Modern Aspects of Main Group Chemistry - ACS Publications

Chapter 22

Polyhedral Boranes in the Nanoworld

Downloaded by UNIV OF AUCKLAND on May 3, 2015 | http://pubs.acs.org Publication Date: December 1, 2005 | doi: 10.1021/bk-2005-0917.ch022

M . Frederick Hawthorne, Omar K . Farha, Richard Julius, Ling Ma, Satish S. Jalisatgi, Tiejun Li, and Michael J. Bayer Department of Chemistry and Biochemistry, University of California at Los Angeles, Los Angeles, CA 90095

Aromatic polyhedral boranes and carboranes lend themselves to the construction of nanoesque structures suited for unique applications. These include cyclic, water-soluble hosts having a lipophilic core; self-assembling nanorods and bilayer membranes using amphiphilic carborane derivatives; and the huge family of functional structures obtainable from the [closo-B (OH) ] by derivatization of the hydroxyl groups. The latter species are potentially useful for molecular delivery devices important to biomedicine and material science. New developments in each of these areas of interest will be presented. 2-

12

12

1,2

As previously pointed out, of all the elements of the periodic table, only neighboring carbon and boron share the properties of wide-spread self-bonding (catenation) and the support of electron-delocalized structures based upon these catenated frameworks. Carbon catenation, of course, leads to the immense field of organic chemistry. Boron catenation provides the nido-, arachno-, and hyphoboranes, which may be considered the borane equivalents of aliphatic hydrocarbons, and discrete families of c/oso-borane derivatives which bear a formal resemblance to aromatic hydrocarbons, heterocycles and metallocenes. Asidefromthese analogs, boron and carbon chemistries are important to each other through their extravagant ability to mix in ways not available to other

312

© 2006 American Chemical Society In Modern Aspects of Main Group Chemistry; Lattman, M., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2005.

313

element pairs. This history of merging chemistries continues to offer new opportunities now and into the foreseeable future. Recently, nanotechnology has received a great amount of attention due to the promise of its potential applications. Much of this attention has been focused upon carbon-based nanoparticles: nanotubes, nanoscrolls and most famously, buckminsterfullerene. Integral to the success of these structures is carbon's aforementioned catenation ability. In this chapter, we demonstrate how boron's ability to catenate and mix with carbon in the form of polyhedral borane derivatives and carboranes allows the creation of novel nanoparticles, as well.


3

Commercially Available Boranes, Carboranes and Metallacarboranes Boronhydride chemistry underwent a tremendous expansion in the 1950's. Extraordinarily stable [closo-BnHn] ' (1) and [c/aso-BioHio] ' (2) anions were discovered over 40 years ago. Continued expansion in the field occurred with the synthesis of c/o-so-carborane derivatives, [c/oso-CBnHn]" (3) ; the three isomeric dicarbon carboranes, c/oso-l,2-C Bi Ht (4),c/aso-l,7-C BioHi (5) and closo-l,12-C BioHi (6), commonly known as ortho,meta, and paracarboranes. The derivative chemistry of all of these molecules has been wellestablished, with much new chemistry continuing to be discovered at an everexpanding rate. 2

2

4,5

2

2

0

2

2

2

2

6

7,8

9,10

The icosahedral metallacarboranes are very stable metal complexes in which the metal may be considered to be coordinated to the open QB3 pentagonal face of a dicarbollide ion («iV/o-C B Hn ), which is analogous to a cyclopentadienyl anion. Due to a number of factors, metallacarboranes are even more stable than their cyclopentadienyl analogs. A wide variety of structures are available, in which both the metal and associated ligands may be varied in numerous ways, as shown in the representative structures 7,8 and 9. 2

2

9

11

12

l

n

n

-

• = CH 0 = BH

In Modern Aspects of Main Group Chemistry; Lattman, M., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2005.

314 Permethylation of Icosahedral Borane Derivatives Substitution of the vertices of icosahedral borane derivatives provides a route to the confluence of polyhedral borane and hydrocarbon chemistries, combining the unique chemical properties of the boranes, such as their extreme kinetic stability and three-dimensional aromaticity, with the synthetic arsenal of organic chemistry. Methylation of all vertices of the icosahedral structure leads to the permethylated species, of which the dodecamethyl-l,12-dicarba-c/a5ododecaborate, c/as0-l,12-C2Bi (CH )i2, (10) dodecamethyl-l-carba-c/asododecaborate(l-), [c/0S0-CBu(CH )i ]" (U) and dodecamethyl-c/osododecaborate (2-), [c/0sc^Bi (CH )i2] "(12) species are all known. 13

14

O

3

15

3

2

2


2

13

3

10

11

•ο == BHc

1. CH I/AICI 3

•

3

2. AI(CH )

3 3

= BCH

3

12 The resulting permethylated species have increased hydrophobicity and van der Waals diameters. These properties are analogous to those of buckminsterfullerene, as shown below, while maintaining the great chemical versatility found in borane chemistry.

