Gold Nanoparticle-supported Transition Metal Complexes as Hybrid Catalysts and MRI Contrast Agents...
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- Slide 1
- Gold Nanoparticle-supported Transition Metal Complexes as
Hybrid Catalysts and MRI Contrast Agents : : 1
- Slide 2
- 2 Hydrogen Nuclei Alignment to the External Field Chem. Soc.
Rev., 2012,41, 2575
- Slide 3
- 3 MRI Measurement Step 1: Place Subject in a Big Magnet When
you put any material in an MRI scanner, the protons align with the
direction of the magnetic field. Chem. Soc. Rev., 2012,41,
2575
- Slide 4
- 4 M xy = M * e -t/T2 M z = M * ( 1 - e -t/T1 ) T2 T1 Step 2:
Apply Radio Waves Chem. Soc. Rev., 2012,41, 2575 recovers to 63%
decays back to 37%
- Slide 5
- 5 Step 3: Measure Emitted Radio Waves T 1 = time constant of
how quickly the Hs realign with the magnetic field T 2 = time
constant of how quickly the Hs emit energy when recovering to
equilibrium fat has high signal bright CSF has low signal dark
T1-WEIGHTED ANATOMICAL IMAGET2-WEIGHTED ANATOMICAL IMAGE fat has
low signal dark CSF has high signal bright CSF: Cerebrospinal fluid
Med. Phys. 1984,11,425
- Slide 6
- 6 Contrast Agents for Clinical MRI (T 1 ) Invest. Radiol. 1993,
28, 521. T 1 contrast agents: Gd-DTPA, Gd-DOTA, Gd-oxalate increase
signals by decreasing the T 1 of protons
- Slide 7
- 7 Contrast Agents for Clinical Animal MRI (T 2 ) T 2 contrast
agents: Superparamagnetic Iron Oxide (SPIO) causing a shortening of
T 2 and decreasing signal intensity on T 2 weight imaging J. Am.
Chem. Soc. 2005, 127, 12387-12391 pre- injection immediate -post 1
hr4 hr12 hr top: grayscale map bottom: color map Fe 3 O 4 (9
nm)
- Slide 8
- Dose DecreaseMetabolic Rate IncreaseBiocompatibilityContrast
Enhancement Chelates Biovehicles ParamagnetismStructure Progress of
MRI Contrast Agents 8
- Slide 9
- 9 Au NPs with controllable solubility soluble metal complex
functional groups coordinating ligands space linker Contrast Agents
Design Au nanoparticles ( Au NPs) have been known not only to
possess solid surfaces resembling the (1 1 1) surface of bulk gold
but also to behave like soluble molecules for their dissolvability,
precipitability, and redissolvability. Lin, Y.-Y; Tsai, S.-C.; Yu,
S. J. J. Org. Chem. 2008, 73, 4920-4928.
- Slide 10
- Space Linker HS(CH 2 ) 11 N(H)P(O)(2-Py) 2 (L1) dissolved in
organic solventsdissolved in water DO3A-SH (L2) Contrast Agents
Design Ni complexes Mn complexes Gd complexes 10 L1 L2 M = Ni 2+ Mn
2+ M = Gd 3+
- Slide 11
- Synthesis of L1 11 Lin, Y.-Y; Tsai, S.-C.; Yu, S. J. J. Org.
Chem. 2008, 73, 4920-4928.
- Slide 12
- 12 Synthesis of RS-Au-L1-M n+ 3.77 nm 0.88 2.53 0.4 nm
- Slide 13
- EPR Spectra of Mn Complexes [Mn(bpy)( -Cl) 2 ] n g - factor 2
Inorg. Chim. Acta, 2005, 358, 44594465 13 [CH 3 (CH 2 ) 3
N(H)P(O)(2-Py) 2 ]MnCl 2 (Mn4C)
- Slide 14
- 14 Mn 2+ 2p 3/2 = 639 eV Mn 2+ 2p 1/2 = 651 eV XPS Spectra of
Mn Complexes satellite Physical Review B 1991, 43, 11971
- Slide 15
- 15 IR Spectra of Mn Complexes
- Slide 16
- Hydrodynamic size (DLS) : 167 50 nm Au Mn TEM Images and EDS
Spectrum of RS-Au-L1-MnCl 2 2.53 nm 0.4 16
- Slide 17
- J. Polym. Sci., Part A: Polym. Chem. 2011, 49, 3464 Tetrahedron
Lett. 2011, 52, 2058. Synthesis of L2 17
- Slide 18
- Synthesis of L2 18 78 %
- Slide 19
- Synthesis of RS-Au-DO3A-Gd 19 60 % 3.09 nm 0.52 2.99 nm
0.45
- Slide 20
- 20 1 H NMR Spectrum of Au-SR, DO3ASH and RS-Au-DO3A L2
RS-AuDO3A
- Slide 21
- EPR Spectra of Gd Complexes GdDO3A 21 g factor = 1.998 J. Am.
