One-pot synthesis of functionalized 4-hydroxy-3-thiomethylcoumarins: detection and discrimination of Co²⁺ and Ni²⁺ ions

Abstract

A wide variety of 4-hydroxy-3-thiomethylcoumarin derivatives were synthesized through a one-pot three-component reaction from 4-hydroxycoumarin, aldehydes and thiols, catalysed by L-proline in ethanol at room temperature, in moderate to good yields. The present protocol offers many advantages such as milder reaction conditions, green solvent, easy work up procedure and requirement of a smaller amount of catalyst. Furthermore, one of the derivatives (30a) has been successfully employed as a “turn-off” fluorescence probe that displays remarkable changes in its optical properties only in the presence of cobalt and nickel ions in aqueous based media. The ligand (30a) showed high selectivity towards Co²⁺ & Ni²⁺ without any interference from other commonly coexisting metal ions. Fluorescence quenching of ligand (30a) by Co²⁺ & Ni²⁺ was found to be ∼80% and ∼85% respectively in 9 : 1 DMSO/HEPES buffer (pH = 7.4, 10 mM) at room temperature. Significant changes in the UV-vis spectra with a clear formation of isosbestic points confirms the formation of ligand–metal complexes. The predicted binding mode (2 : 1) for ligand–metal was observed from High Resolution Mass Spectroscopy, Job's plots and single crystal X-ray structures of the complexes. The lower stability of the cobalt(II) complex than the nickel(II) complex provides a reliable platform to distinguish Co²⁺ from Ni²⁺ via a “turn-on” photoluminescence response towards the disodium salt of ethylenediaminetetraacetic acid (EDTA).

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Introduction

Among various substituted coumarins, 3-substituted 4-hydroxycoumarin represents one of the most active classes of compounds possessing a wide spectrum of biological activity and medicinal utility.¹ 3-Benzyl substituted 4-hydroxycoumarin derivatives are constituents of various natural products like warfarin, phenprocoumon, coumatetralyl, bromadiolone etc. 4-Hydroxycoumarin derivatives have been widely used for curing myocardial infarction, strokes and venous thromboembolism.² These compounds are recognized to possess biological and pharmaceutical activities, such as anti-inflammatory, antithrombotic, anticoagulant, antioxidant, antibacterial, anthelminthic and anti-HIV activities.³ 4-Hydroxycoumarin derivatives also act as inhibitors of NAD(P)H:quinone oxidoreductase-1 (NQO1),⁴ antagonize vitamin K epoxide reductase (VKOR) or proteins induced by vitamin K antagonism (PIVKA-II),⁵ that shows the metalloenzyme carbonic anhydrase (CA) inhibitory activity,⁶ potential anti-acetylcholinesterase (AChE) inhibitors as therapeutics for Alzheimer's disease.⁷

Coumarin derived molecules also act as promising fluorescent probes⁸ due to their excellent photophysical properties. Several coumarin derived molecules have been reported for selective and sensitive determination of transition metal ions.⁹ However, less attention has been paid in designing coumarin based probes for selective detection of cobalt and nickel due to interference from other metals. Cobalt and nickel are considered as essential micronutrients for both plants as well as animals. Cobalt is generally found in cobalamins¹⁰ and act as a metal cofactor of Vitamin B₁₂. Apart from biological importance in several body metabolisms, its exposure at high levels can cause severe health problems¹¹ viz. mutagenesis, cardio-toxicity, asthma, lung-fibrosis, elevation of blood cells and allergic contact dermatitis. Nickel has wide range of applications such as in Ni–Cd batteries, electroplating, pigments for paints, ceramics, catalysts for hydrogenation and in electronic industries. In excess, it is also responsible for several diseases¹² related to the respiratory and central nervous system. These metal ions can be easily contaminated in the environment¹³ via burning of coal and oil, truck and aircraft exhausts, diamond polishing, porcelain, volcanic eruptions and chemical industries. Thus, the development of highly sensitive probes to monitor the presence of these metals in industrial, environmental and food samples for maintaining good human health is of immense significance.

