Degree Type

Dissertation

Date of Award

2014

Degree Name

Doctor of Philosophy

Department

Chemistry

First Advisor

Thomas A. Holme

Abstract

Boron, a fairly simple atom in the first row of periodic table, makes remarkable dative bonds, which have inspired the curiosity of researchers for decades. Boron has three valence electrons and when in compounds the boron atom is often sp2 hybridized and has a planar structure. An empty p-orbital, which has the capability of accepting an electron pair, makes boron a good Lewis acid and once the lone pair is gained the structure around the boron becomes tetrahedral. While Boron-Nitrogen, B-N dative bonds have been extensively studied throughout the years, other boron dative bonds such as B-O and B-P also have shown remarkable characteristics.

Boron-Nitrogen containing compounds such as ammonia borane, metal amidoboranes, and organoboron boron compounds have shown to be promising hydrogen storage materials. These compounds release hydrogen upon heating, which, can be used as a clean energy source. Thermolysis of amino-boron compounds is an exothermic process. Once the initial hydrogen is released it will gives out enough energy for a self-sustained hydrogen release. But this ongoing exothermic reactions increase the temperature of the system and can even cause breaking of boron-nitrogen bond, forming low molecular weight byproducts such as borone, ammonia and borozine, that can pollute the proton exchange membrane fuel cells (PEM fuel cells). This type of technological utility adds to the interest in carrying out studies to understand the B-N bond energies of different boron nitrogen compounds. Knowing the dissociation bond energies for B-N is useful in controlling the reaction temperatures of thermolysis process.

Boron neutron capture therapy (BNCT) is a powerful form of radiotherapy, which incorporate 10B-containing compounds into tumor cells, followed by the irradiation of tumor/cancer cells with thermal neutrons. Subsequent to absorbing the neutron, the resulting 11B is unstable and decays into Li and 4He, a high-energy reaction, which destroys tumor cells without damaging as many of the surrounding healthy cells as other forms of chemotherapy. The most important requirement for the boron neutron-capture therapy is the high and selective accumulation of boron in tumor cells, where the boron-containing molecule should adhere to both boron and to the targeted cancer cell. Finding boron compounds with high selectivity, water solubility and low toxicity in high concentrations is a major problem in the advancement of treatment using BNCT. Therefore studying of boron binding environments is essential in the field of radiotherapy. Phosphorous, which plays an important role in human body as phosphates is a good example of selective boron binding for treatment of cancer cells. In addition to its part as an essential building block in DNA and RNA and as an energy transporter in the form of nucleoside di- and triphosphate, it contributes strongly to the strength and integrity of the bone skeleton.

Bisphosphonates, used as a treatment for diseases like osteoporosis and rheumatoid arthritis, can be strongly adsorbed to hydroxylapatite crystals. Hydroxylapatite crystals are substances that are found in increased quantities in bone cancer cells. Phosphorous makes dative bonds with boron. With an extended study of the strength of the boron-phosphorous bond strength; bisphosphonates might be used as a boron carrier for boron neutron capture therapy. In addition to phosphorous it has been found that both oxygen and nitrogen containing molecules also acts as selective boron carriers for BNCT.

The pharmacological uses of boron compounds have also been known for decades. In animal cells at pH values that are present, almost all-natural boron exists as boric acid, which forms molecular additive compounds with many biological compounds such as, amino and hydroxy acids, nucleotides and carbohydrates through the formation of electron donor-acceptor interactions. Recent findings of boron analogous of amino acids and their derivatives express anti-inflammatory, antineoplastic, and hypolipidemic properties. Most available dietary boron supplements use boron chelated with amino acids or hydroxy acids (citric acid, aspartic acid or glycine) in combination with vitamins. However the molecular structure of these boron chelates is poorly understood. It is essential to understand the dative bond strength of a number of boron containing bonds, including B-N, since this bond strength can govern the possible structures for drug design for various diseases to aide in understanding its function in affected sites.

Boric acids and borate anions can be combined with organic compounds to form molecules that contain B-O-C bonds (alcohols and carboxylic acids) so they are capable of forming organic esters.

H3BO3 + 3R(OH) --> B(OR)3 + 3H2O

As shown in the equation above, boric acid reacts with an primary alcohol R(OH) in a reversible reaction gives out borate di-ester and water molecules. Both boric and boronic acids can form either neutral or anionic esters depending on the pH of the system. Diol binding by boron acids is favored at high pH values, whereas the esterification of boron by hydroxycarboxylic acids is favored at low pH ranges. At high pH values boron acids can also form an anionic, tetrahedral diester with a couple of diols or with a diol and a relevant divalent ligand. The reversible reaction of esterification of boronic acids has been used in the health industry for developing blood sugar monitoring techniques for diabetics and the same reaction with boric acid is used in the study of plant cell wall biosynthesis where the borate diol cross-linked to connect two side chains of Rhamnogalacturonan II (RG-II) macromolecule which controls the growth of the plant cell wall.

Boron-based glucose receptors for incorporation as sensors in blood sugar monitors for diabetics have developed during the past two decades. The relative affinity of boronates for diols in most carbohydrates follows the order of cis-1,2-diol > cis-1,3- diol >> trans-1,2 diol. Therefore it is clear that certain monosaccharides have an intrinsically higher affinity for boron acids. It has been found that the boron-binding site for a monosaccharide depends on both the type of boron acid and the type of monosaccharide. For an example, boronates has the ability to bind to the 1,2-diol and trans-4,6- diol of glucose in its hexopyranoside form, boronic acid has an affinity for the furanoside form of free hexoes18 and galactopyranoside has an affinity for cis-3,4-diol and trans-4,6-diol.

Rhamnogalacturonan II (RG-II) is a structurally complex pectic polysaccharide, which is conserved in the plant cell wall despite the evolutionary variation of plants. RG-II contains homogalacturonan backbone composed of at least eight 1-->4 linked alpha-d-galacturonic acid residues. Four different complex oligo glycosyl side-chains named side chain A, side chain B, side chain C and side chain D that contain twelve different glycosyl residues are attached to this backbone. RG-II may exist as a dimmer, which contributes to the strength of the plant cell wall. Covalently cross-linking two side chains by a borate diester lead to RG-II dimerization. The boron needed for the borate binding is absorbed by the plant from the soil solution in the form of either boric or borate acids. The boro-diester reaction occurs in between two alpha-d-apoise (3-C-hydroxymethyl-D-erythrose) monomers in the side chain A of RG-II structure. The borate esterification is believed to be happened in cis-2,3 diol position. Structure of RG-II and its functions has been studied for more than four decades; still the structure and the functions of RG-II are not completely understood. Therefore the study of borate cross-linking carbohydrates can give some insights in to this complex macromolecule.

Boron is acts as a Lewis acid abduct over a range of fields. The comparable size of boron atom to carbon atom and the strength of dative bonds and the ability to undergo reversible reactions makes a boron a good candidate for the fields of energy, biology, medicine and plant cell biology. As a whole, study of boron binding environments can give insights for many unanswered questions.

DOI

https://doi.org/10.31274/etd-180810-3698

Copyright Owner

Chamila Chandima De Silva

Language

en

File Format

application/pdf

File Size

187 pages

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