Supporting Information

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Supporting Information

Gold Nanoparticles Functionalized With Deep-cavity Cavitands: Synthesis, Characterization and Photophysical Studies

Shampa R.Samanta, Revathy Kulasekharan, Rajib Choudhury, Pradeepkumar Jagadesan, Nithyanandhan Jayaraj and V. Ramamurthy*

Department of Chemistry, University of Miami, Coral Gables, FL, 33124, United States

Contents Page

Structures of hosts and guests used in this study (Scheme S1) S2

Overall synthetic scheme to prepare four new cavitands (Scheme S2) S3

Synthesis and characterization of cavitands TT, TAm, TATP and TTTA S4-S12

Synthesis and characterization of cavitand functionalized AuNP S13-S17

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H NMR spectra of inclusion of guests within cavitand TT in DMSO S18-S21

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H NMR spectra of guests included within TT∩AuNP in DMSO S22-S25

Isothermal titration calorimetric studies on guest inclusion within TT and TT∩AuNP S26-S29

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H NMR spectra of inclusion of guests within cavitand TTTA in water S30-S33

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H NMR spectra of inclusion of guests within cavitand TTTA∩AuNP in water S34-S35

1

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S2 R₂ O O O _O _O _O O _O O O O O O O _O O R₁ R1 R1 R1 R₂ R2 R₂ e c d f g h i j k b R₁ CH2SH CH2SH CH₂OH TATP O O O O CH₃ CH₃ e 1 2 3 4 5 6 S S R₃ Br CH2COOH 7 8 9 Cl 10 11 12 13 ~ 9.3 Å ~ 11.7 Å R₁ TAm OAm TT TTTA a

Hosts

COOH OA CH₂N(CH₂CH₃)₂ CH₂N(CH₂CH₃)₂

Guests

3 2 1 6 4 5 R₂ H CH₂N(CH₂CH₃)₂ COOH H COOH OH R₂ R₃ a

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S3 Compound 1, A and D were

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Synthetic Procedure:

Compound 1, A and D were synthesized by following reported procedure in reference 1. Based on synthetic procedure reported in reference 2 and 3, compound 2 and compound C were synthesized respectively.

Synthesis of Tetraamine (TAm, 3)

To compound C (130 mg, 0.024 mmol) added DMF (5 mL) and potassium carbonate (0.1 g), stirred for half hour. To the above reaction mixture added 50 equiv of diethyl amine. The reaction was stirred at 55 °C for two days. The reaction mixture was cooled and diluted with dichloromethane and washed with water (4x30 mL). The organic layer was dried over Na2SO4 and evaporated to yield TAm (3). The obtained final product was dried

over vacuum at 120 °C for 2 days.

Synthesis of Tetrathiol (TT, 4)

(i) Compound C (450 mg, 0.25 mmol) and KSAc (1.48 mmol) was added in 20 mL of DMF and stirred for 8 h at RT. After this product was separated between CHCl3 and water. The

organic layer was dried over Na2SO4. The crude was purified by column chromatography

(SiO2) using CHCl3 as eluent to obtain tetra thioacetate substituted cavitand in 85% (367

mg) yield.

ESI-HRMS: Calculated for C100H80O20S4Na [M+Na]+: 1752.4023, observed: 1752.3989.

(ii) Tetra thioacetate substituted cavitand (367 mg, 0.22 mmol) was dissolved in 10 mL of dry THF. To this solution 50 mg of LiAlH4 was added in N2 atmosphere and was stirred

for 30 min at 0 oC. The reaction was monitored by TLC by using CHCl3 as eluent. After

the reaction was completed 3-4 drops of 20% HCl was added to quench the reaction. After this product was separated between CHCl3 and water. The organic layer was dried

over Na2SO4. The crude was purified by column chromatography (SiO2) using CHCl3 as

eluent to obtain TT (4) in 78% (267 mg) yield.