In recent years, several techniques¹⁴ such as atomic absorption spectrometry (AAS), atomic absorption spectrometry-electro thermal atomization (AAS-ETA), inductively coupled plasma atomic emission spectroscopy (ICP-AES) and flame photometry have been employed for the determination of heavy metals. These methods provide precise outcomes but are not applicable for the analysis of a large number of environmental samples as they require appropriate expertise and good infrastructure. Fluorescence based sensors appear as excellent materials for chemical sensing due to high signal response.¹⁵ However, very few sensors have been reported¹⁶ based on fluorometric method for the selective detection of Co²⁺ and Ni²⁺. Many of these existing systems have several limitations in their applicability, owing to lengthy synthetic approach, low sensitivity, use of large amount of toxic solvents and interference with other metals. Therefore, design and development of suitable fluorescent probe for Co²⁺ and Ni²⁺ with high sensitivity and selectivity is still a challenging task.

Recently, we have shown the utility of 4-hydroxycoumarin as key starting material for construction of annulated pyran¹⁷ and dihydrochromeno[4,3-b]pyrazolo[4,3-e]pyridin-6(7H)-ones heterocycles through multicomponent reactions (MCRs).¹⁸ It has also been explored by others for the synthesis of chromene derivatives,¹⁹ coumestan derivatives,²⁰ pyrrolizinone²¹ and important synthetic intermediates.²² We have realised that a wide variety of 4-hydroxy-3-thiomethylcoumarin derivatives can be constructed at the expanse of 4-hydroxycoumarin, aldehydes and thiols under milder reaction conditions. Although few indirect examples of 4-hydroxy-3-thiomethylcoumarin derivative are reported but are not fully explored.²³

L-Proline, an amino acid, has been exploited as an effective bifunctional chiral organocatalyst and it enabled a variety of organic reactions to undergo, either by acting as an acid or base. It is quite similar to enzymatic catalysis.²⁴ It has been smartly used to catalyze various reactions viz. Knoevenagel, Mannich and Michael reactions by the activation of carbonyl group through enamine–iminium ion intermediate formation.²⁵ Our group has remarkable attributes in MCRs, in which organocatalyst acts as a key intermediate for the synthesis of sulfur containing compounds.²⁶ As a part of an ongoing research project on MCRs for the synthesis of sulfur containing compounds,²⁷ we conceived that L-proline could be used as an efficient catalyst for the synthesis of substituted 4-hydroxy-3-thiomethylcoumarins. The syntheses of these compounds may be useful for studying their biological activity in the near future.

Herein, we have developed a selective C-3 alkylation based on a three-component strategy involved via a domino process comprising a Knoevenagel type condensation between 4-hydroxycoumarin and aldehyde, followed by a thia-Michael addition onto the resulting unsaturated ketone and generation of 4-hydroxy-3-thiomethylcoumarin derivatives (Scheme 1). Furthermore, the compound 30a displays a remarkable change in its optical properties only in the presence of cobalt and nickel in aqueous based media. The probe is based on fluorescence “turn-off” strategy and the binding of these two metals with compound 30a forms non-fluorescent complexes, confirmed via single crystal X-ray structures. Moreover, the two metals can be distinguished by EDTA induced fluorescence recovery that was only possible towards cobalt(II) complex. This unique yet simple strategy for metal detection is rare and serves as an efficient probe for the detection and discrimination of cobalt and nickel metals.

Scheme 1 Synthesis of 3-(alkyl/aryl(alkyl/arylthio)methyl) substituted 4-hydroxy coumarins.

