Synthesis, characterization and gelation studies of a novel class of rhodamine based N-glycosylamines

Abstract

Twelve different rhodamine based N-glycosylamines were synthesized from the corresponding rhodamine based amine derivatives and 4,6-O-protected-D-glucose. All these compounds were characterized by using different spectral techniques and by their physico-chemical properties.

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Introduction

Recently, molecular organogels of low-molecular-weight organogelators (LMOGs) have attracted substantial attention^1–5 in supramolecular chemistry and materials science due to their unique characteristics and wide range of potential applications. In an organogel the gelator molecules self-assemble into nanoscale superstructures, such as fibers, rods, and ribbons through weak noncovalent interactions (i.e., hydrogen bonding, π–π stacking, van der Waals, coordination, and charge-transfer interactions).^6,7 Of particular interest for organogel material science are “smart gels”, i.e. gels whose properties can be controlled reversibly or irreversibly in response to changes in external chemical,^8,9 photochemical,^10,11 thermal sound.¹²

Gelator molecules and their gels have a wide range of application in tissue engineering,¹³ cosmetics,¹⁴ drug delivery¹⁵ etc. Among the gelators, non-ionic amphiphilic gelators having carbohydrate head groups are reported to have growing applications in the areas of foods, pharmaceuticals, detergents¹⁶ etc., and this is due to their ready biodegradability, mildness to skin, non-toxicity and synergistic effects in combination with anionic amphiphiles.¹⁷ Several non-ionic carbohydrate modified products are based on sorbitan,¹⁸ glycosides,¹⁹ sugar-esters,²⁰ including mannitol monoesters,²¹ and amides.²²

The structural modification of carbohydrate molecules to obtain LMOGs has been an interesting field of research in recent years.^23–25 Since carbohydrate molecules are biocompatible, the gels derived from these molecules have wide application in biology and also as functional materials.²⁶ Moreover, the abundant availability of saccharides enhances research into the design of novel sugar based gelator molecules. In the present study, we have synthesized and characterization of a series of rhodamine based N-glycosylamines and these derivatives exhibited excellent candidates for forming gels.

Result and discussion

Synthesis of rhodamine based N-glycosylamines

Rhodamine based amine derivatives (1–4),^27,28 4,6-O-ethylidene-D-glucopyranose (EGP),²⁹ 4,6-O-butylidene-D-glucopyranose (BGP),³⁰ and 4,6-O-benzylidene-D-glucopyranose (BzGP)³¹ were synthesized by adopting literature procedures. EGP (5), BGP (6), and BzGP (7) were further reacted with the rhodamine based amine derivatives (1–4) to give the corresponding rhodamine based N-glycosylamines (8–19) in 57–71% of yield (Scheme 1).

Scheme 1 Synthesis of rhodamine based N-glycosylamines (8–19).

Rhodamine based N-glycosylamines (8–19) were identified through spectral techniques. The ¹H NMR spectra of N-glycosylated products (8–19) showed the glycosylic-NH resonance at 4.5–6.0 ppm and chemical shift position of the acetal protons change with respect to the protecting group (BGP, EGP, BzGP), and the existence of the β-anomeric proton at 5.5 ppm in both the rhodamine based N-glycosylamine derivatives were identified from the corresponding coupling constant values and are given in Table 1. However ¹³C NMR studies show peaks around 17–41 ppm, 72–106 ppm and 110–162 ppm corresponding to the alkyl carbons, saccharide carbons and aromatic carbons respectively (see ESI for details†).

Table 1 Synthesis of rhodamine based N-glycosylamines (8–19)

Compounds	R1	R2	R′	N	t (h)	δ (H-1) (^3JH1,H2/Hz)	CGC (%) g mL^−1	Yield (%)
8	H	C2H5	CH3	2	4	3.86, 9.9	1.5	71
9	H	C2H5	C3H7	2	5	4.53, 7.2	1.0	65
10	H	C2H5	C6H5	2	8	3.91, 9.3	1.0	69
11	CH3	H	CH3	2	4	4.72, 9.9	1.5	64
12	CH3	H	C3H7	2	7	5.09, 7.3	1.0	57
13	CH3	H	C6H5	2	6	3.87, 9.0	1.5	60
14	H	C2H5	CH3	3	4	4.60, 7.5	1.5	62
15	H	C2H5	C3H7	3	8	3.56, 8.1	1.0	62
16	H	C2H5	C6H5	3	5	5.49, 8.7	1.0	70
17	CH3	H	CH3	3	9	4.60, 7.8	1.5	74
18	CH3	H	C3H7	3	5	4.07, 7.5	1.0	64
19	CH3	H	C6H5	3	5	4.67, 7.8	1.0	61

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Gelation studies

Recently, gelation studies were carried out by an inversion tube method,^24,25,32 where the compound dissolved in a suitable solvent which forms a homogeneous solution was heated and then cooled immediately to form a gel in Fig. 1. Critical gelation concentration (CGC) refers to the concentration at which a minimum amount of compound forms a gel (Table 1). In general, compounds with low CGC act as good gelators.

Fig. 1 Demonstration of the thermoreversible organogel of N-glycosylamine 8.

