Lanthanide ion complexes and imaging method

Abstract

A Ianthanide complex, method of forming and method of using the lanthanide complex as a near-infrared luminescent material are described. The complex includes at least one lanthanide ion and at least one polydentate ligand derived from a molecule having the general formula of Structure: Structure 2, where: E represents a heteroatom or heteroatom-containing group and R 1 R 8 are independently selected from H, —OH, —NH 2 , —SO 3 H, —CO 2 H, halides, optionally substituted organic groups; and conjugated linking groups which link two of the polydentate ligands of Structure 2 together.

1 . A lanthanide complex comprising at least one lanthanide ion and at least one polydentate ligand derived from a molecule having the general formula of Structure 2: 
       
         
           
           
               
               
           
         
         where:
 E represents a heteroatom or heteroatom-containing group; and 
 R 1 -R 8  are independently selected from H; —OH, —NH 2 , X, where X represents a halide; —SO 3 H; —CO 2 H; optionally substituted organic groups; and conjugated linking groups which link two of the polydentate ligands of structure 2 together. 
 
       
     
     
         2 . The complex of  claim 1 , wherein the optionally substituted organic group is selected from —OR 9 , alkyl, alkenyl, alkynyl, cycloalkyl, aryl, alkylaryl, amino, and heterocyclic groups, ring structures formed by at least two of R 1 -R 8 , and combinations thereof, and R 9  is selected from optionally substituted C 1 -C 15  groups selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, and alkylaryl groups. 
     
     
         3 . The complex of  claim 1 , wherein at least one of R 1  and R 5  is a chelating group independently selected from —CO 2 H, a dipicolyl amino group, and polyaminocarboxylic acid group, the dipicolyl amino group or polyaminocarboxylic acid group being linked through a carbon-containing bridge of from 0-2 carbon atoms. 
     
     
         4 . The complex of  claim 3 , wherein at least one of R1 and R5 is independently selected from: 
       
         
           
           
               
               
           
         
       
     
     
         5 . The complex of  claim 1 , wherein E is selected from O, S, P, Si, B, and N—R, where R represents a stabilizing group. 
     
     
         6 . The complex of  claim 5 , wherein R is selected from H and CH 3 . 
     
     
         7 . The complex of  claim 1 , wherein the lanthanide ion is selected from ions of La, Ce, Pr, Nd, Pm, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu, and combinations thereof. 
     
     
         8 . The complex of  claim 7 , wherein the lanthanide ion is selected from the group consisting of Pr 3+ , Nd 3+ , Sm 3+ , Dy 3+ , Ho 3+ , Er 3+ , Tm 3+ , Yb 3+ , and combinations thereof. 
     
     
         9 . The complex of  claim 8 , wherein the lanthanide ion comprises Yb 3+ . 
     
     
         10 . The complex of  claim 1 , further comprising at least one of a neutral ligand and an anionic ligand. 
     
     
         11 . The complex of  claim 10 , wherein the neutral ligand is present and is selected from 1,10-phenanthroline, bipyridine, triphenylphosphine oxide, dimethyl sulfoxide, bathophenanthroline, H 2 O, and combinations and optionally substituted derivatives thereof. 
     
     
         12 . The complex of  claim 10 , wherein the anionic ligand is present and is selected from the group consisting of:
 halides, acetoxy, CF 3 SO 3   − , nitride, and combinations thereof.   
     
     
         13 . The complex of  claim 1 , wherein the complex is photoluminescent. 
     
     
         14 . The complex of  claim 1 , wherein the complex has the structure of Structure 3: 
       
         
           
           
               
               
           
         
         where Ln represents the lanthanide ion and p is from 1 to 4. 
       
     
     
         15 . The complex of  claim 1 , wherein the lanthanide complex comprises two of the polydentate ligands which are linked by a linking group. 
     
     
         16 . The complex of  claim 15 , wherein the polydentate ligand has the general structure of Structure 14: 
       
         
           
           
               
               
           
         
         where E′ represents a heteroatom or heteroatom-containing group; 
         R 14  and R 15  represent a substituent independently selected from R 1 , R 2 , and R 4 ; and 
         R 16  represents a conjugated linking group. 
       
     
     
         17 . The complex of  claim 16 , wherein the conjugated linking group is selected from Structures 15 and 16: 
       
         
           
           
               
               
           
         
       
     
     
         18 . The complex of  claim 1 , wherein the polydentate ligand is selected from Structures 5-13 and 17-19: 
       
         
           
           
               
               
           
         
       
       where R 3 ═H, X, alkoxy, amino, or CH 3 , and
 R 5 ═H, —COOH, amino, or polyamino; 
 
       
         
           
           
               
               
           
         
       
       where R 12 ═R 6  and R 5 ═H, —COOH, amino, or polyamino; 
       
         
           
           
               
               
           
         
       
       where R represents a stabilizing group; 
       
         
           
           
               
               
           
         
       
       where R 13  represents a stabilizing group and is optionally the same as R, 
       
         
           
           
               
               
           
         
       
     
     
         19 . The complex of  claim 18 , wherein the complex is selected from Structure 5 and Structure 7 and wherein R 5  is selected from 
       
         
           
           
               
               
           
         
       
     
     
         20 . The complex of  claim 1 , wherein the complex has the general form of one of the group consisting of Ln 2 L 1   6 , LnL 1   3 L 2 , MLnL 1   4 , LnL 1   3 .DMSO, LnL 1 A 2 , and LnL 1   2 A, where Ln represents the lanthanide ion, L 1  represents the polydentate ligand, L 2  represents a neutral ligand, X represents an anion, such as a halide, and M represents a cation. 
     
