Todd Houston - Academia.edu (original) (raw)

Papers by Todd Houston

Research paper thumbnail of Design and Synthesis of Boronolectin Fluorescence Sensors

This thesis reports on the use of the element boron in organic chemistry. Its role in catalysis, ... more This thesis reports on the use of the element boron in organic chemistry. Its role in catalysis, as well as its broad utility when in the form of a boronic acid functional group is demonstrated. Boric acid and boronic acids have applications in numerous kinds of chemical reactions as catalysts. Boric acid is demonstrated in this work to catalyse the esterification of a- hydroxycarboxylic acid starting materials, including carbohydrates, typically in excellent yield. A series of reactions were conducted to demonstrate the utility and limitations of this technique. Included in this work is the synthesis of the carbohydrate, KDO. Furthermore, a series of esters were generated using salicylic acid as a starting material, one of which was subjected to x-ray crystallographic studies. Also in this thesis a novel type of boronic acid catalysed amide forming reaction is described. The reaction is shown to proceed rapidly under mild reaction conditions with little purification required to giv...

Research paper thumbnail of Carbohydrate-based nanocarriers and their application to target macrophages and deliver antimicrobial agents

Advanced Drug Delivery Reviews, 2019

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Research paper thumbnail of Thioamide Derivative of the Potent Antitubercular 2-(Decylsulfonyl)acetamide is Less Active Against Mycobacterium tuberculosis, but a More Potent Antistaphylococcal Agent

Australian Journal of Chemistry, 2018

Due to the prevalence of thioamides in antibacterial compounds, we chose to convert the amide in ... more Due to the prevalence of thioamides in antibacterial compounds, we chose to convert the amide in the antitubercular compound 2-(decylsulfonyl)acetamide to a thioamide using Lawesson’s reagent to study its activity against a range of microorganisms. This derivative (8) had significantly diminished activity against tuberculosis but slightly better activity than the parent compound against the Gram positive species Staphylococcus aureus. This activity against a second major pathogen is remarkable considering the structural simplicity of these compounds.

Research paper thumbnail of Crystallization-induced amide bond formation creates a boron-centered spirocyclic system

Heterocyclic Communications, 2017

The 5-nitrosalicylate ester of 2-acetamidophenylboronic acid (C15H10BN2O6) is formed under crysta... more The 5-nitrosalicylate ester of 2-acetamidophenylboronic acid (C15H10BN2O6) is formed under crystallization conditions from the 5-nitrosalicylate ester of 2-aminophenylboronic acid. The boron at the center of this structure exists as a tetrahedral complex produced by a dative bond with the amide carbonyl. The perpendicular shape produces an unusual packing structure including a bifurcated hydrogen bond between the amide hydrogen and carbonyl groups on two neighboring molecules. We propose that this reaction occurs due to increased Lewis acidity of the nitrosalicylate ester of 2-aminophenylboronic acid.

Research paper thumbnail of Glyconanoparticles for targeting macrophages to deliver therapeutic agents

Bacterial infection is still one of the leading causes of hospitalization and mortality, although... more Bacterial infection is still one of the leading causes of hospitalization and mortality, although antibiotics are used comprehensively to treat the infectious diseases. The clinical failure of antibiotic therapy is associated with low bioavailability, poor penetration capacity to bacterial infection sites, the side effect of antibiotics, and the antibiotic resistance properties of bacteria. Moreover, many deadly infectious diseases are produced by microorganisms that are able to survive in macrophages. The intracellular location of these pathogens protects them from the host defence systems and from some antibiotics with poor penetration into macrophages. Therefore, the use of non-viral nanoparticulate systems for the delivery of therapeutic agents is receiving considerable attention to improve the penetration of drugs into macrophages as well as the use of specific target molecules onto the nanocarrier systems that deliver these drugs directly to the target cell. These systems can ...