Twelve different rhodamine based N-glycosylamines (8–19) in eight different polar and non-polar organic solvents and the results of the gelation tests are summarised in Table 2. In general, protecting groups, such as, ethylidene, butylidene and benzylidene present on the D-glucose moiety led to remarkable change in the gelation process. The gelation ability of the organogelators significantly depends on the presence of alkyl and the xanthene groups. Greater gelating ability of butylidene protected N-glycosylamines (9, 12, 15 and 18), is due to higher London dispersion forces³³ existing between the alkyl chain groups. Such interactions are expected to be less in ethylidene protected N-glycosylamines (8, 11, 14 and 17) and the corresponding gelation would be low. However, in benzylidene protected N-glycosylamines (10, 13, 16 and 19) the π–π stacking interactions seem to be largely responsible for their gelation properties. These results support that partially protected rhodamine based N-glycosylamines with butylidene and benzylidene moieties have greater ability to undergo gelation compared to the ethylidene derivatives. Presence of the significant involvement of London dispersion forces and π–π interactions. These chemical factors are responsible for greater gelation ability of N-glycosylamines.

Table 2 Gelation studies of rhodamine based N-glycosylamines (8–19)^a

Solvents/compounds	C6H6	NO2C6H5	CH3C6H5	p-Xylene	CHCl3	DCM	Hexane	MeOH
a G = good gelators; PG = partial gelators; S = solution; P = precipitation; I = insoluble.
8	G	G	G	PG	PG	PG	I	S
9	PG	PG	G	G	S	P	P	S
10	S	PG	G	PG	PG	PG	I	S
11	PG	S	S	P	S	PG	S	S
12	G	G	G	G	G	G	S	S
13	PG	PG	G	G	S	G	P	S
14	S	PG	G	PG	PG	PG	P	S
15	PG	S	S	P	S	PG	S	S
16	G	G	PG	G	PG	PG	P	S
17	PG	PG	G	G	S	P	I	S
18	G	PG	G	PG	PG	PG	P	S
19	PG	G	G	G	S	PG	S	S

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Among the various polar and nonpolar solvents used for gelation of rhodamine based N-glycosylamines (8–19), the aliphatic solvents viz., chloroform, and dichloromethane were found to form gelation, which is due to the presence of alkyl chains. However, among the different aromatic solvents studied benzene, toluene, nitrobenzene and p-xylene were found to be the best solvents for the gelation process which may be attributed to a strong solute–solvent interaction. Partially protected N-glycosylamines viz., 8, 12, 16 and 19 were found to be good organogelators in nitrobenzene, whereas compounds, 9, 13 and 17 performed well in toluene and p-xylene. However, N-glycosylamine, 12 acts as an efficient organogelator in both solvents.

Photophysical studies

The absorption and emission spectra of the rhodamine based N-glycosylamines (8–19) were recorded at the concentration of 5 × 10⁻⁵ M in methanol. N-Glycosylamines (8–19) shows characteristic absorption bands in the range of 300–360 nm (Fig. 2). In addition, the number of methylene unit in alkyl chain and 4,6-O-protecting group in D-glucose unit does not influences the absorption maxima. On exciting the N-glycosylamines (8–19) at their absorption maxima of 300–315 nm they show corresponding emission band in the range of 345–380 nm (Fig. 3). Adsorption and emission spectra for xerogel and potential gelator are given in ESI.† From the comparative result, it could be observed that the potential gelator shows better than xerogel.

Fig. 2 Absorption spectra of rhodamine based N-glycosylamines (8–19).

Fig. 3 Emission spectra of rhodamine based N-glycosylamines (8–19).

Morphological studies

In order to obtain visual insight into the aggregation modes, SEM images were obtained, showing the presence of elongated nanofibers (Fig. 4). SEM images of rhodamine based N-glycosylamines (8–19) show well-defined 3D fibrous networks. SEM images of compound 8 formed intertwined thin sheets in nitrobenzene (Fig. 4a) with a width of 10–30 nm, and in toluene it formed quite a different microstructure as sponge-like structure (Fig. 4b) with a thickness about 7–10 nm. The surfaces of both the sponge-like structure and intertwined thin sheets were very smooth without any flaw. Compound 12 formed elongated nano fibers in benzene (Fig. 4c), around 10–50 nm and 13 formed ribbon-like architecture in toluene (Fig. 4d), with many interlinks between the fibrils. However, the organogelator 16 formed cross-linked nanofibrous structure with a large number of small bores in benzene (Fig. 4d) and 19 formed strips in p-xylene (Fig. 4e). Compound 12 acts as a good gelator, compared to the others. Three dimensional fibrous networks hold the solvent molecules together, which is due to the existence of surface tension in the gels. In addition, the presence of a channel-like architecture with different pore size is responsible for the gelation capacities.

Fig. 4 SEM images of organogel formed from (a) 8 in nitrobenzene; (b) 8 in toluene; (c) 12 in benzene; (d) 13 in toluene; (e) 16 in benzene; and (f) 19 in p-xylene.

Thermal analysis

DSC data obtained for 8 and 13 are shown in Fig. 5. The melting point and enthalpy of organogelator 8 in the solid phase are 172.4 °C and ΔH = 88.20 J g⁻¹ and in gel phase the values are 140.3 °C and 71.20 J g⁻¹. The organogelator, 13 shows melting point and enthalpy in solid phase at 148.9 °C (ΔH = 18.8 J g⁻¹) and gel phase 128.8 °C (ΔH = 67.01 J g⁻¹), respectively. These results indicate that organogel 13 is more stable in the solid phase.^34,35

Fig. 5 DSC spectra of (a) 8 (nitrobenzene), (b) 13 (toluene): () gel phase, () solid phase.

In the case of compound 8 in nitrobenzene T_gs of gel phase was found to lower than the solid phase while for compound 13 the T_gs of gel phase was found to be greater than that of solid phase. These results indicate that the gel phase of N-glycosylamine 8 has greater thermal stability than its corresponding solid phase, whereas for N-glycosylamine 13, the solid phase has greater thermal stability than its corresponding gel phase (Table 3).

