Covalent modification of metal surfaces

Abstract

The present invention provides modified metal surfaces, methods of preparing the same, and intermediates thereto. These materials are useful in a variety of applications including biomaterials.

1 .- 15 . (canceled) 
     
     
         16 . A compound of formula II-e: 
       
         
           
           
               
               
           
         
         or a salt thereof, wherein: 
         W is —C(═O)OH, —C(═O)X, —P(═O)(OH) 2 , —P(═O)(X) 2 , —P(═O)(R a )OH, —P(═O)(R a )X, —Si(R a ) 2 OH, —Si(OR a ) 2 OH, —Si(R a ) 2 X, —Si(R a )(OH) 2 , —Si(R a )X 2 , —Si(OR a ) 2 X, or N═C═O; 
         each X is independently Cl, Br, or I; and 
         each R a  is hydrogen, an alkyl group, or an aryl group; 
         y is 1-2500; 
         each R is independently hydrogen or an optionally substituted aliphatic group; 
         L 1  is a valence bond or a bivalent, saturated or unsaturated, straight or branched C 1-12  alkylene chain, wherein 0-6 methylene units of L 1  are independently replaced by -Cy-, —O—, —NR—, —S—, —OC(O)—, —C(O)O—, —C(O)—, —SO—, —SO 2 —, —NRSO 2 —, —SO 2 NR—, —NRC(O)—, —C(O)NR—, —OC(O)NR—, or —NRC(O)O—, wherein:
 each -Cy- is independently an optionally substituted 3-8 membered bivalent, saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an optionally substituted 8-10 membered bivalent saturated, partially unsaturated, or aryl bicyclic ring having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; and 
 
         L 2  is a valence bond or a bivalent, saturated or unsaturated, straight or branched C 1-12  alkylene chain, wherein 0-6 methylene units of L 2  are independently replaced by -Cy-, —O—, —NR—, —S—, or —C(O)—, wherein:
 each -Cy- is independently an optionally substituted 3-8 membered bivalent, saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an optionally substituted 8-10 membered bivalent saturated, partially unsaturated, or aryl bicyclic ring having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur. 
 
       
     
     
         17 . An implantable device, wherein at least a portion of said device is a covalently modified metal surface. 
     
     
         18 . The implantable device according to  claim 17 , wherein said device is PEGylated. 
     
     
         19 . The implantable device according to  claim 17 , wherein said device is selected from cardiovascular devices (e.g., implantable venous catheters, venous ports, tunneled venous catheters, chronic infusion lines or ports, including hepatic artery infusion catheters, pacemaker wires, implantable defibrillators); neurologic/neurosurgical devices (e.g., ventricular peritoneal shunts, ventricular atrial shunts, nerve stimulator devices, dural patches and implants to prevent epidural fibrosis post-laminectomy, devices for continuous subarachnoid infusions); gastrointestinal devices (e.g., chronic indwelling catheters, feeding tubes, portosystemic shunts, shunts for ascites, peritoneal implants for drug delivery, peritoneal dialysis catheters, implantable meshes for hernias, suspensions or solid implants to prevent surgical adhesions, including meshes); genitourinary devices (e.g., uterine implants, including intrauterine devices (IUDs) and devices to prevent endometrial hyperplasia, fallopian tubal implants, including reversible sterilization devices, fallopian tubal stents, artificial sphincters and periurethral implants for incontinence, ureteric stents, chronic indwelling catheters, bladder augmentations, or wraps or splints for vasovasostomy); otolaryngology devices (e.g., ossicular implants, Eustachian tube splints or stents for glue ear or chronic otitis as an alternative to transtempanic drains); and orthopedic implants (e.g., cemented orthopedic prostheses). 
     
     
         20 . The implantable device according to  claim 19 , wherein said device is a stent. 
     
     
         21 . A method for expanding the lumen of a body passageway, comprising inserting a stent into the passageway, the stent having a generally tubular structure, at least a portion of the surface of the structure being covalently modified according to the method of claim  1 , such that the passageway is expanded.