Research paper thumbnail of Direct Mitsunobu monoesterification of N-protected tobramycin competes with intramolecular pyrrolidine formation in ester prodrug synthesis

Carbohydrate Research, 2015

Unlike the related aminoglycoside neomycin B, N-protected tobramycin can be selectively esterifie... more Unlike the related aminoglycoside neomycin B, N-protected tobramycin can be selectively esterified at its sole, primary hydroxyl group under Mitsunobu conditions. However, depending on the reaction conditions, the reaction can take a different course with intramolecular cyclization of an N-Boc amine leading to formation of an unusual tobramycin pyrrolidine derivative as the major reaction product.

Research paper thumbnail of Methyl 2,3,4-tri- O -acetyl-1-azido-1-deoxy-β- D -glucopyranuronate at room temperature

Acta Crystallographica Section E Structure Reports Online, 2005

Research paper thumbnail of Working in triads: A case study of a peer review process

Journal of University Teaching and Learning Practice

Peer review of teaching has become an accepted educational procedure in Australia to quality assu... more Peer review of teaching has become an accepted educational procedure in Australia to quality assure the quality of teaching practices. The institutional implementation of the peer review process can be viewed as genuine desire to improve teaching quality or an imposition from above as a measure of accountability and performativity. One approach is to conduct the peer review process as a team or a triad, involving a group of three academics. This article reviews this process of peer review through the eyes of the participants. The results of the study indicate that the peer review process upon which this study is based, has the potential to not only significantly impact academics’ pedagogy but to improve teaching confidence and associated benefits in regard to evidence based teaching for promotional opportunities.

Research paper thumbnail of Facile amidinations of 2-aminophenylboronic acid promoted by boronate ester formation

Organic & Biomolecular Chemistry

Amidine synthesis by amine addition to nitriles normally requires high temperatures or harsh cata... more Amidine synthesis by amine addition to nitriles normally requires high temperatures or harsh catalysts. Here, we report that boronate esters can facilitate amidination of proximal amines with moderate heating. With...

Research paper thumbnail of A Simple Glycolipid Mimic of the Phosphatidylinositol Mannoside Core from Mycobacterium tuberculosis Inhibits Macrophage Cytokine Production

Chembiochem : a European journal of chemical biology, Jan 25, 2018

Glycolipids from Mycobacterium tuberculosis have a profound impact on the innate immune response ... more Glycolipids from Mycobacterium tuberculosis have a profound impact on the innate immune response of the host. Macrophage-inducible C-type lectin (Mincle) is a pattern-recognition receptor that has been shown to bind trehalose dimycolate (TDM) from the mycobacterium and instigate intracellular signalling in the immune cell. There are structural similarities between the structures of TDM and phosphatidyl inositol mannoside (PIM). We thus hypothesized that these latter structures might also modulate an immune response in a similar manner. To test this, we synthesized a series of new mannose derivatives modified with fatty esters at the 6-position and assessed the release of inflammatory cytokines in human U937 macrophages under the induction of lipopolysaccharides (LPS) after glycolipid treatment. The results showed that the amount of two major cytokines-tumour necrosis factor (TNF)-α and interleukin (IL)-6-released from LPS-stimulated U937 cells decreased significantly when compared t...

Research paper thumbnail of Back to (non-)Basics: An Update on Neutral and Charge-Balanced Glycosidase Inhibitors

Mini reviews in medicinal chemistry, Jan 2, 2017

Glycosidases have important anti-cancer, anti-viral and anti-diabetic properties. This review cov... more Glycosidases have important anti-cancer, anti-viral and anti-diabetic properties. This review covers the literature in the past 15 years since our initial review in this journal on "neutral" glycosidase inhibitors lacking a basic nitrogen found in iminosugars and azasugars or inhibitors that are neutral by virtue of being "charge-balanced" (zwitterionic). These structurally diverse inhibitors include lactones, lactams, epoxides such as cyclophellitol, and sulfonium ion derivatives of the natural product salacinol. Synthetic efforts toward cyclophillitol, salicinol and derivatives are also highlighted. Importantly, certain metals can inhibit glycosidases and care must be taken to remove residual catalysts from synthetic material to be tested against these enzymes.