Table 3 Thermodynamic parameters for sol–gel transition of N-glycosylamines (8 and 13)

Compounds	Tgs (°C)	ΔH (J g^−1)
8	140.3	71.20
13	128.8	67.01

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Rheological studies

The rheological properties of the gels of 8 (nitrobenzene) and 13 (toluene) were examined. The storage modulus, G′, was measured as a function of shear stress at room temperature. The results are shown in Fig. 6.

Fig. 6 Evolution of G′ as a function of the applied shear stress. Samples used are the gels of 8 and 13.

Comparison of the G′ values of the gels indicates that generally speaking the storage modulus of a gel increases along with increasing the alkyl chain of the gelator. From the figure it could be observed that gel is obeying to liner line up to a certain point after that its start to deform. The linear line is directly proportional to viscosity; therefore the linear line is associated with high viscosity, which in turn increases the viscoelastic properties of gel. The non linear line indicates the decreasing of the viscosity, while increasing the shear stress, which may be associated with structural breakage of component. From the rheology result (ESI†) the behaviour of the storage modulus (G′) and loss modulus (G′′) was observed. There is no significant change in the both modulus. Among them, it is apparent that the value of 13 is apparently larger than that of 8. Furthermore, the yield stresses of the gels are also dependent upon linker lengths of gelators. These results demonstrate clearly that the alkyl chain length of the gelators has a significant effect upon the mechanical properties of the resulting gels.

Powder XRD analysis

To reveal the detailed molecular packing modes of the gelators in the gels as prepared, XRD analyses of the powder sample of 13 and its xerogel from toluene were conducted. The results are depicted in Fig. 7. As shown in the figure, the XRD trace of powder 13 is characterized by nine sharp reflection peaks, and the corresponding spacings (d) are 0.96, 0.73, 0.64, 0.53, 0.44, 0.40, 0.37, 0.36 and 0.32 nm, respectively, indicating that the powder 13 possesses a layer structure. The xerogel of 13 from toluene, also shows four reflection peaks but in the larger angle region compared with the powder, and the obtained spacings (d) are 0.416, 0.320, 0.194, and 0.165 nm, respectively, which may be evidence of spherulite structure.^36–40

Fig. 7 Powder XRD profile of 13, (a) powder state; (b) xerogel state (from its toluene gel).

Conclusion

In summary, a novel class of rhodamine based N-glycosylamines were synthesized and characterized using by different spectral techniques. These compounds acts as good organogelators and are able to gelate even at CGC of 1 w/v%. Morphological, thermal and powder XRD studies show the various modes of aggregation and stability of gels, respectively, which depend on the protecting groups and also on the substituents in the rhodamine moiety.

Experimental section

D-Glucose, rhodamine-B and rhodamine-6G were purchased from Sd-fine, India. 1,2-Diaminoethane and 1,3-diaminopropane were purchased from Sigma Aldrich chemicals Pvt. Ltd, USA and were of high purity. Paraldehyde, butyraldehyde, and benzaldehyde dimethyl acetal were purchased from SRL, India. Chloroform and methanol were used after distillation. Column chromatography was performed on silica gel (100–200 mesh).

NMR spectra were recorded on a Bruker DRX 300 MHz, spectrometer. Elemental analysis was performed by using Perkin-Elmer 2400 series CHN analyser. The gels were imaged with a HITACHI-S-3400W Scanning Electron Microscope and optical rotation was performed using a Rudolph-Autopol II digital polarimeter. All absorption spectra were obtained with a UV-1600 UV/vis spectrometer (Shimadzu). All fluorescence spectra were obtained with an F4500 fluorescence spectrometer (Hitachi). Thermal transitions for gelators and gels were determined on a NETZSCH DSC 204 instrument. Rheological studies were recorded in Gemini 2000 using pp40. X-ray diffractograms of the dried films were recorded on XRD RINT 2500 diffractometer using Ni filtered Cu Kα radiation.

Preparation of gels

Rhodamine based N-glycosylamines 8–19 (1 mg) was placed in a glass vial and 1 mL of organic solvent was added. The gelator in the organic solvent was heated. The solution was then allowed to cool to room temperature whereby the gel formed.

General procedure for the synthesis of rhodamine based N-glycosylamines (8–19)

To a solution of rhodamine based amine derivatives (1–4) (1 mmol) in dry MeOH and 4,6-O-protected-D-glucopyranose (5–7) (1 mmol) were added. After stirring at reflux temperature for given period of time, the reaction mixture was evaporated under reduced pressure. The crude product was slurried with silica gel and purified by column chromatography. For details (reaction time and yields of products) see Table 1.

Physicochemical and spectral data for 4,6-O-ethylidine-N-(((rhodamine-B)-lactam)-ethyl)-β-D-glucopyranosylamine (8)