     
         21 . A solution comprising the complex of  claim 1 . 
     
     
         22 . A solid comprising the complex of  claim 1 . 
     
     
         23 . A photoluminescent probe comprising the complex of  claim 1  and at least one of a biomolecule and a biocompatible synthetic polymer coupled to the complex. 
     
     
         24 . The probe of  claim 23 , wherein the biomolecule is selected from hormones, amino acids, peptides, peptidomimetics, proteins, nucleosides, nucleotides, nucleic acids, carbohydrates, lipids, albumins, mono- and polyclonal antibodies, receptor molecules, receptor binding molecules, aptamers, and combinations thereof 
     
     
         25 . A pharmaceutically acceptable composition comprising the complex of  claim 1 . 
     
     
         26 . The pharmaceutically acceptable composition of  claim 25 , wherein the complex is present at a concentration of at least 1 nanomoles/liter. 
     
     
         27 . The pharmaceutically acceptable composition of  claim 25 , further comprising an anticancer drug. 
     
     
         28 . A compound comprising the complex of  claim 1 , wherein the compound has the structure of Structure 1:
   M m   + [(Ln) n L 1   p A q L 2   z ]  Structure 1,
   where L 1  represents the polydentate ligand;   M +  represents an optional monovalent cation;   Ln represents the lanthanide ion;   A represents an optional anion;   L 2  represents an optional neutral ligand; and   m, q, and z are at least 0, and n and p are each at least 1.   
     
     
         29 . The compound of  claim 28 , wherein m is 1 or 2. 
     
     
         30 . The compound of  claim 28 , wherein n is 1 or 2. 
     
     
         31 . The compound of  claim 28 , wherein p is from 1-6. 
     
     
         32 . The compound of  claim 28 , wherein the compound includes at least one neutral ligand L 2  selected from 1,10-phenanthroline, bipyridine, triphenylphosphine oxide, dimethyl sulfoxide, bathophenanthroline, H 2 O, and combinations and optionally substituted derivatives thereof. 
     
     
         33 . The compound of  claim 28 , wherein the compound includes at least one anionic ligand, which is selected from halides, acetate, CF 3 SO 3   − , nitride, and combinations thereof. 
     
     
         34 . The compound of  claim 28 , wherein the cation is present and is selected from ammonium and lithium cations and combinations thereof. 
     
     
         35 . A method of forming a lanthanide complex comprising combining a lanthanide ion with a ligand-forming molecule having the general formula of Structure 2: 
       
         
           
           
               
               
           
         
         where:
 E represents a heteroatom or heteroatom-containing group; and 
 R 1 -R 8  are independently selected from H; —OH; —SO 3 H; —CO 2 H; —NH 2 ; X, and optionally substituted organic groups and where X represents a halide. 
 
       
     
     
         36 . The method of  claim 35 , wherein the combining includes combining the lanthanide ion with the ligand-forming molecule in a solvent. 
     
     
         37 . The method of  claim 35 , wherein the solvent is selected from C 1 -C 6  alcohols, dimethyl sulfoxide, and combinations thereof. 
     
     
         38 . The method of  claim 35 , wherein the combining further comprises combining the ligand forming molecule with a compound which forms a linking group between two of the polydentate ligands. 
     
     
         39 . The method of  claim 35 , wherein the lanthanide ion is in the form of a salt. 
     
     
         40 . The method of  claim 35 , wherein the combining includes combining the lanthanide ion with the ligand-forming molecule in the presence of a tertiary amine in solution. 
     
     
         41 . The method of  claim 35 , wherein the combining further comprises combining the lanthanide ion with the ligand-forming molecule and a base comprising a cation which forms a compound with the lanthanide ion complex. 
     
     
         42 . The method of  claim 35 , wherein the combining further comprises combining the lanthanide ion with the ligand-forming molecule and a neutral ligand forming molecule. 
     
     
         43 . The method of  claim 35 , wherein the combining is performed in the presence of a base comprising a cation which does not complex with the lanthanide ion. 
     
     
         44 . The method of  claim 35 , wherein the complex forms as a precipitate from solution. 
     
     
         45 . The method of  claim 35 , wherein the complex forms a homogeneous solution. 
     
     
         46 . A method of detecting a concentration of a drug at a disease site comprising coupling the complex of  claim 1  with a drug, administering the coupled complex and drug to a patient, and detecting the concentration of the drug at the disease site as a function of photoluminescence by the complex. 
     
     
         47 . The method of  claim 46 , further comprising irradiating the patient with light in a wavelength range which is absorbed by the complex. 
     
     
         48 . The method of  claim 46 , wherein the detecting includes detecting emitted radiation in a selected Near Infra Red (NIR) range at which the photoluminescence occurs.