Research paper thumbnail of Tapping into Boron/a-Hydroxycarboxylic Acid Interactions in Sensing and Catalysis

Research paper thumbnail of Synthesis of C-glycosylated compounds with the use of a mild, iodine-catalyzed reaction

Research paper thumbnail of Boronic Acid Receptors for α-Hydroxycarboxylates: High Affinity of Shinkai's Glucose Receptor for Tartrate

The Journal of Organic Chemistry, Jul 1, 2002

Research paper thumbnail of Glycoside compounds and methods of synthesis

Research paper thumbnail of 3a-Azido-5-cholestene

Acta Crystallogr E Struct Rep, 2008

Research paper thumbnail of Ethyl 3�-hydroxypregna-5,17(20)-dien-21-oate

Acta Crystallogr E Struct Rep, 2006

Research paper thumbnail of 4-Hydroxy­methyl-1-(2,3,4,6-tetra-O-acetyl--D-glucopyranos­yl)-1,2,3-triazole

Research paper thumbnail of ChemInform Abstract: Iodine-Catalyzed Ferrier Reaction. Part 1. A Mild and Highly Versatile Glycosylation of Hydroxyl and Phenolic Groups

ChemInform, 1995

ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance t... more ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Research paper thumbnail of Boronic acid receptors for alpha-hydroxycarboxylates: high affinity of Shinkai's glucose receptor for tartrate

The Journal of organic chemistry, Jan 26, 2002

The glucose receptor 1 developed by Shinkai was synthesized by known methods and with modificatio... more The glucose receptor 1 developed by Shinkai was synthesized by known methods and with modifications involving the final synthetic step, installation of the phenylboronic acid moieties. Binding of the bis(alpha-hydroxycarbolxylate), tartrate, was assessed and compared to the corresponding bis(diol), erythritol, as well as the corresponding mono(alpha-hydoxycarboxylate), malate. These results suggest that bisboronate/bis(alpha-hydoxycarboxylate) interactions are stronger than the corresponding bisboronate/bis(diol) interactions. Furthermore, we report that the receptor is an order of magnitude more selective for tartrate than malate.

Research paper thumbnail of Design and Synthesis of Boronolectin Fluorescence Sensors

This thesis reports on the use of the element boron in organic chemistry. Its role in catalysis, ... more This thesis reports on the use of the element boron in organic chemistry. Its role in catalysis, as well as its broad utility when in the form of a boronic acid functional group is demonstrated. Boric acid and boronic acids have applications in numerous kinds of chemical reactions as catalysts. Boric acid is demonstrated in this work to catalyse the esterification of a- hydroxycarboxylic acid starting materials, including carbohydrates, typically in excellent yield. A series of reactions were conducted to demonstrate the utility and limitations of this technique. Included in this work is the synthesis of the carbohydrate, KDO. Furthermore, a series of esters were generated using salicylic acid as a starting material, one of which was subjected to x-ray crystallographic studies. Also in this thesis a novel type of boronic acid catalysed amide forming reaction is described. The reaction is shown to proceed rapidly under mild reaction conditions with little purification required to giv...

Research paper thumbnail of Carbohydrate-based nanocarriers and their application to target macrophages and deliver antimicrobial agents

Advanced Drug Delivery Reviews, 2019

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Research paper thumbnail of Thioamide Derivative of the Potent Antitubercular 2-(Decylsulfonyl)acetamide is Less Active Against Mycobacterium tuberculosis, but a More Potent Antistaphylococcal Agent

Australian Journal of Chemistry, 2018

Due to the prevalence of thioamides in antibacterial compounds, we chose to convert the amide in ... more Due to the prevalence of thioamides in antibacterial compounds, we chose to convert the amide in the antitubercular compound 2-(decylsulfonyl)acetamide to a thioamide using Lawesson’s reagent to study its activity against a range of microorganisms. This derivative (8) had significantly diminished activity against tuberculosis but slightly better activity than the parent compound against the Gram positive species Staphylococcus aureus. This activity against a second major pathogen is remarkable considering the structural simplicity of these compounds.