Compound 8 was obtained by the reaction of rhodamine B based ethylenediamine (1, 1 mmol, 0.48 g), and 4,6-O-ethylidine-β-D-glucopyranose (5, 1 mmol, 0.20 g) as a pale pink solid. Yield: 0.48 g (71%); mp 172–174 °C; [α]²³_D −31.4 (c 1.0 in CHCl₃); ¹H NMR (300 MHz, CDCl₃ + DMSO-d₆): δ 1.67 (t, 12H, J = 6.9 Hz, –CH₃), 1.35 (t, 3H, J = 4.8 Hz, –CH₃), 3.25–3.34 (m, 10H, –CH₂), 3.44–3.61 (m, 3H, Sac-H), 3.86 (d, 1H, J = 9.9 Hz, Ano-H), 4.02–4.11 (m, 2H, Sac-H), 4.36 (t, 2H, J = 3.3 Hz, Sac-H), 4.51–4.75 (m, 2H, –CH₂), 4.76 (s, 2H, Sac-OH), 5.16 (s, 1H, –NH), 6.27 (d, 1H, J = 7.2 Hz, Ar-H), 6.30 (d, 1H, J = 7.2 Hz, Ar-H), 6.37 (d, 2H, J = 7.2 Hz, Ar-H), 6.44 (d, 2H, J = 8.7 Hz, Ar-H), 7.05 (q, 1H, J = 7.2 Hz, Ar-H), 7.43–7.46 (m, 2H, Ar-H), 7.86 (q, 1H, J = 5.7 Hz, Ar-H). ¹³C NMR (75 MHz, CDCl₃ + DMSO-d₆): δ 17.3, 25.1, 48.3, 49.0, 65.6, 66.8, 70.1, 71.1, 73.0, 73.3, 75.4, 78.1, 80.8, 85.1, 85.7, 97.8, 102.3, 102.5, 104.1, 109.6, 112.8, 127.3, 128.5, 132.8, 133.1, 135.2, 137.3, 153.5, 157.9, 158.5, 173.9. Anal. calcd for C₃₈H₄₈N₄O₇: C, 67.84; H, 7.19; N, 8.33. Found: C, 67.87; H, 7.16; N, 8.37%.

Physicochemical and spectral data for 4,6-O-butylidine-N-(((rhodamine-B)-lactam)-ethyl)-β-D-glucopyranosylamine (9)

Compound 9 was obtained by the reaction of rhodamine B based ethylenediamine (1, 1 mmol, 0.48 g), and 4,6-O-butylidine-β-D-glucopyranose (6, 1 mmol, 0.23 g) as a pale pink solid. Yield: 0.46 g (65%); mp 166–168 °C; [α]²³_D −48.2 (c 1.0 in CHCl₃); ¹H NMR (300 MHz, CDCl₃ + DMSO-d₆): δ 0.89 (t, 3H, J = 7.2 Hz, –CH₃), 1.15 (t, 12H, J = 6.9 Hz, –CH₃), 1.37–1.45 (m, 2H, –CH₂), 1.58–1.61 (m, 2H, –CH₂), 3.22 (q, 5H, J = 5.2 Hz, Sac-H), 3.30–3.37 (m, 8H, –CH₂), 3.41–3.81 (m, 2H, Sac-H), 4.00–4.05 (m, 4H, –CH₂), 4.38 (s, 2H, Sac-OH), 4.53 (d, 1H, J = 7.2 Hz, Ano-H), 5.11 (s, 1H, –NH), 6.27 (dd, 2H, J = 8.7 Hz, Ar-H), 6.35 (d, 2H, J = 7.1 Hz, Ar-H), 6.41 (d, 2H, J = 9.0 Hz, Ar-H), 7.03 (q, 1H, J = 6.9 Hz, Ar-H), 7.44 (q, 2H, J = 7.2 Hz, Ar-H), 7.83 (q, 1H, J = 7.2 Hz, Ar-H). ¹³C NMR (75 MHz, CDCl₃ + DMSO-d₆): δ 17.2, 22.1, 25.2, 41.0, 48.0, 49.0, 65.2, 67.0, 69.9, 71.3, 73.4, 75.4, 78.2, 85.9, 97.9, 102.5, 106.9, 109.7, 112.8, 127.3, 128.5, 132.8, 133.2, 135.3, 137.3, 153.5, 157.9, 158.5, 173.5. HRMS (ES+): m/z calcd for C₄₀H₅₂N₄O₇: 700.3858. Found: 700.3845 (M + H)⁺; elemental analysis: anal. calcd for C₄₀H₅₂N₄O₇: C, 68.55; H, 7.48; N, 7.99. Found: C, 68.57; H, 7.45; N, 7.96%.

Physicochemical and spectral data for 4,6-O-benzylidine-N-(((rhodamine-B)-lactam)-ethyl)-β-D-glucopyranosylamine (10)

Compound 10 was obtained by the reaction of rhodamine B based ethylenediamine (1, 1 mmol, 0.48 g), and 4,6-O-benzylidine-β-D-glucopyranose (7, 1 mmol, 0.26 g) as a pale pink solid. Yield: 0.51 g (69%); mp 179–181 °C; [α]²³_D −76.8 (c 1.0 in CHCl₃); ¹H NMR (300 MHz, CDCl₃ + DMSO-d₆): δ 1.15 (t, 12H, J = 6.9 Hz, –CH₃), 3.09 (d, 2H, J = 4.2 Hz, Sac-H), 3.25–3.41 (m, 8H, –CH₂), 3.44–3.78 (m, 5H, Sac-H), 3.91 (d, 1H, J = 9.3 Hz, Ano-H), 3.98–4.07 (m, 1H, Sac-H), 4.18–4.36 (m, 3H, Sac-H), 4.85 (s, 1H, Sac-OH), 5.19 (s, 1H, Sac-OH), 5.51 (s, 1H, –NH), 6.27 (dd, 2H, J = 9.0 Hz, Ar-H), 6.36 (d, 2H, J = 7.2 Hz, Ar-H), 6.43 (d, 2H, J = 8.7 Hz, Ar-H), 7.04 (q, 2H, J = 7.2 Hz, Ar-H), 7.32 (t, 3H, J = 7.8 Hz, Ar-H), 7.43–7.49 (m, 3H, Ar-H), 7.84 (q, 1H, J = 6.9 Hz, Ar-H). ¹³C NMR (75 MHz, CDCl₃ + DMSO-d₆): δ 17.3, 48.3, 49.0, 65.6, 66.9, 70.1, 71.1, 73.5, 73.9, 75.3, 78.1, 80.8, 85.8, 86.4, 97.9, 102.4, 102.5, 106.4, 109.6, 112.8, 127.3, 128.5, 131.2, 132.8, 133.1, 133.7, 135.2, 137.3, 153.5, 157.9, 158.5, 173.8. HRMS (ES+): m/z calcd for C₄₃H₅₀N₄O₇: 734.3767. Found: 734.3754 (M + H)⁺; elemental analysis: anal. calcd for C₄₃H₅₀N₄O₇: C, 70.28; H, 6.86; N, 7.62. Found: C, 70.25; H, 6.84; N, 7.64%.