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Synthesis of E

(i) In 100 mL round bottom flask compound D (600 mg, 0.303 mmol) was taken and dissolved in 20 mL CHCl3 and 3-4 drops of DMA. To this solution 8 equivalent of Dess–

Martin periodinane was added followed by 0.2 mL of H2O and the reaction mixture was

stirred for 3 h. At the end of the reaction product was washed by a mixture of saturated solution of NaHCO3 and 10% Na2S2O3. The crude was purified by silica column

chromatography with CHCl3 as eluent to obtain top benzalaldehyde and bottom O-benzyl

substituted cavitand as yellow solid in 92% (550 mg) yield.

ESI-HRMS: Calculated for C124H96O24Na [M+Na]+ 1992.6218, observed: 1992.6066.

(ii) Top benzalaldehyde and bottom O-benzyl substituted cavitand (550 mg, 0.279 mmol) was dissolved in 20 mL of DMF and 8 equivalent of oxone was added to that and reaction was stirred at RT for 3 h. Then reaction mixture was filtered to remove the inorganic solid and unreacted residual oxone was quenched by adding saturated aqueous solution of Na2S2O3. The product was extracted in CHCl3 and dried in reduced pressure.

The white solid was then acidified with 2 N HCl and filtered to obtain top benzoic acid bottom and O-benzyl substituted cavitand in 79% (450 mg) yield.

(iii) Top benzoic acid and bottom O-benzyl substituted cavitand (450 mg, 0.221 mmol) was dissolved in total 50 mL of 20% MeOH in CHCl3 and to this 10 equivalent of

trimethylsilyldiazomethane was added and stirred for 1 h at RT. At the end of the reaction unreacted trimethylsilyldiazomethane and solvent was removed by reduced pressure and product was purified by silica column chromatography using CHCl3 as eluent to obtain E

as white solid in 91% (420 mg).

Synthesis of TTTA

(i) Compound E (420 mg, 0.201 mmol) was dissolved in 100 mL of freshly distilled THF and 400 mg of Pd-C was added to that in N2 atmosphere. H2 gas was bubbled through the

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S6 solution for 1 h. After that the Pd-Cwas filtered off and the product was concentrated to obtain top benzoate ester and bottom propanol substituted cavitand as white solid in 91% (370 mg) yield.

(ii) Top benzoate ester and bottom propanol substituted cavitand (340 mg, 0.196 mmol) was suspended in 50 mL CH2Cl2. To this PPh3 (8 equivalent) and CBr4 (9 equivalent) was

added and stirred at RT overnight. The solvent was distilled off and product was purified by silica column chromatography using CHCl3 as eluent to obtain top benzoate ester and

bottom bromide substituted cavitand as white solid in 92% (360 mg) yield.

ESI-HRMS: Calculated for C100H76O24Br4Na [M+Na]+ 2004.1358, observed: 2004.1272.

(iii) Top benzoate ester and bottom bromide substituted cavitand (360 mg, 0.181 mmol) was dissolved in 10 mL of DMF and to the solution 5.2 equivalent of KSAc was added and stirred overnight at RT. The product was extracted with CHCl3 from H2O partition and

dried over Na2SO4. Product was purified by silica column chromatography using CHCl3

as eluent to obtain top benzoate ester and bottom thioacetate substituted cavitand as white solid in 98% (350 mg) yield.

ESI-HRMS: Calculated for C108H88O28S4Na [M+Na]+ 1984.4270, observed: 1984.4270.

(iv) Top benzoate ester and bottom thioacetate substituted cavitand (350 mg, 0.178 mmol) was dissolved in 5 mL of DMA in a two necked round bottom flask. A KOH solution (100 equivalents) was made in H2O in a different two necked round bottom flask. Both

the solution was degassed for 15 minutes and then KOH solution was added to DMA at once and the solution was refluxed for 4 h at N2 atmosphere. Then the reaction mixture

was cooled to 0 oC and 3-4 drops of degassed 1 N HCl solution was added to the reaction mixture. Immediately the solution turned turbid and product precipitated out. The solvent was distilled off by rotatory evaporator at reduced pressure. The product was washed with H2O several times to remove acid completely through sintered crucible and dried for

2 h by water suction at room temperature. The product was further dried at 120 oC for 12 h to obtain TTTA (5) as white powder in 90% (280 mg).

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S7 ESI-HRMS: Calculated for C96H72O24S4Na [M+Na]+ 1760.3221, observed: 1760.3189.

