Cerebrovasculature refers to the network of blood vessels in the brain, and its coupling with neurons plays a critical role in regulating ion exchange, molecule transport, nutrient and oxygen delivery, and waste removal in the brain. Abnormalities in cerebrovasculature and disruptions of the blood supply are associated with a variety of cerebrovascular and neurodegenerative disorders. Nanocarriers, a nano-sized drug delivery system synthesized from various materials, have been designed to encapsulate therapeutic agents and overcome delivery challenges in crossing the blood-brain barrier (BBB) to achieve targeted and enhanced therapy for these diseases. Unraveling the transport of drugs and nanocarriers in the cerebrovasculature is important for pharmacokinetic and hemodynamic studies but is challenging due to difficulties in detecting these particles within the circulatory system of a live animal. In this dissertation, we developed a technique to achieve real-time in vivo tracking of nanocarriers in the cerebrovasculature using fluorescence correlation spectroscopy (FCS), which has great potential for determining the pharmacokinetics of drugs and nanocarriers, as well as for studying disease-related connections between the cerebrovascular and neurodegenerative diseases.

We utilized novel fluorescent probes composed of DNA-stabilized silver nanocluster (DNA-Ag₁₆NC), that emit in the first near-infrared window (NIR-I) upon two-photon excitation in the second NIR window (NIR-II), encapsulated in liposomes, which were then used to measure cerebral blood flow rates in live mice with high spatiotemporal resolution by two-photon in vivo FCS. Liposome encapsulation concentrated and protected DNA-Ag₁₆NCs from in vivo degradation, enabling the quantification of cerebral blood flow velocity within individual capillaries of a living mouse. We also loaded another DNA-stabilized silver nanocluster (DNA640), which exhibited higher quantum yield and anti-Stokes fluorescence upon upconversion absorption, into cationic mesoporous silica nanoparticles (CMSNs) and successfully coated them with liposomes. The cerebrovasculature was chronically labeled using an adeno-associated viral (AAV) vector encoding Alb-mNG secretion into the bloodstream, combined with FCS under upconversion excitation, enabling real-time observation of the flow velocity and particle number of DNA640-CMSN-liposomes within the capillaries. We applied our proposed techniques to study the cerebrovascular structure and blood flow velocity in Alzheimer's disease mouse models and to explore the effects of disease-related conditions on vasoconstriction and vasodilation.

KEYWORDS: Cerebrovascular, nanocarrier, FCS, NIR fluorescence, DNA-AgNC, in vivo

Zoom link: https://uky.zoom.us/j/5984755867?omn=87194697892

Meeting ID: 598 475 5867.

Cerebrovasculature refers to the network of blood vessels in the brain, and its coupling with neurons plays a critical role in regulating ion exchange, molecule transport, nutrient and oxygen delivery, and waste removal in the brain. Abnormalities in cerebrovasculature and disruptions of the blood supply are associated with a variety of cerebrovascular and neurodegenerative disorders. Nanocarriers, a nano-sized drug delivery system synthesized from various materials, have been designed to encapsulate therapeutic agents and overcome delivery challenges in crossing the blood-brain barrier (BBB) to achieve targeted and enhanced therapy for these diseases. Unraveling the transport of drugs and nanocarriers in the cerebrovasculature is important for pharmacokinetic and hemodynamic studies but is challenging due to difficulties in detecting these particles within the circulatory system of a live animal. In this dissertation, we developed a technique to achieve real-time in vivo tracking of nanocarriers in the cerebrovasculature using fluorescence correlation spectroscopy (FCS), which has great potential for determining the pharmacokinetics of drugs and nanocarriers, as well as for studying disease-related connections between the cerebrovascular and neurodegenerative diseases.