Physicochemical and spectral data for 4,6-O-ethylidine-N-(((rhodamine-6G)-lactam)-ethyl)-β-D-glucopyranosylamine (11)

Compound 11 was obtained by the reaction of rhodamine 6G based ethylenediamine (2, 1 mmol, 0.45 g), and 4,6-O-ethylidine-β-D-glucopyranose (5, 1 mmol, 0.20 g) as a pale pink solid. Yield: 0.41 g (64%); mp 168–170 °C; [α]²³_D −87.5 (c 1.0 in CHCl₃); ¹H NMR (300 MHz, CDCl₃ + DMSO-d₆): δ 1.35 (t, 9H, J = 5.4 Hz, –CH₃), 1.92 (s, 6H, –CH₃), 3.23 (m, 4H, –CH₂), 3.48 (t, 3H, J = 10.2 Hz, Sac-H), 3.62 (s, 2H, Sac-OH), 3.79–3.88 (m, 4H, –CH₂), 3.98–4.06 (m, 3H, Sac-H), 4.43 (s, 2H, –NH), 4.60 (q, 1H, J = 6.2 Hz, Sac-H), 4.72 (d, 1H, J = 9.9 Hz, Ano-H), 5.16 (t, 1H, J = 3.6 Hz, Sac-H), 6.18 (d, 2H, J = 7.8 Hz, Ar-H), 6.36 (s, 2H, Ar-H), 7.03 (q, 1H, J = 7.4 Hz, Ar-H), 7.46 (q, 2H, J = 8.0 Hz, Ar-H), 7.91 (q, 1H, J = 6.9 Hz, Ar-H). ¹³C NMR (75 MHz, CDCl₃ + DMSO-d₆): δ 17.9, 22.6, 25.2, 42.9, 66.8, 70.7, 71.1, 72.9, 73.3, 75.3, 78.1, 80.8, 85.1, 85.8, 97.9, 101.4, 102.3, 104.0, 109.4, 122.8, 127.5, 128.4, 132.1, 132.9, 134.4, 137.3, 152.3, 156.5, 156.8, 170.7. HRMS (ES+): m/z calcd for C₃₆H₄₄N₄O₇ + H: 644.3263. Found: 644.3254 (M + H)⁺; elemental analysis: anal. calcd for C₃₆H₄₄N₄O₇: C, 67.06; H, 6.88; N, 8.69. Found: C, 67.08; H, 6.86; N, 8.66%.

Physicochemical and spectral data for 4,6-O-butylidine-N-(((rhodamine-6G)-lactam)-ethyl)-β-D-glucopyranosylamine (12)

Compound 12 was obtained by the reaction of rhodamine 6G based ethylenediamine (2, 1 mmol, 0.45 g), and 4,6-O-butylidine-β-D-glucopyranose (6, 1 mmol, 0.23 g) as a pale pink solid. Yield: 0.38 g (57%); mp 161–163 °C; [α]²³_D −60.4 (c 1.0 in CHCl₃); ¹H NMR (300 MHz, CDCl₃ + DMSO-d₆): δ 0.85 (t, 3H, J = 7.2 Hz, –CH₃), 1.27 (t, 6H, J = 6.9 Hz, –CH₃), 1.34–1.41 (m, 2H, –CH₂), 1.55–1.58 (m, 2H, –CH₂), 1.87 (s, 6H, –CH₃), 3.13–3.17 (m, 4H, –CH₂), 3.41 (t, 2H, J = 6.2 Hz, Sac-H), 3.58 (s, 2H, Sac-OH), 3.78 (s, 4H, –CH₂), 3.93–4.02 (m, 3H, Sac-H), 4.35 (s, 2H, –NH), 4.49 (t, 3H, J = 4.8 Hz, Sac-H), 5.09 (d, 1H, J = 7.3 Hz, Ano-H), 6.15 (d, 2H, J = 7.2 Hz, Ar-H), 6.31 (s, 2H, Ar-H), 6.98 (q, 1H, J = 6.9 Hz, Ar-H), 7.41 (q, 2H, J = 7.8 Hz, Ar-H), 7.85 (q, 1H, J = 7.8 Hz, Ar-H). ¹³C NMR (75 MHz, CDCl₃ + DMSO-d₆): δ 18.7, 19.4, 21.6, 22.1, 41.0, 42.9, 67.0, 70.7, 73.4, 75.5, 78.2, 85.8, 97.8, 101.4, 106.9, 122.7, 128.4, 132.1, 132.8, 134.4, 137.3, 152.3, 156.5, 156.8, 170.7. HRMS (ES+): m/z calcd for C₃₈H₄₈N₄O₇ + H: 672.3553. Found: 672.3542 (M + H)⁺; elemental analysis: anal. calcd for C₃₈H₄₈N₄O₇: C, 67.84; H, 7.19; N, 8.33. Found: C, 67.87; H, 7.16; N, 8.36%.

