1. A method for the manufacture of monodisperse iron oxide nanoparticles having a core size of less than 10 nm and being coated with poly(ethylene glycol) comprising the steps of:
a. synthesizing
i. the iron oxide nanoparticles and poly(ethylene glycol) based ligands with phosphate anchor groups by mixing poly(ethylene glycol) methyl ether with an excess of POCh and subsequent hydrolysis of the remaining two P-CI groups; and
ii. coating the iron oxide nanoparticles with the poly(ethylene glycol) by mixing the nanoparticles with a large excess of poly(ethylene glycol); and
c. transferring the coated iron oxide nanoparticles into an aqueous environment.
2. The method of claim 1, wherein the iron oxide nanoparticles have core sizes between 4 to 6 nm.
3. The method of claim 2, using a mixture of iron oxide nanoparticles with a defined ratio of nanoparticles with a core size between 4 and 6 nm.
4. The method according to claim 1, wherein for synthesizing the iron oxide nanoparticles an iron precursor, a reduction agent, stabilizer and a first solvent are mixed to form a black solution and heated followed by separating the black solution from the first solvent by a precipitation step by adding an alcohol and centrifugation with subsequent re-dispersion in a solvent and repeating the precipitation step before final dispersing in a second solvent.
5. The method according to claim 4, wherein phenyl ether is used as the first solvent in the mixture for synthesis of the iron oxide cores with 4 nm diameter and benzyl ether for the synthesis of the iron oxide cores with 6 nm diameter.
6. The method according to claim 1, wherein the iron oxide nanoparticles are oleic acids stabilized superparamagnetic nanoparticles.
7. The method according to claim 1, wherein the coating of the iron oxide nanoparticles comprises heating to 60\xb0 C.
8. The method according to claim 1, wherein the coated iron oxide nanoparticles are transferred from tetrahydrofurane into an aqueous environment
9. The method according to claim 1, wherein the poly(ethylene glycol) chain length is adjusted by using a poly(ethylene glycol) with a molecular mass in the range of 400 to 2000 gmol, preferably with a minimum chain length of about 550 gmol, and most preferably with a chain length of 1100 gmol.
10. The method according to claim 1 wherein the iron oxide is magnetite.
11. A nanoparticle comprising a iron oxide core with a diameter in the range of 4 to 6 nm coated with a poly(ethylene glycol) polymer via a phosphate anchor.
12. The nanoparticle of claim 11 having a hydrodynamic diameter in the range of 10 to 15 nm.
13. The nanoparticle of claim 11, wherein a chain length of the poly(ethylene glycol) polymer is adjusted by using a poly(ethylene glycol) polymer with a minimum molecular mass of about 550 gmol, and preferably 1100 gmol.
14. The nanoparticle according to claim 11, wherein the longitudinal relaxivity r1 is in the range from 7.3 to 13 mM\u22121s\u22121 and the r2r1 ratio is in the range from 2.4 to 3.2 at 1.41 T.
15. A composition comprising a nanoparticle according to claim 11.
16. The composition of claim 15 further comprising physiologically tolerable carrier or stabilizer.
17. The use of a nanoparticle manufactured according to the method of claim 1 as one of a contrast agent, a blood pool contrast enhancement (T1) agent, lymph node imaging agent, targeting imaging agent and hyperthermia agent.
18. The use of a nanoparticle resulting from the method of claim 1 for the manufacture of a contrast agent or contrast agent composition.
19. The use of a nanoparticle resulting from the method of claim 1 in the prophylaxis, diagnosis, therapy, follow-up andor aftercare of a therapy.