Chem. Soc. 2001, 123, 2637-2644 [Gd(H 2 O) 8 ] 3+
- Slide 22
- Gd 3+ 3d 3/2 = 1220 eV Gd 3+ 3d 5/2 = 1185 eV satellite XPS and
IR Spectra of Gd Complexes 22
- Slide 23
- 2.99 nm 0.4 Au Gd TEM Images and EDS Spectrum of RS-Au-DO3A-Gd
23
- Slide 24
- 24 Quantification of Paramagnetic Metal Complexes Flame atomic
absorption spectrometry, FLAA ) Inductively coupled argon plasma
optical emission spectrometry ICP-OES ) ( Graphite-furnace atomic
absorption spectrometry, GFAA ) ( Inductively coupled plasma mass
spectrometry, ICP-MS ) RS-Au-L-MnCl 2 1.42 10 -6 mol Mn 1 ppm 0.32
mg RS-Au-L-MnCl 2 in 25 mL solvent RS-Au-DO3A-Gd 3.5 10 -7 mol Gd
380 ppm 172 mg RS-Au-DO3A-Gd in 25 mL solvent
- Slide 25
- 25 Dynamic Motion between Solvent and Paramagnetic Metal
Complexes Chem. Soc. Rev., 2010, 39, 51-60
- Slide 26
- Concentration Dependent T 1 and R 1 Influenced by Ni 2+
Complexes 26 Ni11C Au@Ni Ni4C r 1 = relaxivity P M : q: 1M : M :
(exchange time) R1R1
- Slide 27
- The Hydroxyl Proton Relaxation Rates Influenced by Ni 2+
Complexes 27 [Ni 2+ ] (mM)T 1 (s)T 1 error (s)R 1 (s -1 )
100.1350.0047.401 50.2420.0064.132 30.4190.0042.386
1.50.7390.0171.353 0.91.0860.0350.920 0.51.5210.0500.657 [Ni 2+ ]
(mM)T 1 (s)T 1 error (s)R 1 (s -1 ) 100.1480.0086.756
50.3340.0102.994 30.4670.0182.141 1.51.0080.0560.992
0.91.3620.0480.733 0.51.9070.0570.524 Au@Ni r 1 (s -1 mM -1 ) =
0.933 Ni11C r 1 (s -1 mM -1 ) = 0.752 [Ni 2+ ] (mM)T 1 (s)T 1 error
(s)R 1 (s -1 ) 100.1890.0065.291 50.3360.0102.976 30.5140.0131.946
1.50.8790.0171.138 0.91.1680.0220.856 0.51.6760.0360.597 Ni4C r 1
(s -1 mM -1 ) = 0.779 The relaxation rate of Ni 2+ is slightly
enhanced upon immobilization onto AuNPs. Methanol T 1MeOH = 6.622 s
R 1 = 0.151 s -1 r 1 = 3.87 *10 -3 s -1 mM -1
- Slide 28
- Sample r 1OH (s -1 mM -1 )r 1CH3 (s -1 mM -1 ) MnCl 2 19.85
0.865.10 0.20 Mn4C16.58 0.573.99 0.08 Mn11C18.23 0.634.61 0.23 MnCl
2 Mn4C Mn11C Relaxivity of Molecular Mn Complexes at 298K 298K Bulk
methanol Chemical exchange Bound methanol 28
- Slide 29
- Sample Mn 2+ loading (ppm/mg) r 1OH (s -1 mM -1 )r 1CH3 (s -1
mM -1 ) Au@Mn-5v11.8218.30 0.595.20 0.04 Au@Mn-5v22.5719.81
0.315.04 0.05 Au@Mn-5v43.2620.95 0.185.73 0.01 Au@Mn-5v64.6921.66
0.385.42 0.10 Relaxivity of Au-L1-Mn Complexes at 298K 29 Weight
ratio Au : L = 5:1 (Au@Mn-5v1) Au : L = 5:2 (Au@Mn-5v2) Au : L =
5:4 (Au@Mn-5v4) Au : L = 5:6 (Au@Mn-5v6)
- Slide 30
- Relaxivity of Mn 2+ in Various Forms at 298K 30
- Slide 31
- 31 MRI of Mn Complexes in MeOH Background tau 400 ms500 ms600
ms700 ms 800 ms900 ms1 s FOV : 3.6 x 3.6 x 0.1 cm MeOH Mn4C MnCl 2
RS-Au-L-MnCl 2 (inversion recovery)
- Slide 32
- Temperature : 228 K ~ 308 K Temperature Dependent Relaxivity of
Mn Complexes 32 T 1MeOH = 6.622 s T 1Mncl2 = 0.037 s (r 1 : 26.81
mM -1 s -1 ) Au@Mn-5v4: 0.035 s (r 1 : 28.49 mM -1 s -1 ) Au@Mn
5v1: 0.044 s (r 1 : 22.65 mM -1 s -1 )
- Slide 33
- 33 Nuclear Magnetic Relaxation Dispersion (NMRD) profile of Gd
complexes under Difference Temperature Dalton Transactions 2012,
41, 5472. 25 C (), and 37 C ( ).