Results and discussion

Synthesis of 4-hydroxycoumarin derivatives

Initially, to achieve 4-hydroxy-3-thiomethylcoumarin derivative we conducted a one-pot reaction with 4-hydroxycoumarin, benzaldehyde and ethanethiol in 3 mL of ethanol at room temperature in the absence of catalyst (Table 1, entry 1). However, no product was obtained. Then the same reaction was carried out with L-proline as catalyst with different catalyst loading as shown in Table 1 (entries 2–5). It was found that 10 mol% of the catalyst provides 83% yield (Table 1, entry 3). Further increase in the amount of the catalyst did not improve the yield of product significantly. Other catalysts such as triethylamine (Et₃N), p-toluenesulfonic acid (p-TsOH), ferric sulfate (Fe₂(SO₄)₃), iodine (I₂), and tetrabutylammonium bromide (TBAB) were also used, however, the desired product was obtained in lower yield (Table 1, entries 6–10). In order to improve the yield of the product further, we screened the reaction with different solvents like acetonitrile, methanol, dichloroethane, dichloromethane and dimethylsulfoxide, using 10 mol% of L-proline (Table 1, entries 11–15). However, no increment in the yield was observed. Hence, 10 mol% of L-proline in ethanol was found to be the optimized reaction condition. In addition, it is noteworthy to mention here that the sequence of addition of aldehyde, catalyst and coumarin as well as a fast addition of thiol after addition of coumarin to the reaction mixture are very important facts in this reaction as coumarin has a tendency to form biscoumarin derivatives in the presence of aldehyde.

Table 1 Optimization of reaction conditions^a

Entry	Catalyst (mol%)	Solvent	Time (h)	Yield^b (%)
a Reaction conditions: 4-hydroxycoumarin (1 mmol), benzaldehyde (1 mmol), ethanethiol (1.2 mmol), at room temperature.b Isolated yield.c No product was formed.
1	No catalyst	C2H5OH	12	—^c
2	Proline (5)	C2H5OH	7.0	40
3	Proline (10)	C2H5OH	3.0	83
4	Proline (15)	C2H5OH	3.0	84
5	Proline (20)	C2H5OH	3.0	86
6	Et3N (10)	C2H5OH	6.0	35
7	p-TsOH (10)	C2H5OH	5.0	45
8	Fe2(SO4)3 (10)	C2H5OH	5.0	40
9	I2 (10)	C2H5OH	6.0	42
10	TBAB (10)	C2H5OH	7.0	38
11	Proline (10)	CH3CN	3.0	69
12	Proline (10)	CH3OH	3.0	73
13	Proline (10)	C2H4Cl2	3.0	65
14	Proline (10)	CH2Cl2	3.0	60
15	Proline (10)	DMSO	3.0	67

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Having the optimized conditions at hand, the substrate scope of the protocol was scrutinized (Table 2). In this mission, the effects of substituents on the thiols and aldehydes were investigated under the optimized reaction conditions. Initially 4-hydroxycoumarin (1) and benzaldehyde (2) were treated with a series of aliphatic thiols (3) to observe the reactivity of different thiols (Compounds 1a–5a). Ethyl, propyl, benzylthiol and 2-chlorobenzylthiol produced the desired products in comparable yields (Compounds 1a–4a), however, the yield decreased in case of 2-mercaptoethanol (Compound 5a). After examining the aliphatic thiols, we turned out attention towards aromatic thiols keeping all other reactants unaltered.

Table 2 Synthesis of 4-hydroxy-3-thiomethylcoumarins^a,b

a Reaction conditions: 4-hydroxycoumarin (1 mmol), aldehyde (1 mmol), thiol (1.2 mmol), using L-proline as a catalyst in ethanol (3 mL) at room temperature.b Isolated yield.

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We used unsubstituted aromatic thiols as well as thiols with electron donating and withdrawing substituents (Compounds 6a–10a). In all the cases we got similar yield of the expected products, however, thiol with electron donating functionality reacts little faster than the electron withdrawing counterparts. 2-Naphthalenethiol also underwent the transformation smoothly to produce the expected product in good yield (Compound 11a). After observing the effect of different thiols, we focused our attention towards examining the effect of substituents on the aldehyde on the outcome of the reaction. Initially, we used thiophenol and various aromatic and aliphatic aldehydes (Compounds 12a–15a). Here, the aromatic aldehydes produced better yields than the aliphatic aldehydes that may be due to the relative instability of aliphatic aldehydes. Next, we inspected the effect of substituents on aromatic aldehyde in the reaction with 4-hydroxycoumarin and p-tolylthiol (Compounds 16a–25a). It was observed that the electronic factor of the substituents on the aldehyde does not play much prominent role, however, the steric factor does. Hence, the p-substituted derivatives produced better yields (Compounds 16a–22a) than the o-substituted derivatives (Compounds 23a and 24a). Moreover, it was found that 2,4-dimethoxybenzaldehyde also produced the desired product with good yield (Compound 25a). Notably, 2-naphthaldehyde also reacted smoothly to produce the desired product in good yield (Compound 26a). In the presence of 4-halo substituted thiols, 4-methoxy and 4-cyanobenzaldehyde reacts with similar efficiency (Compounds 27a and 28a), although the yield was slightly higher in the latter case. Heterocyclic aldehydes also worked well to produce the desired products in good yield (Compounds 29a and 30a).