20. The use of a nanoparticle resulting from the method of claim 1 in imaging methods.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A halo-functional silane possessing halogen functionality and alkanedioxysilyl functionality, and partial hydrolyzates thereof, said halo-functional silane being selected from the group consisting of:
2-2-(4-chloromethyl-phenyl)-ethyl-2,5-dimethyl-1,3,2dioxasilinane, 2-2-(4-chloromethyl-phenyl)-ethyl-2-methoxy-5-methyl-1,3,2dioxasilinane, 2-2-(4-bromomethyl-phenyl)-ethyl-2-ethoxy-5-methyl-1,3,2dioxasilinane, 2-ethoxy-2-2-(4-iodomethyl-phenyl)-ethyl-5-methyl-1,3,2dioxasilinane, 2-2-(4-chloromethyl-phenyl)-ethyl-2-ethoxy-5-methyl-1,3,2dioxasilinane, 2-2-(4-chloromethyl-phenyl)-propyl-2-ethoxy-5-methyl-1,3,2dioxasilinane, 2-{2-4-(1-chloro-ethyl)-phenyl-propyl}-2-ethoxy-5-methyl-1,3,2dioxasilinane, 2-{2-4-(1-chloro-ethyl)-phenyl-propyl}-2-ethoxy-4-methyl-1,3,2dioxasilinane, 2-2-(4-chloromethyl-phenyl)-ethyl-2-ethoxy-4-methyl-1,3,2dioxasilinane, 2-2-(4-chloromethyl-phenyl)-ethyl-2-ethoxy-4,4,6-trimethyl-1,3,2dioxasilinane, 2-2-(4-chloromethyl-phenyl)-ethyl-2-ethoxy-1,3,2dioxasilinane, 2-2-(4-chloromethyl-phenyl)-ethyl-2-ethoxy-1,3,2dioxasilolane, 3-{2-2-(4-chloromethyl-phenyl)-ethyl-5-methyl-1,3,2dioxasilinan-2-yloxy}-2-methyl-propan-1-ol, 3-{2-2-(3,4-bis-chloromethyl-phenyl)-ethyl-5-methyl-1,3,2dioxasilinan-2-yloxy}-2-methyl-propan-1-ol, 3-2-(3-chloro-propenyl)-5-methyl-1,3,2dioxasilinan-2-yloxy-2-methyl-propan-1-ol, 2-(3-chloro-propenyl)-2-ethoxy-5-methyl-1,3,2dioxasilinane, 2-(3-chloro-prop-1-ynyl)-2-ethoxy-5-methyl-1,3,2dioxasilinane, 2-(3-chloro-prop-1-ynyl)-2-ethoxy-4,4,6-trimethyl-1,3,2dioxasilinane, 2-(3-chloro-but-1-ynyl)-2-ethoxy-4,4,6-trimethyl-1,3,2dioxasilinane, 2-2-(4-chloromethyl-cyclohexyl)-ethyl-2-ethoxy-4,4,6-trimethyl-1,3,2dioxasilinane, 2-2-(4-chloromethyl-cyclohex-3-enyl)-ethyl-2-ethoxy-4,4,6-trimethyl-1,3,2dioxasilinane, 2-(6-chloro-hex-4-enyl)-2-ethoxy-5-methyl-1,3,2dioxasilinane, 2-(6-chloro-4-methyl-hex-4-enyl)-2-ethoxy-5-methyl-1,3,2dioxasilinane, {2-2-(4-chloromethyl-phenyl)-ethyl-2-ethoxy-1,3,2dioxasilinan-5-yl}-methanol, {2-2-(4-chloromethyl-phenyl)-ethyl-2-ethoxy-5-ethyl-1,3,2dioxasilinan-5-yl}-methanol and mixtures thereof.