Physicochemical and spectral data for 4,6-O-benzylidine-N-(((rhodamine-6G)-lactam)-ethyl)-β-D-glucopyranosylamine (13)

Compound 13 was obtained by the reaction of rhodamine 6G based ethylenediamine (2, 1 mmol, 0.45 g), and 4,6-O-benzylidine-β-D-glucopyranose (7, 1 mmol, 0.26 g) as a pale pink solid. Yield: 0.42 g (60%); mp 146–148 °C; [α]²³_D −75.2 (c 1.0 in CHCl₃); ¹H NMR (300 MHz, CDCl₃ + DMSO-d₆): δ 1.29 (t, 6H, J = 6.9 Hz, –CH₃), 1.89 (s, 6H, –CH₃), 3.15–3.29 (m, 4H, –CH₂), 3.38–3.50 (m, 3H, Sac-H), 3.61–3.75 (m, 3H, Sac-H), 3.87 (d, 1H, J = 9.0 Hz, Ano-H), 3.95–4.03 (m, 1H, Sac-H), 4.15–4.26 (m, 1H, Sac-H), 4.58–4.68 (m, 4H, –CH₂), 4.82 (s, 1H, Sac-OH), 5.15 (s, 1H, Sac-OH), 5.49 (s, 2H, –NH), 6.18 (s, 2H, Ar-H), 6.33 (s, 2H, Ar-H), 6.99 (q, 1H, J = 6.7 Hz, Ar-H), 7.30 (t, 3H, J = 8.2 Hz, Ar-H), 7.42–7.48 (m, 4H, Ar-H), 7.86 (q, 1H, J = 7.2 Hz, Ar-H). ¹³C NMR (75 MHz, CDCl₃ + DMSO-d₆): δ 19.4, 21.6, 42.9, 66.9, 70.7, 71.8, 75.3, 78.1, 80.8, 85.8, 86.5, 98.0, 101.4, 102.5, 106.3, 106.4, 109.5, 122.7, 128.4, 131.2, 131.3, 132.1, 132.8, 133.7, 134.5, 137.2, 152.3, 156.5, 156.8, 170.7. Anal. calcd for C₄₁H₄₆N₄O₇: C, 69.67; H, 6.56; N, 7.93. Found: C, 69.65; H, 6.58; N, 7.95%.

Physicochemical and spectral data for 4,6-O-ethylidine-N-(((rhodamine-B)-lactam)-propyl)-β-D-glucopyranosylamine (14)

Compound 14 was obtained by the reaction of rhodamine B based 1,3-propylenediamine (3, 1 mmol, 0.49 g), and 4,6-O-ethylidine-β-D-glucopyranose (5, 1 mmol, 0.20 g) as a pale pink solid. Yield: 0.42 g (62%); mp 150–152 °C; [α]²³_D −72.6 (c 1.0 in CHCl₃); ¹H NMR (300 MHz, CDCl₃ + DMSO-d₆): δ 1.16 (t, 12H, J = 6.9 Hz, –CH₃), 1.34 (t, 3H, J = 4.2 Hz, –CH₃), 3.31–3.37 (m, 8H, –CH₂), 3.49 (d, 2H, J = 9.9 Hz, Sac-H), 3.62 (d, 1H, J = 6.6 Hz, Sac-H), 3.78–3.88 (m, 2H, Sac-H), 4.02–4.09 (m, 2H, Sac-H), 4.52 (s, 2H, Sac-OH), 4.60 (d, 1H, J = 7.5 Hz, Ano-H), 4.70–4.73 (m, 6H, –CH₂), 5.17 (s, 1H, –NH), 6.26 (q, 2H, J = 6.9 Hz, Ar-H), 6.37 (q, 4H, J = 7.2 Hz, Ar-H), 7.05–7.10 (m, 1H, Ar-H), 7.45 (q, 2H, J = 9.6 Hz, Ar-H), 7.86 (q, 1H, J = 7.2 Hz, Ar-H). ¹³C NMR (75 MHz, CDCl₃ + DMSO-d₆): δ 12.4, 20.2, 28.5, 37.3, 44.1, 62.0, 66.2, 67.2, 68.1, 68.5, 70.5, 73.1, 74.6, 75.9, 80.1, 80.3, 80.7, 91.1, 92.9, 97.3, 97.5, 99.2, 107.9, 122.4, 123.6, 127.9, 128.5, 132.2, 148.6, 153.1, 168.1. Anal. calcd for C₃₉H₅₀N₄O₇: C, 68.20; H, 7.34; N, 8.16. Found: C, 68.23; H, 7.37; N, 8.13%.

Physicochemical and spectral data for 4,6-O-butylidine-N-(((rhodamine-B)-lactam)-propyl)-β-D-glucopyranosylamine (15)