Plausible mechanism

The reaction of 4-hydroxycoumarin with aromatic aldehyde gives Knoevenagel intermediate in presence of L-proline catalyst. We believe that L-proline activates the aromatic aldehyde which can assist the formation of Knoevenagel intermediate with the 4-hydroxycoumarin through Knoevenagel condensation. The nucleophilic addition to Knoevenagel intermediate via conjugate addition to α,β-unsaturated carbonyl group by substituted thiols provides the final product (Scheme 2).

Scheme 2 Plausible reaction mechanism.

The present protocol works with various thiols as well as with different aliphatic and aromatic aldehydes. All the isolated products were fully characterized by IR, HRMS, ¹H NMR, and ¹³C NMR spectroscopy. Moreover, the structure of compound 28a was further confirmed by the X-ray crystallographic analysis (Fig. 1/S9†).

Fig. 1 Single-crystal X-ray structure of 28a.

The packing diagram of 28a exhibits short S1⋯O2 (3.253 Å) intra-hetero-atomic contacts within the molecule and intermolecular interaction between O1⋯O2 (2.650 Å) to form the long chain structure (Fig. S1a†). The packing diagram of 28a also shows π⋯π stacking interaction C10–C15⋯C10–C15 (3.554 Å) between the aromatic rings of two polymeric chain units, which are running anti-parallel to each other leads to the formation of ladder like structure. These polymeric chains are interlinked in anti-fashion via intermolecular C–H⋯π interaction C13H13⋯C1–C6 (2.578 Å) to form 2D double stranded sheet structure. Furthermore, the two separate 2D double stranded sheet structures are interlinked by intermolecular interaction between S1⋯H19 (2.998 Å) (Fig. S1b†). For clarity, the above interactions are presented collectively as given in ESI file (Fig. S1c and d†). In the last few years, these non-covalent interactions involving aromatic rings such as π⋯π, C–H⋯π interactions have lured researchers from the field of pharmaceutical, optical, and functional materials.²⁸ It can also find a wide application in biological systems.²⁹

Photophysical studies

Ligand 30a was chosen as model compound for sensing studies due to the presence of electron donating nitrogen atom (pyridine ring) unlike other compounds. Considering limited water solubility, the photophysical properties of 30a was studied in DMSO/HEPES buffer (9 : 1, pH = 7.4) mixture via UV-vis and fluorescence spectroscopy. The newly synthesized ligand 30a showed two characteristic bands at 254 nm and 313 nm in UV-vis spectrum with an emission maximum at 401 nm (320 nm excitation), respectively. Fluorescence quenching experiment was performed by adding aliquots of Co²⁺ and Ni²⁺ separately to the solution of 30a (25 μM) in DMSO/HEPES buffer (9 : 1, pH = 7.4). The fluorescence intensity decreases gradually with the increasing concentration of Co²⁺ and Ni²⁺ (Fig. 2a and b), ∼80% and ∼85% fluorescence quenching was observed at concentration of 16.6 μM Co²⁺ and 10 μM Ni²⁺, respectively. The quenching constant values obtained via linear fitting of S–V plot for Co²⁺ and Ni²⁺ (Fig. S2a and b†) were found to be 1 × 10⁵ M⁻¹ and 2.4 × 10⁵ M⁻¹ respectively, indicating very high quenching efficiencies. The LOD value was observed to be as low as 0.22 and 0.13 μM for Co²⁺ and Ni²⁺ (Fig. S3a and b†) confirming the practicability of the system for real sample analysis.