- Slide 34
- 34 Pure water at 1.5 T : 3 s GdCl 3 at 82 MHz: 0.09 s (r 1 :
10.51 mM -1 s -1 ) GdDO3A: 0.10 s (r 1 :9.60 mM -1 s -1 )
RS-Au-DO3A-Gd: 0.09s (r 1 :11.01 mM -1 s -1 ) Gd-DTPA: 0.2s (r 1
:5.01 mM -1 s -1 ) Nuclear Magnetic Relaxation Dispersion (NMRD)
profile of Gd complexes GdDO3A
- Slide 35
- 35 Hydrodynamic size (DLS) : 167 50 nm
- Slide 36
- 36 Proposed Mechanism for RS-Au-DO3A Gd Aggregation P M : q: 1M
: M : (exchange time) R1R1 Hydrodynamic size (DLS) : 161 nm 73
- Slide 37
- Acetylation of Alcohol Application : 1. protective agent 2.
medicine synthesis, ex: aspirin 3. protein acetylation 37
- Slide 38
- 38 Acetylation of Alcohol Tetrahedron Lett. 2008, 49, 3165
- Slide 39
- 39 Substrates of Acetylation GdDO3A (Cat. 1) RS-Au-DO3A-Gd
(Cat. 2)
- Slide 40
- 40 Cat. 1 Catalyzed Acetylation Reactions of ROH with Acetic
Anhydride
- Slide 41
- 41 Cat. 1 Catalyzed Acetylation Reactions of ROH with Acetic
Anhydride
- Slide 42
- 42 Cat.1 and Cat.2 Catalyzed Acetylation Reactions of ROH with
Acetic Anhydride under MW Irradiation
- Slide 43
- 43 Cat.1 and Cat.2 Catalyzed Acetylation Reactions of ROH with
Acetic Anhydride under MW Irradiation
- Slide 44
- 44 Recycling of Cat. 2 in Acetylation Reactions of Phenol with
Acetic Anhydride
- Slide 45
- 45 Proposed Mechanism for Acetylation of Alcohols Org.
Lett.1999, 1, 1985.
- Slide 46
- 46 Conclusions 1.We have developed a methodology to
successfully immobilize molecular Mn(II) and Gd(III) complexes onto
surfaces of Au NPs. Their structures were characterized by using 1
H NMR, IR, TEM, AAS, ICP-AES, EPR and XPS spectroscopy. 2.The
relaxivity of RS-Au-L-M + NPs (M = Ni 2+, Mn 2+ ) in methanol is as
expected to be greater than that of the molecular complexes. 3. We
have synthesized water soluble RS-Au-DO3A-Gd NPs. These NPs were
found to exhibit excellent T 1 -shortening effect in MRI. 4.We have
successfully demonstrated the catalytic activity of the Gd(III)
complexes for acetylation of alcohol with acetic anhydride 5.
Further acceleration on the rate of the Gd (III) complexescatalyzed
acetylation of alcohols can be achieved under microwave irradiation
conditions. 6. The RS-Au-DO3A-Gd NPs can be effectively recycled
throughout eight cycle under microwave irradiation
- Slide 47
- 47 Acknowledge : : :
- Slide 48
- 48 Acknowledge
- Slide 49
- 49 Acknowledge
- Slide 50
- 50 10~50 nm 100~200 nm
- Slide 51
- 51 Integration of the 1 H NMR signals of phenyl acetate
(iodoanisole as internal standard) gave 97.9% NMR yields (0.538
mmol), while GC analysis on the same sample gave 99% GC yields
(0.544 mmol).
- Slide 52
- 52 1 mM Mn 2+ : RS-Au-L-MnCl 2 1.42 10 -6 mol Mn 25 mL solvent,
17.6 mg RS-Au-L-MnCl 2 1 mM Gd 3+ : RS-Au-DO3A-Gd 3.5 10 -7 mol Gd
25 mL solvent, 71.4 mg RS-Au-DO3A-Gd
- Slide 53
- 53 S1 Gd1 : 1.238 nm S1 C15 : 0.961 nm
- Slide 54
- 54 C14 Mn2 : 0.89 nm N3 Mn2 : 0.45 nm
- Slide 55
- 55 ICP-OES: ICP-Mass: , HR-ICP-Mass:
- Slide 56
- 56 90 degree RF Relaxation Z-axis , Z , , (phase), , dephase
Z-axis x-axis