2. A halo-functional silane possessing halogen functionality and alkanedioxysilyl functionality, and partial hydrolyzates thereof, said halo-functional silane being selected from the group consisting of:
2-2-(4-chloromethyl-phenyl)-ethyl-2-(3-{2-2-(4-chloromethyl-phenyl)-ethyl-1,3,2dioxasilinan-2-yloxy}-2-methyl-propoxy)-5-methyl-1,3,2dioxasilinane, 242-(4-chloromethyl-phenyl)-ethyl-2-(3-{2-2-(4-chloromethyl-phenyl)-ethyl-5-methyl-1,3,2dioxasilinan-2-yloxy}-2-methyl-propoxy)-5-methyl-1,3,2dioxasilinane, 2-2-(4-chloromethyl-phenyl)-ethyl-2-(3-{2-2-(4-chloromethyl-phenyl)-ethyl-4,4,6-trimethyl-1,3,2dioxasilinan-2-yloxy}-1,3-dimethyl-butoxy)-4,4,6-trimethyl-1,3,2dioxasilinane, 2-2-(4-chloromethyl-phenyl)-ethyl-2-(3-{2-2-(4-chloromethyl-phenyl)-ethyl-1,3,2dioxasilinan-2-yloxy}-1,3-dimethyl-butoxy)-4,4,6-trimethyl-1,3,2dioxasilinane, 2-2-(4-chloromethyl-phenyl)-ethyl-2-(3-{2-2-(4-chloromethyl-phenyl)-ethyl-1,3,2dioxasilinan-2-yloxy}-1-methyl-propoxy)-4-methyl-1,3,2dioxasilinane, 2-2-(4-bromomethyl-phenyl)-ethyl-2-(3-{2-2-(4-bromomethyl-phenyl)-ethyl-1,3,2dioxasilinan-2-yloxy}-2-methyl-propoxy)-5-methyl-1,3,2dioxasilinane, 2-{2-4-(1-chloro-ethyl)-phenyl-propyl}-2-3-(2-{2-4-(1-chloro-ethyl)-phenyl-propyl}-1,3,2dioxasilinan-2-yloxy)-2-methyl-propoxy-5-methyl-1,3,2dioxasilinane, 2-{2-4-(1-chloro-ethyl)-phenyl-propyl}-2-3-({2-4-(1-chloro-ethyl)-phenyl-propyl}-ethoxy-methyl-silanyloxy)-2-methyl-propoxy-5-methyl-1,3,2dioxasilinane, 2-{2-4-(1-chloro-ethyl)-phenyl-propyl}-2-3-({2-4-(1-chloro-ethyl)-phenyl-propyl}-diethoxy-silanyloxy)-2-methyl-propoxy-5-methyl-1,3,2dioxasilinane, 1-2-({3-(7-chloro-hept-5-enyl)-diethoxy-silanyloxy-propoxy}-diethoxy-silanyl)-ethyl-4-chloromethyl-benzene, 1-2-({3-(7-chloro-hept-5-enyl)-ethoxy-methyl-silanyloxy-propoxy}-ethoxy-methyl-silanyl)-ethyl-4-chloromethyl-benzene, 1-chloro-7-({3-(7-chloro-hept-5-enyl)-ethoxy-methyl-silanyloxy-propoxy}-ethoxy-methyl-silanyl)-hept-2-ene, 3-chloro-1-({3-(3-chloro-propenyl)-ethoxy-methyl-silanyloxy-propoxy}-ethoxy-methyl-silanyl)-propene, 3-chloro-1-({3-(3-chloro-propenyl)-diethoxy-silanyloxy-propoxy}-diethoxy-silanyl)-propene, 2-(3-chloro-propenyl)-2-{3-(3-chloro-propenyl)-ethoxy-methyl-silanyloxy-2-methyl-propoxy-5-methyl-1,3,2dioxasilinane, 2-(3-chloro-propenyl)-2-{3-(3-chloro-propenyl)-diethoxy-silanyloxy-2-methyl-propoxy-5-methyl-1,3,2dioxasilinane, 2-(3-chloro-propenyl)-2-3-((3-chloro-propenyl)-{3(3-chloro-propenyl)-ethoxy-methyl-silanyloxy-2-methyl-propoxy-methyl-silanyloxy)-2-methyl-propoxy-5-methyl-1,3,2dioxasilinane, 2-(3-chloro-propenyl)-2-3-((3-chloro-propenyl)-{3-(3-chloro-propenyl)-diethoxy-silanyloxy-2-methyl-propoxy-ethoxy-silanyloxy)-2-methyl-propoxy-5-methyl-1,3,2dioxasilinane, 2-2-(4-chloromethyl-phenyl)-ethyl-2-{3-2-(4-chloromethyl-phenyl)-ethyl-(3-{2-(4-chloromethyl-phenyl)-ethyl-ethoxy-methyl-silanyloxy}-2-methyl-propoxy)-methyl-silanyloxy-2-methyl-propoxy}-5-methyl-1,3,2dioxasilinane, 2-2-(4-chloromethyl-phenyl)-ethyl-2-{3-2-(4-chloromethyl-phenyl)-ethyl-(3-{2-(4-chloromethyl-phenyl)-ethyl-hydroxy-silanyloxy}-2-methyl-propoxy)-ethoxy-silanyloxy-2-methyl-propoxy}-5-methyl-1,3,2dioxasilinane, 2-2-(4-chloromethyl-phenyl)-ethyl-2-{3-2-(4-chloromethyl-phenyl)-ethyl-(3-{2-(4-chloromethyl-phenyl)-ethyl-ethoxy-methyl-silanyloxy}-1,3-dimethyl-butoxy)-methyl-silanyloxy-propoxy}-4,4,6-trimethyl-1,3,2dioxasilinane, and mixtures thereof.