•ο = c •

990 p m

=Β = BCH

1070 p m


3

315 Perhydroxylation of Icosahedral Borane Derivatives Icosahedral boranes and carboranes may also be hydroxylated to produce [c/o5o-Bi (OH),2] " (13) , [c/ojo-CHBi,(OH)n]" (14) and closo-l,\2C2H Bio(OH), (15) resulting in a hydrophilic species having easily derivatized BOH vertices and aromatic properties. 2

16

2

7


2

0

2

Further functionaliztion of [c/oso-Bi (OH)i ] " was completed to obtain three different linker motifs, the ester , ether and carbamate, as shown below. Such derivatives are known as "closomers". 2

18

2

1

20

ROCI/R3N

1.2[BOOR]

2

[BtttOHM -

7

22

RCH Br/ R N

,

RNCO

^ __!L

2

3

1 2

r

,2-

[BOCNHR]ÎJ


316 Current Applications of Boranes and Carboranes in Supramolecular Chemistry and Nanoscience

Stable Unilamellar Liposomes for Boron Neutron Capture Therapy Liposomes, spherical phospholipid bilayer structures, have attracted a great deal of interest as drug delivery vehicles for cancer therapy, including Boron Neutron Capture Therapy (BNCT). Preferential uptake by cancer cells as well as reduced drug toxicity due to drug isolation support this interest. Compounds 16 and 17 have both been incorporated into phospholipids bilayers and used to encapsulate Naall-^'-BioHc^-NHsBioHe] in the aqueous inner core of liposomes with high boron content, a necessity for effective BNCT. Species 17 has been synthesized. This compound has the advantage of not requiring the addition of distearoylphosphocholine to form the liposome bilayer, resulting in a higher overall boron content. 21


22

Na-HT

CHg-O-n-C^Haj Na l^-^CH -0-CH ^ ^ CH -0-/>C H 3 +

^n-C H ie

2

33

16

(

k

s

mû

r

2

16

3

17

Liposomes containing 16:cholesterol:distearoylphosphocholine in a 1:3:3 molar ratio form 100 nm diameter liposomes which contain 2.5 wt % boron, while liposomes using 17:cholesterol in a 1:1 molar ratio produce 40 nm liposomes with an increased 8.8 wt. % boron content. This significantly amplifies the efficiency of boron delivery to tumor cells.

SelfAssembly ofRod Structures It has been found that linear and amphiphilic derivatives of Q , which have a distinct hydrophobicity and hydrophilicity balance, could self-assemble into rod-like structures. Recognizing the importance of the fact that the size, shape and hydrophobicity of permethylated carboranes resemble that of Ceo and thus they may be regarded as surrogates, it was thought that an analogous permethylated carborane assembly could be formed. Employing the following scheme, rods were formed containing the proposed repeating structure shown below. 0

23

24


317

(CH2) NH CÎ 3

3

H 0 Sonicate


2

The stability of the proposed repeating structure is based upon NH—CI hydrogen bonding as well as hydrophobic interactions between the permethylated carborane cages. As shown by TEM, the rods were approx. 300 nm in diameter and greater than 70 micrometers in length.

Carboracycles:Hydrophilic Support of Encapsulated Hydrophobic Species Interest in the development of new supramolecular chemistry and its use in molecular recognition in solvent systems that range from organic to aqueous led to the development to new water-soluble carborane-containing structures. The hydrophilic outer layer encapsulates a hydrophobic interior capable of solvating a hydrophobic guest. 25



318

Closomers: A New Motif in Molecular Architecture Extensive substitution of a c/oso-polyhedral borane or carborane surface by precisely constructed polyatomic moieties forms closomers. Closomers may have several types of substituents, such as branched (dendritic) or linear (oligomeric) chains with or without functional chain substituents. 18,19

Dendritic Closomer

Oligomeric Closomer


319 Closomeric structures provide camouflaged, multifunctional modules of variable size, shape, charge, hydrophobicity and other properties designed to accomplish specific functions important to such fields as biomedicine and material science.

Jahn-Teller Distortion Accompanying the Two-Electron Oxidation of [ClosoB (OCH Ph) ] ' 2

l2

2

i2

Ether-linked closomers are unique in their susceptibility to oxidation, as shown below. The oxidation of the ether closomers have been shown to cause a Downloaded by UNIV OF AUCKLAND on May 3, 2015 | http://pubs.acs.org Publication Date: December 1, 2005 | doi: 10.1021/bk-2005-0917.ch022

Jahn-Teller distortion and a change in the point group of the molecule from Ih to D .