We utilized novel fluorescent probes composed of DNA-stabilized silver nanocluster (DNA-Ag₁₆NC), that emit in the first near-infrared window (NIR-I) upon two-photon excitation in the second NIR window (NIR-II), encapsulated in liposomes, which were then used to measure cerebral blood flow rates in live mice with high spatiotemporal resolution by two-photon in vivo FCS. Liposome encapsulation concentrated and protected DNA-Ag₁₆NCs from in vivo degradation, enabling the quantification of cerebral blood flow velocity within individual capillaries of a living mouse. We also loaded another DNA-stabilized silver nanocluster (DNA640), which exhibited higher quantum yield and anti-Stokes fluorescence upon upconversion absorption, into cationic mesoporous silica nanoparticles (CMSNs) and successfully coated them with liposomes. The cerebrovasculature was chronically labeled using an adeno-associated viral (AAV) vector encoding Alb-mNG secretion into the bloodstream, combined with FCS under upconversion excitation, enabling real-time observation of the flow velocity and particle number of DNA640-CMSN-liposomes within the capillaries. We applied our proposed techniques to study the cerebrovascular structure and blood flow velocity in Alzheimer's disease mouse models and to explore the effects of disease-related conditions on vasoconstriction and vasodilation.

KEYWORDS: Cerebrovascular, nanocarrier, FCS, NIR fluorescence, DNA-AgNC, in vivo

Zoom link: https://uky.zoom.us/j/5984755867?omn=87194697892

Meeting ID: 598 475 5867.

The health of our communities depends on the effective treatment of both solid and liquid waste to eradicate hazardous pollutants before they can interact with living organisms or contaminate the environment. Daily, society generates solid waste (commonly destined for landfills) and liquid waste, (commonly discharged into wastewater systems) and without proper treatment, these wastes can release hazardous primary secondary pollutants. Industries producing wastewater with high pollutant concentrations, especially those utilizing lignin-based biomass, face complex challenges because each facility may require a tailored treatment approach. In response, this work investigates the use of ozonolysis to transform lignin monomers into smaller, less hazardous components that can be more efficiently managed by public wastewater systems. Furthermore, while conventional wastewater treatment systems are effective for common water quality issues, they can inadvertently allow complex compounds, such pollutants from hospital effluent, to pass through. Under simulated treatment conditions incorporating sunlight and chlorination, a pollutant released from medical facilities is degraded, but this process may also lead to the formation of carcinogenic disinfection by-products (DBPs) that pose direct toxicological risks to nearby communities. The implications extend to solid waste management as well. Chemical phenomena, such as those occurring in poorly understood elevated temperature landfills (ETLFs), can compromise treatment methods and increase community exposure to harmful pollutants. By monitoring hazardous components, such as volatile organic compounds (VOCs), over time, this work aims to elucidate the chemical reactions occurring both during treatment and in the environment thereafter. Ultimately, this research underscores the need for fundamental, innovative approaches to pollution transformation. Bridging the gap between existing practices for solid and liquid waste treatment will be critical to safeguarding environmental and public health.

The health of our communities depends on the effective treatment of both solid and liquid waste to eradicate hazardous pollutants before they can interact with living organisms or contaminate the environment. Daily, society generates solid waste (commonly destined for landfills) and liquid waste, (commonly discharged into wastewater systems) and without proper treatment, these wastes can release hazardous primary secondary pollutants. Industries producing wastewater with high pollutant concentrations, especially those utilizing lignin-based biomass, face complex challenges because each facility may require a tailored treatment approach. In response, this work investigates the use of ozonolysis to transform lignin monomers into smaller, less hazardous components that can be more efficiently managed by public wastewater systems. Furthermore, while conventional wastewater treatment systems are effective for common water quality issues, they can inadvertently allow complex compounds, such pollutants from hospital effluent, to pass through. Under simulated treatment conditions incorporating sunlight and chlorination, a pollutant released from medical facilities is degraded, but this process may also lead to the formation of carcinogenic disinfection by-products (DBPs) that pose direct toxicological risks to nearby communities. The implications extend to solid waste management as well. Chemical phenomena, such as those occurring in poorly understood elevated temperature landfills (ETLFs), can compromise treatment methods and increase community exposure to harmful pollutants. By monitoring hazardous components, such as volatile organic compounds (VOCs), over time, this work aims to elucidate the chemical reactions occurring both during treatment and in the environment thereafter. Ultimately, this research underscores the need for fundamental, innovative approaches to pollution transformation. Bridging the gap between existing practices for solid and liquid waste treatment will be critical to safeguarding environmental and public health.