3. A rubber composition comprising:
(a) at least one rubber component;
(b) at least one silane-reactive filler; and
(c) at least one halo-functional silane of claim 1 andor partial hydrolyzate thereof.
4. A rubber composition comprising:
(a) at least one rubber component;
(b) at least one silane-reactive filler;
(c) at least one halo-functional silane of claim 1 andor partial hydrolyzate thereof; and,
(d) at least one activating agent.
5. The cured rubber composition of claim 3.
6. The cured rubber composition of claim 4.
7. A tire, tire component, a shoe sole, a hose, a seal, a cable jacket, a gasket or an industrial good containing the cured rubber composition of claim 5.
8. A tire, tire component, a shoe sole, a hose, a seal, a cable jacket, a gasket or an industrial good containing the cured rubber composition of claim 4.
9. A composition comprising:
(a) a silane-reactive filler; and
(b) at least one halo-functional silane of claim 1 andor partial hydrolyzate thereof in admixture with, or chemically bonded to, the filler of component (a).
10. The composition of claim 9, wherein the silane-reactive filler (a) is at least one selected from the group consisting of silica, titanium dioxide, aluminosilicate, alumina and siliceous materials, and combinations thereof.
11. The rubber composition of claim 3, wherein the silane (c) is pre-mixed or pre-reacted with the silane-reactive filler (b).
12. The rubber composition of claim 11, wherein the silane-reactive filler (b) is at least one selected from the group consisting of silica, titanium dioxide, aluminosilicate, alumina and siliceous materials, and combinations thereof.
13. The rubber composition of claim 4 wherein the activating agent is a transition metal salt.
14. The halo-functional silane of claim 1, andor partial hydrolyzate thereof, wherein the said halo-functional silane is selected from the group consisting of:
2-2-(4-chloromethyl-phenyl)-ethyl-2,5-dimethyl-1,3,2dioxasilinane, 2-2-(4-chloromethyl-phenyl)-ethyl-2-methoxy-5-methyl-1,3,2dioxasilinane, 2-2-(4-chloromethyl-phenyl)-ethyl-2-ethoxy-5-methyl-1,3,2dioxasilinane, 2-2-(4-chloromethyl-phenyl)-propyl-2-ethoxy-5-methyl-1,3,2dioxasilinane, 2-{2-4-(1-chloro-ethyl)-phenyl-propyl}-2-ethoxy-5-methyl-1,3,2dioxasilinane, 2-{2-4-(1-chloro-ethyl)-phenyl-propyl}-2-ethoxy-4-methyl-1,3,2dioxasilinane, 242-(4-chloromethyl-phenyl)-ethyl-2-ethoxy-4-methyl-1,3,2dioxasilinane, 242-(4-chloromethyl-phenyl)-ethyl-2-ethoxy-4,4,6-trimethyl-1,3,2dioxasilinane, 242-(4-chloromethyl-phenyl)-ethyl-2-ethoxy-1,3,2dioxasilinane, 24214-chloromethyl-phenyl)-ethyl-2-ethoxy-1,3,2dioxasilolane, 3-(22-(4-chloromethyl-phenyl)-ethyl-5-methyl-1,3,2dioxasilinan-2-yloxy}-2-methyl-propan-1-ol, 3-(242-(3,4-bis-chloromethyl-phenyl)-ethyl-5-methyl-1,3,2dioxasilinan-2-yloxy}-2-methyl-propan-1-ol, and mixtures thereof.
