Glycosylated Carboranylporphyrins and Uses Thereof

A method of imaging a tumor and surrounding tissue in a subject comprising:

• administering to the subject a composition comprising a compound selected from the group consisting of:
• a) a compound of the formula
• wherein:
• at least one of Y1, Y2, Y3, and Y4 represents a mono-saccharide, di-saccharide, tri-saccharide, or oligo-saccharide and at least one of Y1, Y2, Y3, and Y4 is a substituent represented by formula (2)
• —X1—(CR1R2)r-Z (2)
• wherein Z is a carborane cluster or a substituent represented by formula (3):
• wherein D is a carborane cluster;
• Y1, Y2, Y3, and Y4 are independently on either or both of the ortho and/or meta positions or on the para position on the phenyl rings;
• the Y1, Y2, Y3, and Y4 that are not a mono-saccharide, di-saccharide, tri-saccharide, or oligo-saccharide and that are not represented by formula (2) or (3) are independently hydrogen, a hydrocarbyl, non-aromatic carbocyclic, non-aromatic heterocyclic, aryl, alkylaryl, or arylalkyl group substituted with 1 to 4 hydrophilic groups selected from hydroxy, alkoxy, —C(O)OR5, —SOR6, —SO2R6, nitro, amido, ureido, carbamato, —SR7, —NR8R9, or poly-alkyleneoxide;
• X1 and X2 are independently oxygen or sulfur;
• R1, R2, R3, R4, R5, R6, R7, R8, and R9 are independently selected from hydrogen and C1 to C4 hydrocarbyl;
• r and s are independently 0 or an integer from 1 to 20;
• a, b, c, d, and e independently represent an integer from 1 to 4;
• and
• M is either two hydrogen ions, a single monovalent metal ion, two monovalent metal ions, a divalent metal ion, a trivalent metal ion, a tetravalent metal ion, a pentavalent metal ion, a hexavalent metal ion wherein the porphyrin-metal complex derived from a single monovalent metal ion is charge-balanced by a counter cation, and the porphyrin-metal complex derived from a trivalent, tetravalent, pentavalent, hexavalent metal ion is charge-balanced by an appropriate number of counter anions, dianions, or trianions;
• b) the compound of formula a) in which:
• i. a, b, c, and dare 1;
• ii. two of Y1, Y2, Y3 and Y4 are represented by formula (2);
• iii. X1 is oxygen, R1 and R2 are hydrogen, and r is 1;
• iv. Z is selected from the carborane clusters —C2HB9H10 or —C2HB10H10, wherein —C2HB9H10 is nido ortho-, meta-, or para-carborane, and —C2HB10H10 is closo ortho-, meta-, or para-carborane;
• v. the substituents represented by formula (2) are in the trans configuration;
• vii. the substituents represented by formula (2) are on the meta position of each phenyl ring;
• viii. the two Y1-Y4 not represented by formula (2) are selected from the group consisting of D or L, alpha and beta forms of glucose and galactose;
• and
• ix. M is vanadium, manganese, iron;
• ruthenium, technetium, chromium, platinum, cobalt, nickel, copper, zinc, germanium, indium, tin, yttrium, gold, barium, tungsten, gadolinium, or combination thereof;
• and
• c) the compound of formula a) in which:
• i. a, b, c, and dare 1;
• ii. two of Y1, Y2, Y3 and Y4 are represented by formula (2);
• iii. Z is represented by formula (3);
• iv. D is selected from the carborane clusters —C2HB9H10 or —C2HB10H10, wherein —C2HB9H10 is nido ortho-, meta-, or para-carborane, and —C2HB10H10 is closo ortho-, meta-, or para-carborane;
• iv. the structures —X2—(CR3R4)s-D are in the 3 and 5 positions of each phenyl ring;
• V. X1 and X2 are oxygen, R1, R2, R3 and R4 are hydrogen, r and s are 1, and e is 2;
• vi. the substituents represented by formula (2) are in the trans configuration;
• vii. the two Y1-Y4 not represented by formula (2) are selected from the group consisting of D or L, alpha and beta forms of glucose and galactose;
• and
• viii. M is vanadium, manganese, iron, ruthenium, technetium, chromium, platinum, cobalt, nickel, copper, zinc, germanium, indium, tin, yttrium, gold, barium, tungsten, gadolinium, or combination thereof;
• and the imaging said subject.

A method of bimodal cancer treatment in a subject comprising:

