Porphyrins derivatives with boron

FIGURE 10.10 Boronated porphyrin derivatives with carbon-carbon linkages. 

The use of nanocontainers, such as low-density lipoproteins (LDL) or liposomes is the important approach directed to selective delivery of therapeutics into tumors. One of the observed differences between tumor cells and their normal counterparts is the rate of metabolism of low-density lipoproteins (LDLs). The LDL vesicle comprises a phospholipids/cholesterol shell with a diameter of approximately 15-20 nm, filled with cholesteryl and glyceryl esters of long-chain alkyl carboxylic acids. This difference is based on the increased need that tumor cells possess for cholesterol to facilitate new membrane formation. The overexpression of the LDL receptors on the tumor cell membrane is responsible for its LDL accretion. This provides a basis for cellular differentiation and the targeting of tumor cells with boron if cholesteryl esters of the LDL core are replaced with a boron species that would simulate cholesterol in its physiochanical properties. This concept was proposed by Kahl in the early 1990s. The initial compounds synthesized were esters of carborane carboxylic acid with various fatty acid alcohols [80]. Later, some other derivatives of cholesterol were synthesized [81,82] and LDLs were proposed as tumor delivery agents for carborane-containing porphyrins [83]. 

The second strategy of the synthesis of boronated biomolecules using cyclic oxonium derivatives of polyhedral boron hydrides is based on direct reaction of their cyclic oxonium derivatives with nucleophilic sites of premodified biomolecules or their analogs. This approach was successfully used for the preparation of boronated porphyrins and nucleosides. 

To date, the most extensively studied polyboron hydride compounds in BNCT research have been the icosahedral mercaptoborane derivatives Na2[B22H22SH] and Na [(B22H22S)2], which have been used in human trials with some, albeit limited, success. New generations of tumor-localizing boronated compounds are being developed. The dose-selectivity problem of BNCT has been approached using boron hydride compounds in combination with a variety of deUvery vehicles including boronated polyclonal and monoclonal antibodies, porphyrins, amino acids, nucleotides, carbohydrates, and hposomes. Boron neutron capture therapy has been the subject of recent reviews (254). 

The reaction of the porphyrin ligand, TTP (tetra-p-tolylporphyrin) with BF3-OEt2 leads to the oxide fluoride complex, B2OF2(TTP) and the structure has been established using H, 13C, nB and 19F NMR spectroscopy and FAB mass spectrometry [9], The structure contains a B—O—B bridge in which each boron is bonded to fluorine and to a nitrogen of TTP. The structure of the diboron complex was confirmed by an X-ray crystal structure determination of the tetrakis-(p-chlorophenyl)porphyrin (TpCiPP) derivative. 

Since the initial disclosure of the above synthesis of inverted porphyrins 3.160 and 3.161, two rational synthetic approaches to structures of this type have been devised. The first of these, reported by Lee and coworkers, actually involved the synthesis of the furan-containing system 3.167 (Scheme 3.5.3). In this approach, diol 3.165 was condensed with the tripyrrane derivative 3.166 using boron trifluoride etherate as the acid catalyst. After oxidation with DDQ, the inverted monoxapor-phyrin 3.167 was isolated in 5.5% yield. 

As we will see, the choice of electron donors associated with porphyrins has not evolved much over the years. In previous review articles, electron donors such as carotenes, aryl amines, and ferrocene derivatives have been examined. Concerning the class of energy donors, over the past decade, boron dipyrylmethanes (BODIPY) are probably the most widely used series of compounds. A very detailed study of their association and their excitation energy transfer to porphyrins has been carried out by LindseyIt should be noted that condensed aromatics such as anthracene, and especially perylene derivatives, may be good substitutes for BODIPYs. 

Other carboranylporphyrins and boronated chlorine eg for PDT, in which porphyrin is linked to the carboranyl moiety via the boron or the carbon atoms have also been reported by OTshevskaya et al. In arecent work, boronated amide derivatives starting from 5,10,15,20-tetra(p-aminophenyl) porphyrin and 9-o- and 9-m-carborane carboxylic acid chlorides were prepared. Also, the reaction of 2-formyl-5,10,15,20-tetraphenylporphyrin with the lithium salt of 1,2-c/oso-C2BjoHj2, and... 

Figure 8 View of a Zn(II)-based MOF that combines a tetracarboxylate-derived porphyrin with a bis-pyridyl substituted BODIPY (difluoro-boron-dipyrromethene) ligand. (Reprinted with permission from Ref 41. Copyright (2011) American Chemical Society.)...

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