Fig. 2 Emission spectra of 30a (25 μM) with varying concentration of (a) Co²⁺ and (b) Ni²⁺ in DMSO/HEPES buffer (9 : 1, pH = 7.4) at room temperature.

The quenching of fluorescence can be attributed to the deprotonation of –OH group attached to the ligand (30a) on addition of Co²⁺ or Ni²⁺ that consequently affects the electronic properties of the fluorophore via intermolecular charge transfer (ICT) between the metal and the ligand. To evaluate the selectivity, ligand (30a) was treated with various common metal ions including alkali and transition metal ions viz. Na⁺, Ca²⁺, K⁺, Pb²⁺, Ag⁺, Mn²⁺, Cr³⁺, Al³⁺, Fe³⁺, Fe²⁺ and Hg²⁺ (Fig. 3 and S4†). Interestingly, these metal ions do not affect the fluorescence spectra of 30a when excited at 320 nm. Thus, the probe was found to be highly selective and sensitive towards Co²⁺ and Ni²⁺ ions only.

Fig. 3 Effect of various metal ions on emission of 30a in DMSO/HEPES buffer (9 : 1, pH = 7.4). Concentration of 30a and metal ions were 25 μM and 20 μM, respectively.

Binding studies via Job plot, ESI-HRMS and UV-visible spectroscopy

Job's Plot¹⁰ analysis confirms the 2 : 1 stoichiometry for the host–guest complexation. The summation of the concentration of ligand 30a and Co²⁺ was kept constant as 25 μM, and the fluorescence intensity of ligand 30a with Co²⁺ in four different concentrations (2 μM, 4 μM, 6 μM, 8 μM) was observed as shown in Fig. 4a. The linear fitting analysis demonstrated that the concentration of Co²⁺ was ∼8 μM when the fluorescence of ligand was almost quenched, suggesting the probable binding for ligand–metal as 2 : 1 stoichiometry. Similar binding ratio was also observed for ligand 30a and Ni²⁺ suggesting 2 : 1 stoichiometry (Fig. 4b).

Fig. 4 Job's plot analysis of the stoichiometry of ligand 30a with (a) [Co²⁺] and (b) [Ni²⁺] in DMSO/HEPES buffer (9 : 1, pH = 7.4) (excited at 320 nm).

The High Resolution Mass Spectroscopy (HRMS) spectra of a mixture of ligand 30a with Ni²⁺/Co²⁺ also justify the formation of a 2 : 1 ligand–metal complex with a major signal at m/z = 684.0793 for 30a-Co²⁺ and m/z = 683.0815 for 30a-Ni²⁺ (Fig. S5 and S6†). The binding constant^16c of ligand 30a for cobalt and nickel via nonlinear least squares analysis was observed to be 9.3 × 10⁴ M⁻¹ and 2.07 × 10⁵ M⁻¹, respectively (Fig. S7a and b†).

A control study using compound 1a was also performed to confirm whether the presence of adjacent pyridinium nitrogen in 30a is necessary to form a complex with cobalt or nickel. Fluorescence titration experiment of 1a with Co²⁺ or Ni²⁺ showed no change in fluorescence emission (Fig. S8†). Hence, it can be concluded that nitrogen present on adjacent group actively takes part in complexation process viz-a-viz quenching process.

Titration of 30a with Co²⁺ and Ni²⁺ was also observed by UV-vis spectroscopy (Fig. 5a and b). On adding Co²⁺ to the solution of 30a (25 μM) in 9 : 1 DMSO/HEPES, the absorption maximum peak of 30a at 313 nm was significantly decreased and the peak at 254 nm was enhanced with the clear formation of an isosbestic point at around 304 nm. Similar observation was observed on adding Ni²⁺ to the solution of 30a with an isosbestic point at 303 nm. Changes in absorbance and formation of isosbestic points are strong evidence for the formation of stable complex between the ligand and these metals.