Compound 15 was obtained by the reaction of rhodamine B based 1,3-propylenediamine (3, 1 mmol, 0.49 g), and 4,6-O-butylidine-β-D-glucopyranose (6, 1 mmol, 0.23 g) as a pale pink solid. Yield: 0.44 g (62%); mp 144–147 °C; [α]²³_D −77.5 (c 1.0 in CHCl₃); ¹H NMR (300 MHz, CDCl₃ + DMSO-d₆): δ 0.87 (t, 3H, J = 7.5 Hz, –CH₃), 1.13 (t, 12H, J = 6.9 Hz, –CH₃), 1.34–1.42 (m, 2H, –CH₂), 1.54–1.60 (m, 2H, –CH₂), 3.11–3.13 (m, 4H, Sac-H), 3.14 (s, 2H, Sac-OH), 3.16–3.18 (m, 2H, Sac-H), 3.56 (d, 1H, J = 8.1 Hz, Ano-H), 3.73–4.10 (m, 8H, –CH₂), 4.49–4.56 (m, 6H, –CH₂), 5.05 (s, 1H, –NH), 5.12 (d, 1H, J = 3.6 Hz, Sac-H), 6.23 (q, 2H, J = 9.0 Hz, Ar-H), 6.34 (q, 4H, J = 7.2 Hz, Ar-H), 7.02 (q, 1H, J = 6.9 Hz, Ar-H), 7.42 (t, 2H, J = 7.2 Hz, Ar-H), 7.82 (q, 1H, J = 7.5 Hz, Ar-H). ¹³C NMR (75 MHz, CDCl₃ + DMSO-d₆): δ 17.3, 18.7, 22.1, 40.9, 41.0, 49.0, 67.0, 71.2, 73.0, 73.4, 75.3, 78.0, 80.7, 85.1, 85.7, 96.0, 97.8, 102.2, 102.4, 106.9, 110.1, 112.7, 127.3, 128.4, 132.8, 133.4, 153.5, 158.0, 172.8. Anal. calcd for C₄₁H₅₄N₄O₇: C, 68.88; H, 7.61; N, 7.84. Found: C, 68.85; H, 7.63; N, 7.86%.

Physicochemical and spectral data for 4,6-O-benzylidine-N-(((rhodamine-B)-lactam)-propyl)-β-D-glucopyranosylamine (16)

Compound 16 was obtained by the reaction of rhodamine B based 1,3-propylenediamine (3, 1 mmol, 0.49 g), and 4,6-O-benzylidine-β-D-glucopyranose (7, 1 mmol, 0.26 g) as a pale pink solid. Yield: 0.52 g (70%); mp 162–164 °C; [α]²³_D −97.4 (c 1.0 in CHCl₃); ¹H NMR (300 MHz, CDCl₃ + DMSO-d₆): δ 1.15 (t, 12H, J = 6.9 Hz, –CH₃), 3.11–3.18 (m, 4H, Sac-H), 3.29–3.34 (m, 8H, –CH₂), 3.43 (t, 1H, J = 9.3 Hz, Sac-H), 3.59–3.71 (m, 6H, –CH₂), 3.84 (d, 1H, J = 8.4 Hz, Sac-H), 4.19 (q, 1H, J = 7.2 Hz, Sac-H), 4.68 (s, 2H, Sac-OH), 5.26 (s, 1H, –NH), 5.49 (d, 1H, J = 8.7 Hz, Ano-H), 6.25 (q, 2H, J = 8.7 Hz, Ar-H), 6.33–6.39 (m, 4H, Ar-H), 7.05 (q, 1H, J = 7.8 Hz, Ar-H), 7.31 (t, 3H, J = 8.8 Hz, Ar-H), 7.41–7.48 (m, 4H, Ar-H), 7.85 (q, 1H, J = 8.2 Hz, Ar-H). ¹³C NMR (75 MHz, CDCl₃ + DMSO-d₆): δ 17.3, 33.5, 42.2, 49.0, 69.8, 72.1, 73.6, 78.6, 79.4, 85.9, 96.1, 102.4, 106.3, 110.3, 112.7, 127.3, 128.4, 131.1, 132.8, 133.4, 133.6, 135.9, 137.1, 142.2, 153.5, 158.0, 158.2, 172.8. Anal. calcd for C₄₄H₅₂N₄O₇: C, 70.57; H, 7.00; N, 7.48. Found: C, 70.59; H, 7.03; N, 7.45%.

Physicochemical and spectral data for 4,6-O-ethylidine-N-(((rhodamine-6G)-lactam)-propyl)-β-D-glucopyranosylamine (17)

Compound 17 was obtained by the reaction of rhodamine 6G based 1,3-propylenediamine (4, 1 mmol, 0.47 g), and 4,6-O-ethylidine-β-D-glucopyranose (5, 1 mmol, 0.20 g) as a pale pink solid. Yield: 0.48 g (74%); mp 142–144 °C; [α]²³_D −32.2 (c 1.0 in CHCl₃); ¹H NMR (300 MHz, CDCl₃ + DMSO-d₆): δ 1.13 (t, 9H, J = 6.9 Hz, –CH₃), 1.90 (s, 6H, –CH₃), 3.15–3.25 (m, 6H, –CH₂), 3.31 (d, 1H, J = 8.4 Hz, Sac-H), 3.42–3.54 (m, 2H, Sac-H), 3.65 (q, 3H, J = 6.7 Hz, Sac-H), 3.75 (d, 1H, J = 8.4 Hz, Sac-H), 3.84–3.90 (m, 2H, Sac-H), 4.02 (s, 2H, Sac-OH), 4.60 (d, 1H, J = 7.8 Hz, Ano-H), 4.69–4.75 (m, 4H, –CH₂), 5.17 (s, 1H, –NH), 6.16 (d, 2H, J = 7.2 Hz, Ar-H), 6.33 (s, 2H, Ar-H), 7.03 (t, 1H, J = 7.2 Hz, Ar-H), 7.46 (q, 2H, J = 7.8 Hz, Ar-H), 7.85 (q, 1H, J = 7.8 Hz, Ar-H).¹³C NMR (75 MHz, CDCl₃ + DMSO-d₆): δ 17.8, 19.8, 20.0, 23.5, 23.6, 23.8, 41.5, 65.4, 68.4, 69.6, 71.5, 71.7, 71.9, 73.9, 76.5, 76.6, 81.3, 83.5, 84.2, 96.3, 99.7, 100.7, 102.6, 104.5, 105.9, 108.9, 121.1, 125.8, 126.9, 131.4, 131.5, 135.6, 150.7, 154.9, 171.2. Anal. calcd for C₃₇H₄₆N₄O₇: C, 67.46; H, 7.04; N, 8.50. Found: C, 67.49; H, 7.07; N, 8.52%.