Graphical abstract:

Graphical abstract:

Biorefineries play a vital role in reducing dependence on fossil fuels and addressing global warming concerns. Unfortunately, investment in biorefineries remains limited due to economic sustainability concerns. One approach to enhance the economic viability of biorefineries is by fully utilizing the potential of feedstocks, particularly lignocellulosic biomass, which is commonly used in these processes. Traditional processing methods often alter the lignin portion of biomass, making it unsuitable for further utilization. However, when retained in its native form, lignin can serve as a valuable source of chemicals that contribute to the economic sustainability of biorefineries.

The lignin-first approach, which removes lignin from the cellulosic portion before biofuel conversion, allows for the recovery of value-added chemicals from lignin and enhances the sustainability of biorefineries. One common method for implementing this approach is organosolv, which removes the lignin from biomass. This research developed an organosolv pretreatment method to isolate syringaresinol (S-β-β'-S), a lignin-derived dimer with various biomedical and industrial applications, from oak sawdust as the source biomass. The method incorporated a heat treatment step to increase syringaresinol yields, and key treatment parameters were optimized for maximum output. This approach was then applied to other biomass types: hardwood, softwood, and grass. Poplar and hemp were identified as alternative sources of syringaresinol. The method also revealed the presence of several other potential value-added compounds in the biomass types investigated.

Additionally, this research established a linear retention index (LRI) for the gas chromatographic (GC) analysis of 25 common lignin-derived monomers and dimers, which are frequently detected in biomass chromatograms after pretreatments like organosolv. LRI values are independent of column characteristics, enabling unambiguous identification of analytes and ensuring reproducibility in experimental results. These calculated values were validated with a second GC system. The LRI facilitates the identification and confirmation of compounds without the need for mass spectrometric (MS) analysis, allowing for comparison of chromatographic results across multiple GC systems and aiding in the prediction of retention times for these compounds.

While extracting value-added compounds like syringaresinol from biomass is the first step, recovering them from complex reaction mixtures presents additional challenges. This study explored the use of cyclodextrins (CDs) as potential recovery materials for syringaresinol. CDs are conical molecules with a hydrophilic exterior and a hydrophobic cavity, which can selectively capture lignans through guest-host complex interactions. Initial high-performance liquid chromatography (HPLC) analysis with a commercial β-CD column revealed that lignans, particularly syringaresinol and pinoresinol interact more strongly with β-CD than with most other monomeric lignin decomposition products. Furthermore, the study suggested that γ-CD might be a better recovery material for syringaresinol compared to β-CD. To test this hypothesis, a modified frontal analysis continuous capillary electrophoresis (FACCE) method was developed and validated as an inexpensive, simple approach to estimate the binding constants of lignans to CDs. The FACCE method provided insights into the interactions between lignans and CDs, facilitating the selection of the potentially suitable CD-type for recovery.

Biorefineries play a vital role in reducing dependence on fossil fuels and addressing global warming concerns. Unfortunately, investment in biorefineries remains limited due to economic sustainability concerns. One approach to enhance the economic viability of biorefineries is by fully utilizing the potential of feedstocks, particularly lignocellulosic biomass, which is commonly used in these processes. Traditional processing methods often alter the lignin portion of biomass, making it unsuitable for further utilization. However, when retained in its native form, lignin can serve as a valuable source of chemicals that contribute to the economic sustainability of biorefineries.

The lignin-first approach, which removes lignin from the cellulosic portion before biofuel conversion, allows for the recovery of value-added chemicals from lignin and enhances the sustainability of biorefineries. One common method for implementing this approach is organosolv, which removes the lignin from biomass. This research developed an organosolv pretreatment method to isolate syringaresinol (S-β-β'-S), a lignin-derived dimer with various biomedical and industrial applications, from oak sawdust as the source biomass. The method incorporated a heat treatment step to increase syringaresinol yields, and key treatment parameters were optimized for maximum output. This approach was then applied to other biomass types: hardwood, softwood, and grass. Poplar and hemp were identified as alternative sources of syringaresinol. The method also revealed the presence of several other potential value-added compounds in the biomass types investigated.

Additionally, this research established a linear retention index (LRI) for the gas chromatographic (GC) analysis of 25 common lignin-derived monomers and dimers, which are frequently detected in biomass chromatograms after pretreatments like organosolv. LRI values are independent of column characteristics, enabling unambiguous identification of analytes and ensuring reproducibility in experimental results. These calculated values were validated with a second GC system. The LRI facilitates the identification and confirmation of compounds without the need for mass spectrometric (MS) analysis, allowing for comparison of chromatographic results across multiple GC systems and aiding in the prediction of retention times for these compounds.