Synthesis of G

For 20 minutes, N2 was bubbled through a suspension of A (1 g, 0.48 mmol), F (0.63 g,

2.9 mmol) and anhydrous K2CO3 (540 mg, 3.9 mmol) in pyridine (55 mL). To this CuO

(310 mg, 3.9 mmol) was added and the stirring mixture was refluxed for 8 days. Then the solvent was removed under reduced pressure. The remaining solid was added to CHCl3

and filtered on a celite bed. The filtrate was concentrated and passed through a SiO2

column using CHCl3 as eluent to obtain G as white solid in 37 % (400 mg) yield.

Synthesis of TATP (6)

N2 gas was bubbled through a suspension of G (400 mg, mmol), Pd/C (200 mg) and THF

(100 mL). Subsequently, H2 gas was purged for 2 h at RT. The reaction mixture was

filtered and the solvent removed under reduced pressure to give the product TATP (6) as a white solid in 96 % (270 mg) yield.

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Figure S1. 1H NMR spectrum of tetra thioacetate substituted cavitand in CDCl3.

Figure S2. 1H NMR spectrum of tetrathiol substituted cavitand (TT) in CDCl3. O O O _O _O O _O O O O O O O O O O

AcS AcS SAc SAc

O O O _O _O _O O _O O O O O O O _O O HS HS SH SH

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Figure S3. 1H NMR spectrum (500 MHz) of TATP (1 mM) in DMSO-d6 (‘ ’represents the residual proton resonance of water present in DMSO-d6 and ‘●’ represents the residual proton resonance of DMSO-d6 solvent).

Figure S4. 1H NMR spectrum of top benzalaldehyde and bottom O-benzyl substituted cavitand in CDCl3.

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Figure S5. 1H NMR spectrum of top benzoic acid bottom and O-benzyl substituted cavitand in DMSO-d6.

Figure S6. 1H NMR spectrum of top benzoate ester and bottom O-benzyl substituted cavitand in CDCl3.

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Figure S7. 1H NMR spectrum of top benzoate ester and bottom bromide substituted cavitand in CDCl3.

Figure S8. 1H NMR spectrum of top benzoate ester and bottom thioacetate substituted cavitand in CDCl3. OMe O O O O _O _O _O O _O O O O O O O _O O Br Br Br Br OMe O MeO O MeO O OMe O O O O _O _O _O O _O O O O O O O _O O

AcS AcS SAc SAc

OMe O MeO

O

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Figure S9. 1H NMR spectrum of top tetra acid and bottom tetrathiol substituted cavitand

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Figure S10. UV-vis spectra of TT∩AuNP (red, in CHCl3), TAm∩AuNP (black, in CHCl3) and

TTTA∩AuNP (blue, in water).

Figure S11. TEM images of (i) OAm∩AuNP immediately after preparation and (ii)

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Figure S14. Percentage volume versus hydrodynamic diameter profiles extracted from dynamic

light scattering experiments for TT∩AuNP recorded in CHCl3. The average size of the particle is

4.8 ± 2.1 nm (10 scans).

Figure S15. Percentage volume versus hydrodynamic diameter profiles extracted from dynamic

light scattering experiments for TTTA∩AuNP recorded in NaOH/H2O. The average size of the

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Figure S16. TGA traces showing weight loss with respect to temperature for TT cavitand (black)

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Figure S17. TGA traces showing weight loss with respect to temperature for TTTA cavitand

(black) and TTTA∩AuNP (red).

Figure S18. 1H NMR titration spectra of TT cavitand ([TT] = 1 mM) with bromoadamantane (7) in DMSO-d6 in 500 MHz with increment of 0.2 equivalent of guest. (i) Free bromoadamantane, (ii) free TT, (iii) TT: 7 = 1:0.2, (iv) TT: 7 = 1:0.4, (v) TT: 7 = 1:0.6, (vi) TT: 7 = 1:0.8, and (vii) TT: 7 = 1:1. Here ‘∗’ bound guest signal, ‘•’ free guest signal, ‘■’ residual DMSO and ‘▲’ residual H2O in DMSO. Various protons in 1H NMR of TT is labeled according to Scheme 1.

