Water soluble texaphyrin metal complexes for viral deactivation
First Claim
1. A method of deactivating enveloped viruses in vivo or ex vivo in an aqueous fluid, the method comprising adding a water soluble hydroxy-substituted aromatic pentadentate expanded porphyrin analog metal complex retaining lipophilicity to said aqueous fluid and exposing the mixture to light to effect the formation of singlet oxygen.
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Abstract
The present invention involves water soluble hydroxy-substituted texaphyrins retaining lipophilicity, the synthesis of such compounds and their uses. These expanded porphyrin-like macrocycles are efficient chelators of divalent and trivalent metal ions. Various metal (e.g., transition, main group, and lanthanide) complexes of the hydroxy-substituted texaphyrin derivatives of the present invention have unusual water solubility and stability. They absorb light strongly in a physiologically important region (i.e. 690-880 nm). They have enhanced relaxivity and therefore are useful in magnetic resonance imaging. They form long-lived triplet states in high yield and act as photosensitizers for the generation of singlet oxygen. Thus, they are useful for inactivation or destruction of human immunodeficiency virus (HIV-1), mononuclear or other cells infected with such virus as well as tumor cells. They are water soluble, yet they retain sufficient lipophilicity so as to have greater affinity for lipid rich areas such as atheroma and tumors. They may be used for magnetic resonance imaging followed by photodynamic tumor therapy in the treatment of atheroma and tumors. These properties, coupled with their high chemical stability and appreciable solubility in water, add to their usefulness.
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Citations
32 Claims
- 1. A method of deactivating enveloped viruses in vivo or ex vivo in an aqueous fluid, the method comprising adding a water soluble hydroxy-substituted aromatic pentadentate expanded porphyrin analog metal complex retaining lipophilicity to said aqueous fluid and exposing the mixture to light to effect the formation of singlet oxygen.
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12. A method for deactivating an enveloped virus in blood in vitro or ex vivo comprising:
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mixing with blood in vitro or ex vivo a water soluble hydroxy-substituted aromatic pentadentate expanded porphyrin analog metal complex capable of producing singlet oxygen when irradiated in the presence of oxygen; and irradiating the mixture in vitro or ex vivo to produce singlet oxygen in a quantity cytotoxic to said enveloped virus. - View Dependent Claims (13, 14, 15, 16, 17, 18, 19, 20)
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- 21. A method of deactivating enveloped viruses in vitro or ex vivo in an aqueous fluid, the method comprising adding a metal complex of 4,5-diethyl-10,23-dimethyl-9,-24-bis(3-hydroxypropyl)-16,17-(3-hydroxypropyloxy)-13,20,-25,26,27-pentaazapentacyclo[20.2.1.13,6.18,11.0.sup.14,19 ]heptacosa-1,3,5 7,9,11(27),12,14(19),15,17,20,22(25),23-tridecaene, to said aqueous fluid and exposing the mixture to light to effect the formation of singlet oxygen.
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27. A method of deactivating an enveloped virus in an aqueous fluid, the method comprising adding a water soluble hydroxy-substituted aromatic pentadentate expanded porphyrin analog metal complex retaining lipophilicity and having the structure:
- ##STR14## wherein;
M is a diamagnetic metal cation;R1 is hydroxyalkyl;
R2, R3 and R4 are alkyl; and
R5 is oxyalkyl;the molecular weight of any one of R1, R2, R3, R4 or R5 is less than or equal to about 1000 daltons; and N is an integer less than or equal to 2; to said aqueous fluid and exposing the mixture to light to effect the formation of singlet oxygen. - View Dependent Claims (28, 29, 30)
- ##STR14## wherein;
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31. A method of deactivating an enveloped virus in an aqueous fluid, the method comprising adding the Lu(III) complex of 4,5-diethyl-10,23-dimethyl-9,24-bis(3-hydroxypropyl)-16,17-bis[2-[2-(2-methoxyethoxy)ethoxy]-ethoxy]-13,20,25,26,27-pentaazapentacyclo[20.2.1.13,6.18,11.014,19 ]heptacosa-1,3,5,7,9 11(27),12,14(19),15,17,20,22(25),23-tridecaene to said aqueous fluid and exposing the mixture to light to effect the formation of singlet oxygen.
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32. A method for deactivating an enveloped virus in blood comprising:
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mixing with blood in vitro or ex vivo a Lu(III) complex of 4,5-diethyl-10,23-dimethyl-9,24-bis(3-hydroxypropyl)-16,17-bis[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]-13,20,25,26,27-pentaazapentacyclo[20.2.1.13,6.18,11.014,19 ]heptacosa-1,3,5,7,9,11(27),12,14(19),15,17,20,22(25),23-tridecaene; and irradiating the mixture in vitro or ex vivo to produce singlet oxygen in a quantity cytotoxic to said enveloped virus.
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Specification