15. The halo-functional silane of claim 2, andor partial hydrolyzate thereof, wherein the said halo-functional silane is selected from the group consisting of:
2-2-(4-chloromethyl-phenyl)-ethyl-2-(3-{2-2-(4-chloromethyl-phenyl)-ethyl-5-methyl-1,3,2dioxasilinan-2-yloxy}-2-methyl-propoxy)-5-methyl-1,3,2dioxasilinane, 2-2-(4-chloromethyl-phenyl)-ethyl-2-(3-{2-2-(4-chloromethyl-phenyl)-ethyl-4,4,6trimethyl-1,3,2dioxasilinan-2-yloxy}-1,3-dimethyl-butoxy)-4,4,6-trimethyl-1,3,2dioxasilinane, 2-2-(4-chloromethyl-phenyl)-ethyl-2-(3-{2-2-(4-chloromethyl-phenyl)-ethyl-1,3,2dioxasilinan-2-yloxy}-1,3-dimethyl-butoxy)-4,4,6-trimethyl-1,3,2dioxasilinane, 2-2-(4-chloromethyl-phenyl)-ethyl-2-(3-{2-2-(4-chloromethyl-phenyl)-ethyl-1,3,2dioxasilinan-2-yloxy}-1-methyl-propoxy)-4-methyl-1,3,2dioxasilinane, 2-{2-4-(1-chloro-ethyl)-phenyl-propyl}-2-3-(2-{2-4-(1-chloro-ethyl)-phenyl-propyl}-1,3,2dioxasilinan-2-yloxy)-2-methyl-propoxy-5-methyl-1,3,2dioxasilinane, 2-{2-4-(1-chloro-ethyl)-phenyl-propyl}-2-3-({2-4-(1-chloro-ethyl)-phenyl-propyl}-ethoxy-methyl-silanyloxy)-2-methyl-propoxy-5-methyl-1,3,2dioxasilinane, 2-{2-4-(1-chloro-ethyl)-phenyl-propyl}-2-3-({2-4-(1-chloro-ethyl)-phenyl-propyl}-diethoxy-silanyloxy)-2-methyl-propoxy-5-methyl-1,3,2dioxasilinane, 2-2-(4-chloromethyl-phenyl)-ethyl-2-{3-2-(4-chloromethyl-phenyl)-ethyl-(3-{2-(4-chloromethyl-phenyl)-ethyl-ethoxy-methyl-silanyloxy}-2-methyl-propoxy)-methyl-silanyloxy-2-methyl-propoxy}-5-methyl-1,3,2dioxasilinane, 2-2-(4-chloromethyl-phenyl)-ethyl-2-{3-2-(4-chloromethyl-phenyl)-ethyl-(3-{2-(4-chloromethyl-phenyl)-ethyl-ethoxy-methyl-silanyloxy}-1,3-dimethyl-butoxy)-methyl-silanyloxy-propoxy}-4,4,6-trimethyl-1,3,2dioxasilinane, and mixtures thereof.
16. A rubber composition comprising:
(a) at least one rubber component;
(b) at least one silane-reactive filler; and
(c) at least one halo-functional silane of claim 2 andor partial hydrolyzate thereof.
17. A rubber composition comprising:
(a) at least one rubber component;
(b) at least one silane-reactive filler;
(c) at least one halo-functional silane of claim 2 andor partial hydrolyzate thereof; and,
(d) at least one activating agent.
18. The cured rubber composition of claim 16.
19. The cured rubber composition of claim 17.
20. A tire, tire component, a shoe sole, a hose, a seal, a cable jacket, a gasket or an industrial good containing the cured rubber composition of claim 18.
21. A tire, tire component, a shoe sole, a hose, a seal, a cable jacket, a gasket or an industrial good containing the cured rubber composition of claim 19.
22. A composition comprising:
(a) a silane-reactive filler; and
(b) at least one halo-functional silane of claim 2 andor partial hydrolyzate thereof in admixture with, or chemically bonded to, the filler of component (a).
23. The composition of claim 22, wherein the silane-reactive filler (a) is at least one selected from the group consisting of silica, titanium dioxide, aluminosilicate, alumina and siliceous materials, and combinations thereof.
24. The rubber composition of claim 16, wherein the silane (c) is pre-mixed or pre-reacted with the silane-reactive filler (b).
25. The rubber composition of claim 24 wherein the silane-reactive filler (b) is at least one selected from the group consisting of silica, titanium dioxide, aluminosilicate, alumina and siliceous materials, and combinations thereof.
26. The rubber composition of claim 17 wherein the activating agent is a transition metal salt.