While extracting value-added compounds like syringaresinol from biomass is the first step, recovering them from complex reaction mixtures presents additional challenges. This study explored the use of cyclodextrins (CDs) as potential recovery materials for syringaresinol. CDs are conical molecules with a hydrophilic exterior and a hydrophobic cavity, which can selectively capture lignans through guest-host complex interactions. Initial high-performance liquid chromatography (HPLC) analysis with a commercial β-CD column revealed that lignans, particularly syringaresinol and pinoresinol interact more strongly with β-CD than with most other monomeric lignin decomposition products. Furthermore, the study suggested that γ-CD might be a better recovery material for syringaresinol compared to β-CD. To test this hypothesis, a modified frontal analysis continuous capillary electrophoresis (FACCE) method was developed and validated as an inexpensive, simple approach to estimate the binding constants of lignans to CDs. The FACCE method provided insights into the interactions between lignans and CDs, facilitating the selection of the potentially suitable CD-type for recovery.

The Department of Chemistry hosts an annual Graduation Celebration and Awards Ceremony to recognize the outstanding achievements of our students on an annual basis.

We invite families and friends of graduates and award winners to join us in celebrating the success of these outstanding students. A reception will be held after the ceremony. 

To view this year's brochure, click here. For past events, click here.

College of Arts and Sciences Awards

Outstanding Teaching Assistant in the Department of Chemistry | Shuvo Deb Nath

Graduate Student Awards

100% Plus Award | Lateefat Jimoh

Outstanding Graduate Student Research Award | Kathryn Pitton

Outstanding Teaching Assistant Award | Md Tawabur Rahman & Motunrayo Oladele

William D. Ehmann Graduate Award Fund in Chemistry | Shickshitha Dissanayake

C.H.H. Griffith Outstanding General Chemistry TA Award | Deborah Adeyemi-Alabi & Alexander Igwebuike

Fast Start Award | Joy Jerome

Undergraduate Student Awards

100% Plus Award | Lauren Gravatte

Hammond Undergraduate Service Award | Walter Kunnmann

Hammond Leadership Award | Shasanka Lamichhane

Nancy J. Stafford Award | Mason Marrs

Willard R. Meredith Memorial Award | Marissa Harris

First-Year Chemistry Major Award | Isabella Soon

General Chemistry Excellence Award (Spring 2024) | Thomas Lockhart, Elizabeth Scheetz & Caralea Vest

General Chemistry Excellence Award (Fall 2024) | Harsh Patel & Lauren Marksbury

Undergraduate Scholarships

Wilbur L. Price Scholarship | Daani Karim

The Department of Chemistry hosts an annual Graduation Celebration and Awards Ceremony to recognize the outstanding achievements of our students on an annual basis.

We invite families and friends of graduates and award winners to join us in celebrating the success of these outstanding students. A reception will be held after the ceremony. 

To view this year's brochure, click here. For past events, click here.

College of Arts and Sciences Awards

Outstanding Teaching Assistant in the Department of Chemistry | Shuvo Deb Nath

Graduate Student Awards

100% Plus Award | Lateefat Jimoh

Outstanding Graduate Student Research Award | Kathryn Pitton

Outstanding Teaching Assistant Award | Md Tawabur Rahman & Motunrayo Oladele

William D. Ehmann Graduate Award Fund in Chemistry | Shickshitha Dissanayake

C.H.H. Griffith Outstanding General Chemistry TA Award | Deborah Adeyemi-Alabi & Alexander Igwebuike

Fast Start Award | Joy Jerome

Undergraduate Student Awards

100% Plus Award | Lauren Gravatte

Hammond Undergraduate Service Award | Walter Kunnmann

Hammond Leadership Award | Shasanka Lamichhane

Nancy J. Stafford Award | Mason Marrs

Willard R. Meredith Memorial Award | Marissa Harris

First-Year Chemistry Major Award | Isabella Soon

General Chemistry Excellence Award (Spring 2024) | Thomas Lockhart, Elizabeth Scheetz & Caralea Vest

General Chemistry Excellence Award (Fall 2024) | Harsh Patel & Lauren Marksbury

Undergraduate Scholarships

Wilbur L. Price Scholarship | Daani Karim