• administering to the subject a composition comprising a compound selected from the group consisting of:
• a) a compound of the formula
• wherein:
• at least one of Y1, Y2, Y3, and Y4 represents a mono-saccharide, di-saccharide, tri-saccharide, or oligo-saccharide and at least one of Y1, Y2, Y3, and Y4 is a substituent represented by formula (2)
• —X1—(CR1R2)r-Z (2)
• wherein Z is a carborane cluster or a substituent represented by formula (3):
• wherein D is a carborane cluster;
• Y1, Y2, Y3, and Y4 are independently on either or both of the ortho and/or meta positions or on the para position on the phenyl rings;
• the Y1, Y2, Y3, and Y4 that are not a mono-saccharide, di-saccharide, tri-saccharide, or oligo-saccharide and that are not represented by formula (2) or (3) are independently hydrogen, a hydrocarbyl, non-aromatic carbocyclic, non-aromatic heterocyclic, aryl, alkylaryl, or arylalkyl group substituted with 1 to 4 hydrophilic groups selected from hydroxy, alkoxy, —C(O)OR5, —SOR6, —SO2R6, nitro, amido, ureido, carbamato, —SR7, —NR8R9, or poly-alkyleneoxide;
• X1 and X2 are independently oxygen or sulfur;
• R1, R2, R3, R4, R5, R6, R7, R8, and R9 are independently selected from hydrogen and C1 to C4 hydrocarbyl;
• r and s are independently 0 or an integer from 1 to 20;
• a, b, c, d, and e independently represent an integer from 1 to 4;
• and
• M is either two hydrogen ions, a single monovalent metal ion, two monovalent metal ions, a divalent metal ion, a trivalent metal ion, a tetravalent metal ion, a pentavalent metal ion, a hexavalent metal ion wherein the porphyrin-metal complex derived from a single monovalent metal ion is charge-balanced by a counter cation, and the porphyrin-metal complex derived from a trivalent, tetravalent, pentavalent, hexavalent metal ion is charge-balanced by an appropriate number of counter anions, dianions, or trianions;
• b) the compound of formula a) in which:
• i. a, b, c, and d are 1;
• ii. two of Y1, Y2, Y3 and Y4 are represented by formula (2);
• iii. X1 is oxygen, R1 and R2 are hydrogen, and r is 1;
• iv. Z is selected from the carborane clusters —C2HB9H10 or —C2HB10H10, wherein —C2HB9H10 is nido ortho-, meta-, or para-carborane, and —C2HB10H10 is closo ortho-, meta-, or para-carborane;
• v. the substituents represented by formula (2) are in the trans configuration;
• vii. the substituents represented by formula (2) are on the meta position of each phenyl ring;
• viii. the two Y1-Y4 not represented by formula (2) are selected from the group consisting of D or L, alpha and beta forms of glucose and galactose;
• and
• ix. M is vanadium, manganese, iron, ruthenium, technetium, chromium, platinum, cobalt, nickel, copper, zinc, germanium, indium, tin, yttrium, gold, barium, tungsten, gadolinium, or combination thereof;
• and
• c) the compound of formula a) in which:
• i. a, b, c, and d are 1;
• ii. two of Y1, Y2, Y3 and Y4 are represented by formula (2);
• iii. Z is represented by formula (3);
• iv. D is selected from the carborane clusters —C2HB9H10 or —C2HB10H10, wherein —C2HB9H10 is nido ortho-, meta-, or para-carborane, and —C2HB10H10 is closo ortho-, meta-, or para-carborane;
• iv. the structures —X2—(CR3R4)s-D are in the 3 and 5 positions of each phenyl ring;
• v. X1 and X2 are oxygen, R1, R2, R3 and R4 are hydrogen, r and s are 1, and e is 2;
• vi. the substituents represented by formula (2) are in the trans configuration;
• vii. the two Y1-Y4 not represented by formula (2) are selected from the group consisting of D or L, alpha and beta forms of glucose and galactose;
• and
• viii. M is vanadium, manganese, iron, ruthenium, technetium, 70 chromium, platinum, cobalt, nickel, copper, zinc, germanium, indium, tin, yttrium, gold, barium, tungsten, gadolinium, or combination thereof;
• and irradiating said subject.

A compound of the formula

• wherein:
• at least one of Y1, Y2, Y3, and Y4 represents a mono-saccharide, di-saccharide, tri-saccharide, or oligo-saccharide and at least one of Y1, Y2, Y3, and Y4 is a substituent represented by formula (2)
• —X1—(CR1R2)r-Z (2)
• wherein Z is a carborane cluster or a substituent represented by formula (3):
• where D is a carborane cluster;
• Y1, Y2, Y3, and Y4 are independently on either or both of the ortho and/or meta positions or on the para position on the phenyl rings;
• the Y1, Y2, Y3, and Y4 that are not a mono-saccharide, di-saccharide, tri-saccharide, or oligo-saccharide and that are not represented by formula (2) or (3) are independently hydrogen, a hydrocarbyl, non-aromatic carbocyclic, non-aromatic heterocyclic, aryl, alkylaryl, or arylalkyl group substituted with 1 to 4 hydrophilic groups selected from hydroxy, alkoxy, —C(O)OR5, —SOR6, —SO2R6, nitro, amido, ureido, carbamato, —SR7, —NR8R9, or poly-alkyleneoxide;
• Z and D are carborane clusters comprising at least two carbon atoms and at least three boron atoms, or at least one carbon atom and at least five boron atoms, within a cage structure;
• X1 and X2 are independently oxygen or sulfur;
• R1, R2, R3, R4, R5, R6, R7, R8, and R9 are independently selected from hydrogen and C1 to C4 hydrocarbyl;
• r and s are independently 0 or an integer from 1 to 20;
• a, b, c, d, and e independently represent an integer from 1 to 4;
• and
• M is a trivalent, tetravalent, pentavalent, or hexavalent metal ion;
• and
• wherein the porphyrin-metal complex is charge-balanced by one or more porphyrin compounds containing a divalent negative charge.