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Figure S19. 1H NMR titration spectra of TT cavitand ([TT] = 1 mM) with adamantaneacetic acid (9) in DMSO-d6 in 500 MHz with increment of 0.2 equivalent of guest. (i) Free

adamantaneacetic acid, (ii) free TT, (iii) TT: 9 = 1:0.2, (iv) TT: 9 = 1:0.4, (v) TT: 9 = 1:0.6, (vi) TT: 9 = 1:0.8, and (vii) TT: 9 = 1:1. Here ‘∗’ bound guest signal, ‘•’ free guest signal, ‘■’ residual DMSO and ‘▲’ residual H2O in DMSO. Various protons in 1H NMR of TT is labeled

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Figure S20. 1H NMR titration spectra of TT cavitand ([TT] = 1 mM) with adamantanethione (10) in DMSO-d6 in 500 MHz with increment of 0.2 equivalent of guest. (i) Free

adamantanethione, (ii) free TT, (iii) TT: 10 = 1:0.2, (iv) TT: 10 = 1:0.4, (v) TT: 10 = 1:0.6, (vi) TT: 10 = 1:0.8, and (vii) TT: 10 = 1:1. Here ‘∗’ bound guest signal, ‘•’ free guest signal, ‘■’ residual DMSO and ‘▲’ residual H2O in DMSO. Various protons in 1H NMR of TT is labeled

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Figure S21. 1H NMR titration spectra of TT cavitand ([TT] = 1 mM) with camphorthione (11) in DMSO-d6 in 500 MHz with increment of 0.2 equivalent of guest. (i) Free camphorthione, (ii) free TT, (iii) TT: 11 = 1:0.2, (iv) TT: 11 = 1:0.4, (v) TT: 11 = 1:0.6, (vi) TT: 11 = 1:0.8, and (vii) TT: 11 = 1:1. Here ‘∗’ bound guest signal, ‘•’ free guest signal, ‘■’ residual DMSO and ‘▲’ residual H2O in DMSO. Various protons in 1H NMR of TT is labeled according to Scheme 1.

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Figure S22. 1H NMR spectra of (i) free guest bromoadamantane (7) (ii) free host TT (1 mM) (iii) 7@TT (iv) TT∩AuNP ([cavitand] = 1 mM) (v) 7@TT∩AuNP in DMSO-d6 in 500 MHz.

Here ‘∗’ indicates bound guest signal, ‘•’ indicates free guest signal, ‘■’ indicates residual DMSO and ‘▲’ indicates residual H2O in DMSO. Various host signals are assigned according to Scheme 1.

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Figure S23. 1H NMR spectra of (i) Free guest adamantaneacetic acid (9) (ii) free host TT (1 mM) (iii) 9@TT (iv) TT∩AuNP ([cavitand] = 1 mM) (v) 9@TT∩AuNP in DMSO-d6 in 500

MHz. Here ‘∗’ indicates bound guest signal, ‘•’ indicates free guest signal, ‘■’ indicates residual DMSO and ‘▲’ indicates residual H2O in DMSO. Various host signals are assigned

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Figure S24. 1H NMR spectra of (i) Free guest adamantanethione (10) (ii) free host TT (1 mM) (iii) 10@TT (iv) TT∩AuNP ([cavitand] = 1 mM) (v) 10@TT∩AuNP in DMSO-d6 in 500 MHz.

Here ‘∗’ indicates bound guest signal, ‘•’ indicates free guest signal, ‘■’ indicates residual DMSO and ‘▲’ indicates residual H2O in DMSO. Various host signals are assigned according to Scheme 1.

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Figure S25. 1H NMR spectra of (i) Free guest camphorthione (11) (ii) free host TT (1 mM) (iii) camphorthione @TT (iv) TT∩AuNP ([cavitand] = 1 mM) (v) 11@TT∩AuNP in DMSO-d6 in

500 MHz. Here ‘∗’ indicates bound guest signal, ‘•’ indicates free guest signal, ‘■’ indicates residual DMSO and ‘▲’ indicates residual H2O in DMSO. Various host signals are assigned

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Figure S26. Representative isothermal titration calorimetry data of 7@TT complex at 25 oC in water. Power applied as a function of time (left) and integrated enthalpy plotted against number of injections (right).