Physicochemical and spectral data for 4,6-O-butylidine-N-(((rhodamine-6G)-lactam)-propyl)-β-D-glucopyranosylamine (18)

Compound 18 was obtained by the reaction of rhodamine 6G based 1,3-propylenediamine (4, 1 mmol, 0.47 g), and 4,6-O-butylidine-β-D-glucopyranose (6, 1 mmol, 0.23 g) as a pale pink solid. Yield: 0.53 g (64%); mp 156–159 °C; [α]²³_D −67.6 (c 1.0 in CHCl₃); ¹H NMR (300 MHz, CDCl₃ + DMSO-d₆): δ 0.88 (t, 6H, J = 7.2 Hz, –CH₃), 1.29 (t, 3H, J = 6.6 Hz, –CH₃), 1.36–1.43 (m, 2H, –CH₂), 1.57–1.61 (m, 2H, –CH₂), 1.88 (s, 6H, –CH₃), 3.42–3.54 (m, 6H, –CH₂), 3.75–3.85 (m, 4H, Sac-H), 3.91 (s, 2H, Sac-OH), 3.98–4.05 (m, 5H, Sac-H), 4.07 (d, 1H, J = 7.5 Hz, Ano-H), 4.50–4.52 (m, 4H, –CH₂), 5.10 (s, 1H, –NH), 6.12 (s, 2H, Ar-H), 6.29 (s, 2H, Ar-H), 6.99 (s, 1H, Ar-H), 7.45 (s, 2H, Ar-H), 7.84 (s, 1H, Ar-H). ¹³C NMR (75 MHz, CDCl₃ + DMSO-d₆): δ 21.6, 25.2, 25.3, 42.9, 66.8, 71.1, 72.9, 73.3, 75.2, 78.1, 80.8, 85.2, 85.8, 97.9, 101.4, 102.4, 103.4, 104.0, 110.4, 122.9, 127.2, 128.5, 132.9, 137.2, 152.3, 156.4, 172.6. Anal. calcd for C₃₉H₅₀N₄O₇: C, 68.20; H, 7.34; N, 8.16. Found: C, 68.22; H, 7.37; N, 8.18%.

Physicochemical and spectral data for 4,6-O-benzylidine-N-(((rhodamine-6G)-lactam)-propyl)-β-D-glucopyranosylamine (19)

Compound 19 was obtained by the reaction of rhodamine 6G based 1,3-propylenediamine (4, 1 mmol, 0.47 g), and 4,6-O-benzylidine-β-D-glucopyranose (7, 1 mmol, 0.26 g) as a pale pink solid. Yield: 0.44 g (61%); mp 172–174 °C; [α]²³_D −87.4 (c 1.0 in CHCl₃); ¹H NMR (300 MHz, CDCl₃ + DMSO-d₆): δ 1.33 (t, 6H, J = 6.9 Hz, –CH₃), 1.92 (s, 6H, –CH₃), 3.20–3.48 (m, 6H, –CH₂), 3.50–3.58 (m, 4H, Sac-H), 3.66–3.78 (m, 4H, –CH₂), 3.81–4.33 (m, 3H, Sac-H), 4.67 (d, 1H, J = 7.8 Hz, Ano-H), 5.23 (d, 2H, J = 3.6 Hz, Sac-H), 5.51 (s, 2H, Sac-OH), 5.23 (s, 1H, –NH), 6.19 (d, 2H, J = 7.2 Hz, Ar-H), 6.36 (s, 2H, Ar-H), 7.05 (d, 1H, J = 7.4 Hz, Ar-H), 7.35 (t, 4H, J = 7.2 Hz, Ar-H), 7.48–7.51 (m, 3H, Ar-H), 7.91 (q, 1H, J = 7.0 Hz, Ar-H). ¹³C NMR (75 MHz, CDCl₃ + DMSO-d₆): δ 19.3, 21.2, 21.5, 43.0, 66.9, 71.1, 73.5, 73.9, 75.4, 78.0, 80.7, 81.9, 85.7, 86.3, 97.9, 101.2, 102.3, 106.4, 122.7, 128.4, 130.8, 130.9, 131.1, 131.2, 131.3, 132.8, 133.0, 133.7, 142.2, 142.3, 142.6, 152.3, 156.3, 172.8. Anal. calcd for C₄₂H₄₈N₄O₇: C, 69.98; H, 6.71; N, 7.77. Found: C, 69.95; H, 6.71; N, 7.75%.

Acknowledgements

Authors acknowledge SERC, New Delhi for the financial support. T. M. thanks Central University of Tamil Nadu (CUTN), Thiruvarur, Tamil Nadu for infrastructure facilities. T. M. thanks DST, New Delhi for 300 MHz NMR spectrometer under the FIST scheme to the Department of Organic Chemistry, University of Madras. T. M. thanks Dr S. Balakumar, Department of National Centre for Nanoscience and Nanotechnology, University of Madras, Chennai-600 025 for morphological studies. M. R. thanks UGC-SRF, New Delhi for a Research Fellowship.

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Footnote

† Electronic supplementary information (ESI) available: NMR spectrum. See DOI: 10.1039/c4ra03198a

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