Research paper thumbnail of Crystallization-induced amide bond formation creates a boron-centered spirocyclic system

Heterocyclic Communications, 2017

The 5-nitrosalicylate ester of 2-acetamidophenylboronic acid (C15H10BN2O6) is formed under crysta... more The 5-nitrosalicylate ester of 2-acetamidophenylboronic acid (C15H10BN2O6) is formed under crystallization conditions from the 5-nitrosalicylate ester of 2-aminophenylboronic acid. The boron at the center of this structure exists as a tetrahedral complex produced by a dative bond with the amide carbonyl. The perpendicular shape produces an unusual packing structure including a bifurcated hydrogen bond between the amide hydrogen and carbonyl groups on two neighboring molecules. We propose that this reaction occurs due to increased Lewis acidity of the nitrosalicylate ester of 2-aminophenylboronic acid.

Research paper thumbnail of Glyconanoparticles for targeting macrophages to deliver therapeutic agents

Bacterial infection is still one of the leading causes of hospitalization and mortality, although... more Bacterial infection is still one of the leading causes of hospitalization and mortality, although antibiotics are used comprehensively to treat the infectious diseases. The clinical failure of antibiotic therapy is associated with low bioavailability, poor penetration capacity to bacterial infection sites, the side effect of antibiotics, and the antibiotic resistance properties of bacteria. Moreover, many deadly infectious diseases are produced by microorganisms that are able to survive in macrophages. The intracellular location of these pathogens protects them from the host defence systems and from some antibiotics with poor penetration into macrophages. Therefore, the use of non-viral nanoparticulate systems for the delivery of therapeutic agents is receiving considerable attention to improve the penetration of drugs into macrophages as well as the use of specific target molecules onto the nanocarrier systems that deliver these drugs directly to the target cell. These systems can ...

Research paper thumbnail of Direct Mitsunobu monoesterification of N-protected tobramycin competes with intramolecular pyrrolidine formation in ester prodrug synthesis

Carbohydrate Research, 2015

Unlike the related aminoglycoside neomycin B, N-protected tobramycin can be selectively esterifie... more Unlike the related aminoglycoside neomycin B, N-protected tobramycin can be selectively esterified at its sole, primary hydroxyl group under Mitsunobu conditions. However, depending on the reaction conditions, the reaction can take a different course with intramolecular cyclization of an N-Boc amine leading to formation of an unusual tobramycin pyrrolidine derivative as the major reaction product.

Research paper thumbnail of Methyl 2,3,4-tri- O -acetyl-1-azido-1-deoxy-β- D -glucopyranuronate at room temperature

Acta Crystallographica Section E Structure Reports Online, 2005

Research paper thumbnail of Working in triads: A case study of a peer review process

Journal of University Teaching and Learning Practice

Peer review of teaching has become an accepted educational procedure in Australia to quality assu... more Peer review of teaching has become an accepted educational procedure in Australia to quality assure the quality of teaching practices. The institutional implementation of the peer review process can be viewed as genuine desire to improve teaching quality or an imposition from above as a measure of accountability and performativity. One approach is to conduct the peer review process as a team or a triad, involving a group of three academics. This article reviews this process of peer review through the eyes of the participants. The results of the study indicate that the peer review process upon which this study is based, has the potential to not only significantly impact academics’ pedagogy but to improve teaching confidence and associated benefits in regard to evidence based teaching for promotional opportunities.

Research paper thumbnail of Facile amidinations of 2-aminophenylboronic acid promoted by boronate ester formation

Organic & Biomolecular Chemistry

Amidine synthesis by amine addition to nitriles normally requires high temperatures or harsh cata... more Amidine synthesis by amine addition to nitriles normally requires high temperatures or harsh catalysts. Here, we report that boronate esters can facilitate amidination of proximal amines with moderate heating. With...