1 9

3 d

2

(c/oso-B^OCI^Ph)^] ""

e

e~ ~» θ

l 26 e -

"~

h

[hyperctoso-B 2(OCH Ph) 2] · 1

2

Approx. l

1

25 e-

h

~

e

[hyperc/oso-B (OCH2Ph) ] 12

Approx. l

h

»

12

25 e ~

[hypercloso-B^OC^Ph)^ D

3d

24 e~

An additional feature of ether-linked closomers is the tunability of their redox potentials made possible by changing their cage substituents. 26

Closomers in Drug Delivery The ability to conjugate up to twelve copies of pharmaceutical ligands to the icosahedral dodecaborate (2-) cage makes closomers attractive drug delivery vehicles which can result in an increase of drug released at the therapeutic site. Ampicillin, an inexpensive prototype pharmaceutical, has been used in proof of principle studies. 27


320

Closomers ofHigh Boron Contentfor Use in Boron Neutron Capture Ther Derivatives of the icosahedral dodecaborate (2-) core surrounded by twelve pendant carborane groups have been synthesized using ester and ether linkages. When the associated pendant carborane groups are degraded to the corresponding anionic nido species, water solubility greatly increases. The resulting boron-rich and water-soluble molecules are very attractive BNCT target candidates.


28,24

Vertex Differentiation for the Targeting ofSpecific Sites The enhancement of the number of contrast agents per cell is desirable for greater image resolution in MRI. One way to achieve this is through directed substitution of cell-targeting ligands on the icosahedral dodecaborate cage. This allows the precise control of size, shape and placement of functional groups, which is desirable for many life science applications. The reaction scheme shown below will generate a unique molecule that contains two different functional motifs in the ratio of 1:10. This could lead to specific cell targeting of large payloads for MRI, drug delivery, radioimaging, chemotherapy of cancer and many other applications. 29

30

Water-soluble Carborane Scaffoldfor Closomer Chemistry The exploratory study of c/oso-B-perhydroxylated-p-carborane shown below demonstrates that its C-H vertices can be utilized as platforms for substituents which control its solubility and reactivity. By placing sulfonate groups at the 1- and 12- positions of water-insoluble 18, the methanol-soluble species 19 was formed and successfully converted to its water-soluble


321

2ΌΡ(ΟΡη)

1 2


OH" " ? CIP(OPh)

+

Pyridine

2

,

2

Heat

2

2

ο

2-

"Ί

30% H 0

Π

II OP(OH)

2

(Aco) -gOl

Ac,0

A

10

OH (OH)„ Br(CH ) COOCH 2

4

3

• =B 0=BH

I' 2

γ ς/

etc. 0(CH2) COOCH 4

3


2

"

322


• = C 0=BH #=BOCH

3

J>

perhydroxylated derivative 20. The resulting species presents the advantages of facile derivitization of the BOH vertices and two distinguishable reactive sites in a hypothetical extended closomer structure.

A Rotary Molecular Motor Based on a Unique Nickelacarborane The basis for the molecular device shown here has been known since the early 1970s. The following diagram shows the d Ni(III) and d Ni(IV) commobis-7,8-dicarbollyl metallacarboranes. The interconversion between these two geometries occurs when the oxidation state of nickel is changed and provides the basis for controlling the movements of this nanodevice. 7

6

32,33

(Reproduced with permission from Reference 33. Copyright 2004 Ame Association for the Advancement for the Advancement of Science)


323

This rotation could allow for the control of nanovalves and switches, reversible exposure of catalytic sites and other applications where selective surface exposure is necessary.

References:


1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21.

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th

22. Li, T., Thomas, J., Hawthorne, M . F., Abstracts of Papers, 225 National Meeting of the American Chemical Society, New Orleans, LA, March 2327, 2003; American Chemical Society: Washington, DC 23. Cassell, A. M., Asplund, C. L., Tour, J. M . Angew. Chem. Int. Ed. 1999, 38, 2403-2405. 24. Ma, L., Hawthorne, M . F. 2004 Unpublished Results 25. Bayer, M . J., Herzog, Α., Diaz, M., Harakas, G. Α., Lee, H., Knobler, C. B., Hawthorne, M . F. Chem. Eur. J. 2003, 9, 2732-2744. 26. Farha, Ο. K., Hawthorne, M . F. 2004, Unpublished Results 27. Jalisatgi, S. S., Hawthorne, M . F. 2004, Unpublished Results 28. Thomas, J., Hawthorne, M . F. Chem. Commun. 2001, 1884-1885. 29. Artemov, D. J. Cell. Mol. Med. 2003, 90, 518-524. 30. Bayer, M . J., Hawthorne, M . F. 2004, Unpublished Results 31. Herzog, Α., Knobler, C. B., Hawthorne, M . F.J. Am. Chem. Soc. 2001, 123, 12791-12797. 32. Warren, Jr., L. F., Hawthorne, M . F. J. Am. Chem. Soc. 1970, 92. 11571173. 33. Hawthorne, M . F., Zink, J. I., Skelton, J. M., Bayer, M . J., Liu, C., Livshits, E., Baer, R., Neuhauser, D. Science, 2004, 1849-1851.


Modern Aspects of Main Group Chemistry - ACS Publications

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