. Dyn. 1996, 14, 331.

ARTICLE

(21) Rogers, J. E.; Kelly, L. A. J. Am. Chem. Soc. 1999, 121, 3854. (22) Chanh, T. C.; Lewis, D. E.; Judy, M. M.; Bernal, F. S. Michalek, G. R.; Utecht, R. E.; Skiles, H.; Chang, S. C.; Matthews, J. L. Antiviral Res. 1994, 25, 133. (23) Middleton, R. W.; Parrick, J. J. Heterocycl. Chem. 1985, 22, 1567. (24) Saito, I.; Takayama, M.; Kawanishi, S. J. Am. Chem. Soc. 1995, 117, 5590. (25) Alexiou, M. S.; Tychopoulos, V.; Ghorbanian, S.; Tyman, J. H. P.; Brown, R. G.; Brittain, P. I. J. Chem. Soc., Perkin Trans. 1990, 2, 837. (26) Magalh~aes, J. L.; Pereira, R. V.; Triboni, E. R.; Berci Filho, P.; Gehlen, M. H.; Nart, F. C. J. Photochem. Photobiol., A 2006, 183, 165. (27) Patrick, L. G. F.; Whiting, A. Dyes Pigm. 2002, 52, 137. (28) Martin, E.; Weigand, R.; Pardo, A. J. Lumin. 1996, 68, 157. (29) Tao, Z. F.; Qian, X. Dyes Pigm. 1999, 43, 139. (30) Stewart, W. J. Am. Chem. Soc. 1981, 103, 7615. (31) de Souza, M. M.; Correa, R.; Filho, V. C.; Grabchev, I.; Bojinov, V. Pharmazie 2002, 56, 430. (32) Bouche, C. M.; Berdague, P.; Facoetti, H.; Robin, P.; Le Barny, P.; Schott, M. Synth. Met. 1996, 81, 191. (33) Tian, H.; Gan, J.; Chen, K.; He, J.; Song, Q.; Hou, X. J. Mater. Chem. 2002, 12, 1262. (34) Gunnlaugsson, T.; McCoy, C.; Morrow, R.; Phelan, C. Stomeo, F. ARKIVOC 2003, 7, 216. (35) Zhu, W.; Hu, M.; Yao, R.; Tian, H. J. Photochem. Photobiol., A 2003, 154, 169. (36) Grabchev, I.; Moneva, I.; Wolarz, E.; Bauman, D. Z. Naturforsch. 1996, 51a, 1185. (37) Cosnard, F.; Wintgens, V. Tetrahedron Lett. 1998, 39, 2751. (38) Hossain, Sk. U.; Sengupta, S.; Bhattacharya, S. Bioorg. Med. Chem. 2005, 13, 5750. (39) Vogel, A. I. Textbook of Practical Organic Chemistry, 5th ed.; Singapore Publishers Ltd.: Singapore, 1994; pp 397-403. (40) Morris, J. V.; Mahaney, M. A.; Huber, J. R. J. Phys. Chem. 1976, 80, 969. (41) Barros, T. C.; Molinari, G. R.; Berci Filho, P.; Toscano, V. G.; Politi, M. J. J. Photochem. Photobiol., A 1993, 76, 55. (42) Ghosh, S. K.; Hossain, Sk. U.; Bhattacharya, S.; Bhattacharya, S. C. J. Photochem. Photobiol., B 2005, 81, 121. (43) Yuan, D. W.; Brown, R. G. J. Phys. Chem. A 1997, 101, 3461. (44) Saha, S.; Samanta, A. J. Phys. Chem. A 2002, 106, 4763. (45) Elbert, J. E.; Paulsen, S.; Robinson, L.; Elzey, S.; Klein, K. J. Photochem. Photobiol., A 2005, 169, 9. (46) Samanta, A.; Saroja, G. J. Photochem. Photobiol., A 1994, 84, 19. (47) Lim, E. C. In Excited States; Lim, E. C., Ed.; Academic: New York, 1977; Vol. 3. (48) Lai, T.; Lim, E. C. J. Am. Chem. Soc. 1985, 107, 1134. (49) Ramachandram, B.; Samanta, A. Chem. Commun. 1997, 1037. (50) Reichardt, C. Solvents and Solvent Effects in Organic Chemistry, 2nd ed.; VCH: Weinheim, 1988. (51) Krystkowiak, E.; Dobek, K.; Maciejewski, A. J. Photochem. Photobiol., A 2006, 184, 250. (52) Chatterjee, S.; Banerjee, P.; Pramanik, S.; Mukherjee, A.; Mahalanabis, K. K.; Bhattacharya, S. C. Chem. Phys. Lett. 2007, 440, 313. (53) Pramanik, S.; Banerjee, P.; Sarkar, A.; Mukherjee, A.; Mahalanabis, K. K.; Bhattacharya, S. C. Spectrochim. Acta, Part A 2008, 71, 1327. (54) Abraham, M. H.; Greillier, P. L.; Abboud, J. L. M.; Doherty, R. M.; Taft, R. W. Can. J. Chem. 1988, 66, 2673. (55) Kamlet, M. J.; Abboud, J. L. M.; Abraham, M. H.; Taft, R. W. J. Org. Chem. 1983, 48, 2877. (56) Marcus, R. A. J. Chem. Phys. 1963, 38, 1858. (57) Castellan, G. W. Physical Chemistry, 3rd ed.; Narosa Publishing House: Delhi, 1985. (58) Berci Fo, P.; Toscano, V. G.; Politi, M. J. J. Photochem. Photobiol., A 1988, 43, 51. (59) Coronado, J. L. Gu.; Martı’n, E.; Montero, L. A.; Fierro, J. L. G.; García de la Vega, J. M. J. Phys. Chem. A 2007, 111, 9724.

2224


Tunable Solvatochromic Response of Newly Synthesized

Recommend Documents