Fig. 5 UV-visible titration spectra of 30a (25 μM) against various concentration of (a) Co²⁺ (5 μM) and (b) Ni²⁺ (3 μM) in DMSO/HEPES buffer (9 : 1, pH = 7.4) at room temperature.

Crystallographic studies

Finally, the predicted binding mode of ligand 30a with cobalt and nickel was confirmed by single crystal X-ray structure of the complexes (Fig. 6a/S10† and Fig. 6b/S11†) obtained in dichloromethane–methanol solution as determined by the X-ray diffraction method (Table S2†). It was observed that two ligand units bind with single Co²⁺/Ni²⁺ atom via six coordination bonds.

Fig. 6 The X-ray crystal structures of (a) cobalt(II) complex and (b) nickel(II) complex.

Discrimination between cobalt and nickel

In order to differentiate cobalt and nickel, a strong chelating agent disodium salt of ethylenediaminetetraacetic acid (EDTA) was employed which is reported^16b,30 to have good affinity for Co²⁺ compared to Ni²⁺. The cobalt(II) complex displayed “turn-on” fluorescence response towards EDTA due to the displacement of metal from the complex with the total fluorescence recovery of ∼80% on addition of total 1.1 eq. EDTA (Fig. 7a). However, nickel(II) complex did not show any significant change (Fig. 7b) in fluorescence on adding EDTA even after prolonged time of 30 minutes. These results demonstrate the method as simple and rapid to discriminate Co²⁺ from Ni²⁺ using displacement mechanism.

Fig. 7 Photoluminescence spectra of (a) cobalt(II) complex and (b) nickel(II) complex on addition of EDTA.

Conclusions

In conclusion, a convenient and environmentally green methodology for the synthesis of 3-(alkyl/aryl(alkyl/arylthio)-methyl) substituted 4-hydroxycoumarin derivatives via the three-component reactions of 4-hydroxycoumarin, aldehydes, and thiols by using L-proline as efficient catalyst at room temperature has been developed. The attractive features of this protocol are simple reaction procedure, short reaction time, high yield and easy isolation technique of the product, its flexibility for the synthesis of a broad range of 3-(alkyl/aryl(alkyl/arylthio)methyl) substituted 4-hydroxycoumarin derivatives in moderate to high yields. Additionally, the demonstration of 28a crystal structure, towards non-covalent interactions is expected to make a significant impact among the researchers working in the area of supra-molecular chemistry, sensing applications for environmental contaminants and biologically relevant ions. Furthermore, sensing studies performed using model compound 30a suggests that the ligand can be used as an effective fluorescence tool to monitor and distinguish traces of both cobalt and nickel in the competent environment.

Experimental

Material and instruments

All the reagents were of analytical reagent (AR) grade and were used as purchased without further purification. Melting points were recorded in an open capillary tube and are uncorrected. Fourier transform infrared (FT-IR) spectra were recorded as neat liquid or KBr pellets. ¹H and ¹³C NMR spectra were recorded on Varian 400 MHz NMR spectrometer TMS as internal reference; chemical shifts (δ scale) are reported in parts per million (ppm). ¹H NMR Spectra are reported in the order: multiplicity, coupling constant (J value) in hertz (Hz) and no. of protons; signals were characterized as s (singlet), d (doublet), dd (doublet of doublets), t (triplet), m (multiplet). Mass spectra were recorded using ESI/APCI mode (Q-TOF type Mass Analyzer). Column chromatographic separations were performed using silica gel (60–120 mesh). Metal salts were used as their perchlorates. HPLC grade DMSO and Milli-Q water was used in all the experiments. UV-visible absorption spectra were obtained using a Perkin-Elmer Lambda 25 spectrophotometer. Fluorescence emission spectra were recorded on Horiba Fluoromax-4 spectrofluorometer using 10 mm path length quartz cuvette and a slit width of 3 nm at room temperature. The X-ray crystal structures were determined using a single XRD diffractometer.†

UV-vis and fluorescence titration

Stock solution of 30a (5 mM) and several other metal ions (1 × 10⁻³ M) were prepared in DMSO and Milli-Q water, respectively. The absorption or fluorescence spectra were recorded by adding small fractions of different metal ions to 3 mL of 9 : 1 DMSO/HEPES buffer (pH = 7.4, 10 mM) solution containing 25 μM 30a in a quartz cuvette (1 cm × 1 cm) with time interval of 1 min at room temperature.