Figure S27. Representative isothermal titration calorimetry data of 7@TT∩AuNP complex at 25 o

C in water. Power applied as a function of time (left) and integrated enthalpy plotted against number of injections (right).

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Figure S29. Representative isothermal titration calorimetry data of 8@TT∩AuNP complex at 25 o

C in water. Power applied as a function of time (left) and integrated enthalpy plotted against number of injections (right).

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Figure S31. Representative isothermal titration calorimetry data of 10@TT∩AuNP complex at

25 oC in water. Power applied as a function of time (left) and integrated enthalpy plotted against number of injections (right).

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Figure S33. Representative isothermal titration calorimetry data of 11@TT∩AuNP complex at

25 oC in water. Power applied as a function of time (left) and integrated enthalpy plotted against number of injections (right).

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Figure S34. 1H NMR titration spectra of TTTA (5, 1 mM in 20 mM NaOD/D2O) with

bromoadamantane (7). (i) TTTA (ii) 0.5 equiv of 7 (iii) 1 equiv of 7. Here bound guest signal and residual water present in the D2O solvent are denoted by ‘∗’ and ‘•’ respectively.

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adamantaneacetic acid (9). (i) TTTA (ii) added 0.5 equiv of 9 (iii) added 1 equiv of 9. Here bound guest signal and residual water present in the D2O solvent are denoted by ‘∗’ and ‘•’

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hexyladamantanoate (12). (i) TTTA (ii) added 0.25 equiv of 12 (iii) added 0.5 equiv of 12. Here bound guest signal and residual water present in the D2O solvent are denoted by ‘∗’ and ‘•’

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dimethylbenzil (13). (i) TTTA (ii) added 0.25 equiv of 13 (iii) added 0.5 equiv of 13. Here bound guest signal and residual water present in the D2O solvent are denoted by ‘∗’ and ‘•’

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Figure S38. 1H NMR spectra (500 MHz) of (i) TTTA∩AuNP, (ii) 12: (TTTA∩AuNP) = 0.33:1, (iii) 12: (TTTA∩AuNP) = 1:1, (iv) added TATP of 0.25 equiv to the (iii) solution, (v) added TATP of 1 equiv to the (iii) solution, and (vi) 12@TATP2. Various hydrogens of host TATP and

guest 12 are indicated according to Scheme 1. Broad and weak signals for 12@(TTTA∩AuNP )2

are indicated with ‘∗’. Signals assigned by β2 and β1 are from homocomplex of 12@(TATP)2

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Figure S39. Partial 1H NMR spectra (500 MHz) of (i) 12: TTTA∩AuNP = 0.33:1, (ii)

12@TATP2, and (iii) added TATP of 1 equiv to the solution of 12: TTTA∩AuNP =1:1. Various

hydrogens of host TATP and guest 12 are indicated according to Scheme 1. Broad and weak signals for 12@(TTTA∩AuNP)2 are indicated with ‘∗’. Signals assigned by β1 and β2 are guest

signals from homocomplex and β′1, β′2 are from hetero-complexes. Residual water present in the

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Figure S40. 1H NMR spectra of (i) 12@TTTA2 (host: guest = 2:1), (ii) 12@TATP2 (host: guest

= 2:1), and (iii) 12@(TATP.TTTA) (TATP: TTTA: guest = 1:1:1).

Figure S41. 1H NMR spectra of (i) 13@TTTA2 (host: guest = 2:1), (ii) 13@TATP2 (host: guest

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References

1. Gibb, C. L. D.; Gibb, B. C., Well-Defined, Organic Nanoenvironments in Water: The Hydrophobic Effect Drives a Capsular Assembly. J. Am. Chem. Soc. 2004, 126, 11408-11409.

2. Kulasekharan, R.; Ramamurthy, V., New Water-Soluble Organic Capsules Are Effective in Controlling Excited-State Processes of Guest Molecules. Org. Lett. 2011, 13, 5092-5095.

3. Ramasamy, E.; Jayaraj, N.; Porel, M.; Ramamurthy, V., Excited State Chemistry of Capsular Assemblies in Aqueous Solution and on Silica Surfaces. Langmuir 2011, 28, 10-16.