Research paper thumbnail of A Simple Glycolipid Mimic of the Phosphatidylinositol Mannoside Core from Mycobacterium tuberculosis Inhibits Macrophage Cytokine Production

Chembiochem : a European journal of chemical biology, Jan 25, 2018

Glycolipids from Mycobacterium tuberculosis have a profound impact on the innate immune response ... more Glycolipids from Mycobacterium tuberculosis have a profound impact on the innate immune response of the host. Macrophage-inducible C-type lectin (Mincle) is a pattern-recognition receptor that has been shown to bind trehalose dimycolate (TDM) from the mycobacterium and instigate intracellular signalling in the immune cell. There are structural similarities between the structures of TDM and phosphatidyl inositol mannoside (PIM). We thus hypothesized that these latter structures might also modulate an immune response in a similar manner. To test this, we synthesized a series of new mannose derivatives modified with fatty esters at the 6-position and assessed the release of inflammatory cytokines in human U937 macrophages under the induction of lipopolysaccharides (LPS) after glycolipid treatment. The results showed that the amount of two major cytokines-tumour necrosis factor (TNF)-α and interleukin (IL)-6-released from LPS-stimulated U937 cells decreased significantly when compared t...

Research paper thumbnail of Back to (non-)Basics: An Update on Neutral and Charge-Balanced Glycosidase Inhibitors

Mini reviews in medicinal chemistry, Jan 2, 2017

Glycosidases have important anti-cancer, anti-viral and anti-diabetic properties. This review cov... more Glycosidases have important anti-cancer, anti-viral and anti-diabetic properties. This review covers the literature in the past 15 years since our initial review in this journal on "neutral" glycosidase inhibitors lacking a basic nitrogen found in iminosugars and azasugars or inhibitors that are neutral by virtue of being "charge-balanced" (zwitterionic). These structurally diverse inhibitors include lactones, lactams, epoxides such as cyclophellitol, and sulfonium ion derivatives of the natural product salacinol. Synthetic efforts toward cyclophillitol, salicinol and derivatives are also highlighted. Importantly, certain metals can inhibit glycosidases and care must be taken to remove residual catalysts from synthetic material to be tested against these enzymes.

Research paper thumbnail of Tapping into Boron/a-Hydroxycarboxylic Acid Interactions in Sensing and Catalysis

Research paper thumbnail of Synthesis of C-glycosylated compounds with the use of a mild, iodine-catalyzed reaction

Research paper thumbnail of Boronic Acid Receptors for α-Hydroxycarboxylates: High Affinity of Shinkai's Glucose Receptor for Tartrate

The Journal of Organic Chemistry, Jul 1, 2002

Research paper thumbnail of Glycoside compounds and methods of synthesis

Research paper thumbnail of 3a-Azido-5-cholestene

Acta Crystallogr E Struct Rep, 2008

Research paper thumbnail of Ethyl 3�-hydroxypregna-5,17(20)-dien-21-oate

Acta Crystallogr E Struct Rep, 2006

Research paper thumbnail of 4-Hydroxy­methyl-1-(2,3,4,6-tetra-O-acetyl--D-glucopyranos­yl)-1,2,3-triazole

Research paper thumbnail of ChemInform Abstract: Iodine-Catalyzed Ferrier Reaction. Part 1. A Mild and Highly Versatile Glycosylation of Hydroxyl and Phenolic Groups

ChemInform, 1995

ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance t... more ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Research paper thumbnail of Boronic acid receptors for alpha-hydroxycarboxylates: high affinity of Shinkai's glucose receptor for tartrate

The Journal of organic chemistry, Jan 26, 2002

The glucose receptor 1 developed by Shinkai was synthesized by known methods and with modificatio... more The glucose receptor 1 developed by Shinkai was synthesized by known methods and with modifications involving the final synthetic step, installation of the phenylboronic acid moieties. Binding of the bis(alpha-hydroxycarbolxylate), tartrate, was assessed and compared to the corresponding bis(diol), erythritol, as well as the corresponding mono(alpha-hydoxycarboxylate), malate. These results suggest that bisboronate/bis(alpha-hydoxycarboxylate) interactions are stronger than the corresponding bisboronate/bis(diol) interactions. Furthermore, we report that the receptor is an order of magnitude more selective for tartrate than malate.