Determination of quenching constant

The quenching constant (K_sv) values for Co²⁺ and Ni²⁺ were obtained by plotting a Stern–Volmer plot (I₀/I vs. [Q], where I₀ represents the initial fluorescence intensity of ligand 30a, I denotes fluorescence intensity of 30a after adding given concentration of quencher [Q], and [Q] = [Co²⁺] or [Ni²⁺]).

Determination of detection limit

The limit of detection (LOD) was calculated using the following equation³¹

LOD = 3σ/K

where, ‘σ’ denotes the standard deviation for the intensity of ligand 30a solution in the absence of Co²⁺/Ni²⁺ and ‘K’ represents the slope of the curve.

Method of drawing Job plot using fluorescence

Job's plot analysis^16a was performed to determine the stoichiometry between ligand 30a and Co²⁺/Ni²⁺. The summation of the concentration of ligand 30a and Co²⁺ was kept as constant c. Assuming the complex as non-fluorescent, the fluorescence intensity of 30a (F) can be calculated from the equation below:
where [30a] and [Co²⁺] denotes the concentration of ligand and Co²⁺ respectively and ‘a’ represents the complex ratio of ligand 30a and Co²⁺. Since summation of the concentration of ligand and Co²⁺ was kept as constant ‘c’, the above equation above could be modified as:

When the fluorescence of ligand is almost quenched by Co²⁺, i.e. F = 0, the complex ratio ‘a’ could be evaluated from the concentration of Co²⁺. Similar method can be used to calculate the complex ratio ‘a’ for ligand 30a and Ni²⁺.

General procedure for the preparation 4-hydroxy-3-thiomethylcoumarins

In 10 mL round bottomed flask, a mixture of aldehyde (1 mmol) and L-proline (0.1 mmol) was dissolved in 3 mL of ethanol and stirred at room temperature. After 10 min of stirring, 4-hydroxycoumarin (1 mmol) and thiol (1.2 mmol) were added either directly if it is a solid or drop-wise through a syringe, in quick succession. The solid products were precipitated out during the reaction after appropriate reaction time. Finally, the solid products were filtered off through a Büchner funnel, thoroughly washed with the mixture of ethanol and hexane (2 : 8) to remove unreacted starting material and recrystallized in 9 : 1 mixture of ethanol and chloroform. The following work up procedure was followed for the products in case the solid precipitate did not come out during the reaction time. After completion of reaction as checked by TLC, ethanol was removed under reduced pressure via a rotary evaporator and the crude residue was extracted with dichloromethane (2 × 15 mL). The organic layer was washed with water, brine solution (2 × 5 mL) and dried over anhydrous Na₂SO₄. Then, it was concentrated under reduced pressure and the crude residue was passed through a silica gel (60–120 mesh) column with gradient eluents of petroleum ether and ethyl acetate to get the desired pure product.

Acknowledgements

AAD and SH are thankful to IIT Guwahati for providing senior research fellowship. ATK is grateful to Council of Scientific and Industrial Research (CSIR) 02(0181)/14/EMR-II for their financial support. Financial assistance from Department of Science and Technology 80 (DST), New Delhi, (no. SB/S1/PC-020/2014), (no. DST/TSG/PT/2009/23), DST–Max Planck Society, Germany (IGSTC/MPG/PG(PKI)/2011A/48) is gratefully acknowledged by PKI. The authors are also grateful to Director, IIT Guwahati for providing the general research facility to carry out this work. We are also thankful to CIF, IIT Guwahati for providing the instrument facilities.

Notes and references

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Footnote

† Electronic supplementary information (ESI) available: Spectroscopic data ¹H NMR, ¹³C NMR, HRMS spectra for all compounds and X-ray data of compounds viz. 28a, Co-complex and Ni-complex. CCDC 1038726, 1038805 and 1038804. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c5ra09152g

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