Synthesis and Bactericidal Efficacy of Novel Dendrimers

Abstract

Synthesis of dendrimers with enones as the core unit and m-terphenyl as surface end group has been achieved. All the enones and the dendrimers were antibacterial against Salmonella typhi, ­Salmonella paratyphi and Staphylococcus aureus.

Key words

dendrimers - enone - m-terphenyl - antibacterial - salmonella typhi

References

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General Procedure for the Preparation of Dendrimer.
A mixture of dienone 6/diketone 7 (1 mmol) and dendritic bromide 4/9/12 (2.1 mmol) was stirred with K₂CO₃ (5 mmol) in DMF (20 mL) at 60 °C for 48 h. The reaction mixture was poured into H₂O and extracted with CH₂Cl₂ (3 × 150 mL). The combined organic extracts were washed with brine (80 mL), water (2 × 100 mL) and dried over MgSO₄. Evaporation of the organic layer gave a residue, which was purified by chromatography over SiO₂ gel using CHCl₃ as eluent to give the corresponding dendrimer.

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Dendrimer 1a: yield 44%; CHCl₃; mp 88-92 °C. ¹H NMR (500 MHz, CDCl₃): δ = 5.14 (s, 4 H), 6.86-6.98 (d, 4 H), 7.17-7.70 (m, 34 H). ¹³C NMR (125 MHz, CDCl₃): δ = 70.1, 115.3, 123.6, 125.2, 126.0, 127.7, 127.6, 128.0, 128.8, 130.1, 137.5, 140.7, 142.3, 142.6, 160.7, 188.8. MS (FAB, 70 eV): m/z = 750 [M⁺]. Anal. Calcd for C₅₅H₄₂O₃: C, 88.00; H, 5.60. Found: C, 87.98; H, 5.56.

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Dendrimer 2a: yield 45%; CHCl₃; mp 174-176 °C. ¹H NMR (500 MHz, CDCl₃): δ = 5.20 (s, 4 H), 7.04-7.05 (d, 4 H), 7.17-8.00 (m, 38 H). ¹³C NMR (125 MHz, CDCl₃): δ = 70.2, 76.7, 114.8, 122.7, 125.2, 126.1, 127.2, 127.6, 128.8, 129.2, 130.9, 131.2, 137.2, 140.7, 142.3, 142.8, 188.4. MS (FAB, 70 eV): m/z = 854 [M ⁺ ]. Anal. Calcd for C₆₂H₄₆O₄: C, 87.11; H, 5.38. Found: C, 87.05; H, 5.32.

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Dendrimer 1b: yield 51%; CHCl₃; mp 114-116 °C. ¹H NMR (500 MHz, CDCl₃): δ = 4.90 (s, 4 H), 5.00 (s, 8 H), 6.49 (d, 2 H), 6.57 (d, 2 H), 7.18-7.59 (m, 66 H). ¹³C NMR (125 MHz, CDCl₃): δ = 69.9, 70.2, 101.8, 106.4, 115.3, 125.3, 125.9, 127.3, 127.6, 127.9, 128.8, 130.0, 137.7, 139.1, 140.8, 142.2, 142.6, 143.6, 160.2, 160.5,188.8. MS (FAB, 70 eV): m/z = 1478 [M ⁺ ]. Anal. Calcd for C₁₀₇H₈₂O₇: C, 86.87; H, 5.54. Found: C, 88.76; H, 5.46.
Dendrimer 2b: yield 48%; CHCl₃; mp 106-108 °C. ¹H NMR (500 MHz, CDCl₃): δ = 5.19 (s, 4 H), 5.22 (s, 8 H), 6.73-6.77 (d, 4 H), 7.39-7.79 (m, 70 H). ¹³C NMR (125 MHz, CDCl₃): δ = 65.4, 70.1, 70.2, 70.3, 101.4, 101.9, 105.9, 106.5, 114.9, 125.4, 126.0, 127.4, 127.7, 128.9,130.9, 137.8, 140.9, 142.3, 160.3, 160.4, 162.6, 188.4. MS (FAB, 70 eV): m/z = 1582 [M ⁺ ]. Anal. Calcd for C₁₁₄H₈₆O₈: C, 86.47; H, 5.43. Found: C, 86.40; H, 5.36.

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Dendrimer 1c: yield 58%; CHCl₃; yellow colored liquid. ¹H NMR (500 MHz, CDCl₃): δ = 4.98 (s, 4 H), 5.01 (s, 8 H), 5.13 (s, 16 H), 6.70 (d, 2 H), 6.78 (d, 2 H), 7.18-7.81 (m, 130 H). ¹³C NMR (125 MHz, CDCl₃): δ = 68.1, 70.1, 101.2, 101.8, 106.6, 115.3, 125.4, 127.4, 127.7, 128.9, 137.9, 139.4, 140.9, 142.3, 160.2, 160.3, 160.6, 188.6. MS (MALDI-TOF): m/z = 2934 [M ⁺ ]. Anal. Calcd for C₂₁₁H₁₆₂O₁₅: C, 86.29; H, 5.52. Found: C, 86.20; H, 5.42.
Dendrimer 2c: yield 51%; CHCl₃; yellow colored liquid. ¹H NMR (500 MHz, CDCl₃): δ = 5.00 (s, 4 H), 5.02 (s, 8 H), 5.14 (s, 16 H), 6.67-6.70 (dd, 2 H), 6.75 (d, 2 H), 7.34-7.64 (m, 134 H). ¹³C NMR (125 MHz, CDCl₃): δ = 70.1, 70.2, 101.7, 106.5, 114.8, 125.4, 126.0, 127.4, 127.6, 128.9, 137.8, 139.4, 140.9, 142.2, 160.2, 160.3, 188.4. MS (MALDI-TOF): m/z = 3038 [M⁺]. Anal. Calcd for C₂₁₈H₁₆₆O₁₆: C, 86.10; H, 5.46. Found: C, 86.06; H, 5.40.

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Antibacterial activity: All the test bacteria were subcultured in nutrient broth from which 1 mL of cell suspension was taken and was adjusted to 0.5 OD. This was spread as a thin film over the nutrient agar plates. Concentrations of 60, 40 and 20 µg/mL of the compound were loaded into a disc, which was placed over the inoculated plates. All the plates were incubated for 48 h at 37 °C and growth was measured. A streptomycin disc from Hi-media (10 µg/disc) was used as the standard.