Project Title
Spectroscopy‑at‑IKU: Manipulating and Characterizing Molecular Architectures: from Isolated Molecules to Molecular Crystals
Project Summary
The project aims to establish an internationally competitive molecular spectroscopy research hub at Istanbul Kültür University through the ERA Chairs programme. It focuses on molecular physics, chemistry and materials science by creating advanced spectroscopy infrastructure, attracting world-class researchers, and training young scientists. Research is centered on two themes: (i) molecular structure, spectroscopy and reactivity of isolated molecules relevant to atmospheric and astrochemistry, and (ii) polymorphism and co-crystallization of molecular crystals for pharmaceutical applications. The project also strengthens collaboration with academia and industry while increasing IKU's international research capacity.
Project Title
Gas-to-Solid Pathways and Reactivity of Isoniazid–Pyrazinamide Co-Crystals
Project Summary
Co-crystallization is an effective strategy to tailor the physicochemical properties of active pharmaceutical ingredients without altering their molecular identity. Although isoniazid and pyrazinamide are well-established antitubercular agents, the behaviour of their co-crystal under sublimation, cryogenic trapping, and irradiation remains largely unexplored. This project integrates conventional solid-state characterization (infrared and Raman spectroscopy, differential scanning calorimetry, single-crystal X-ray diffraction) with advanced low-temperature matrix isolation, neat-vapour deposition, and UV photolysis, supported by density functional theory calculations. By sublimating the INH–PZA co-crystal and trapping the vapour at 10 K, we will determine whether supramolecular units persist in the gas phase or dissociate, and how they reorganize upon annealing or direct deposition without an inert matrix. Ultraviolet photolysis using various light sources, including diode-laser-based systems and tuneable laser systems (pumping laser + MOPO) will probe the light-induced processes for both the matrix-isolated and different solid materials. This integrated approach bridges pharmaceutical co-crystal chemistry with fundamental gas-phase and matrix isolation studies, delivering unprecedented insight into intermolecular bonding, sublimation dynamics, and photo-reactivity, and informing rational strategies for controlling drug solid forms through vapour-phase processes.
Project Title
Utilization of Saccharin Waste within a Circular Economy Framework through Pharmaceutical Co-Crystallization with Isoniazid
Project Summary
Saccharin, a widely utilized artificial sweetener, often becomes part of industrial and consumer waste, presenting environmental challenges due to its chemical persistence and limited biodegradability. This study introduces an innovative recycling approach that adheres to circular economy principles by converting saccharin waste into high-value pharmaceutical materials. Specifically, saccharin is upcycled through co-crystallization with isoniazid (INH), a well-established antitubercular drug. This process not only enhances the physicochemical properties of the active pharmaceutical ingredient but also transforms saccharin from a pollutant into a functional component of drug delivery systems. The study examines the behavior of INH–SAC co-crystals under conditions of sublimation, cryogenic trapping, and photonic excitation, employing advanced analytical techniques such as infrared and Raman spectroscopy, differential scanning calorimetry, and single-crystal X-ray diffraction. These experimental investigations are augmented by density functional theory (DFT) calculations to elucidate molecular interactions and stability. Sublimation and matrix isolation at 10 K are utilized to determine whether supramolecular structures persist or undergo reorganization during phase transitions. Furthermore, ultraviolet photolysis using diode-laser and tunable laser systems is employed to explore light-induced transformations in both isolated and solid states. This comprehensive approach illustrates how vapor-phase engineering and supramolecular chemistry can facilitate the sustainable recycling of saccharin waste. By transforming a low-value, environmentally persistent compound into a functional pharmaceutical co-crystal, the study contributes to waste valorization and supports the advancement of green technologies within the pharmaceutical sector.
Project Title
Mechanical, Chemical, and Spectroscopic Analysis of the Repair of Different Limestone Types Used in the Construction of Historical Structures by Using the Bacterial Carbonate Precipitation Method
Project Summary
The effectiveness of microbially induced calcium carbonate precipitation (MICP) may vary depending on the mineralogical characteristics of the treated stone. Accordingly, this study investigates the performance of microbiological surface improvement in limestones with different clay contents, with particular emphasis on the possible influence of clay minerals on microbial mineralization and calcium carbonate formation. Within this scope, Bacillus subtilis and Bacillus sphaericus strains were applied by brushing onto Süloğlu, Kefken, and Pınarhisar limestones, which have different clay contents. To determine the changes in the physical, mechanical, mineralogical, and microstructural properties of the stones before and after microbiological surface improvement, ultrasonic pulse velocity and compressive strength tests were carried out together with Raman spectroscopy, Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and X-ray diffraction (XRD) analyses. These analyses enabled the evaluation of the distribution and mineralogical characteristics of calcium carbonate formations resulting from bacterial activity, together with their effects on the mechanical and physical properties of the stones. Based on the findings obtained, the study aims to reveal the relationship between the clay content of limestone and the effectiveness of microbiological surface improvement, as well as to compare the responses of different limestone types to MICP treatment. In this way, the study is expected to contribute to the development of environmentally friendly and sustainable biological consolidation approaches for the conservation of limestone used in cultural heritage structures, while also taking the mineralogical characteristics of the material into consideration.
Project Title
Preparation and Characterization of Coaxial Nanofibers Suitable for Transdermal Applications, with a Methacrylate Copolymer Shell and an Oregano Oil–PEG1000 Core, and Investigation of Oregano Oil Release Kinetics
Project Title
Design, Fabrication, and Validation of a Laboratory-Scale Apparatus for Co-Crystal Synthesis via the Spray-Drying Method
Project Summary
Cocrystal synthesis, widely used in pharmaceutical applications, is one of the methods employed to enhance properties such as drug stability, solubility, and dissolution rate, as well as to reduce the harmful effects of pharmaceutical components. However, it involves highly challenging and complex chemical processes. This project aims to design, manufacture, and validate a device that will enable the laboratory-scale production of pharmaceutical cocrystals using the spray-drying method. The system will consist of a glass drying chamber, a two-fluid nozzle, a closed-loop structure suitable for safe operation with organic solvents, a cyclone separator, a HEPA filtration unit, and microcontroller-based control and safety modules. The originality of the project lies in the development of a domestic, low-cost prototype for a technology that is currently accessible in our country only through expensive imported devices, thereby contributing a novel capability to university-level research. Within the scope of the project, cocrystals containing anti-tuberculosis active pharmaceutical ingredients (APIs) synthesized at IKU-SPECTRA and their formation mechanisms will be taken into account for the validation of the laboratory-scale spray-drying device to be developed. Additionally, new anti-tuberculosis cocrystals will be synthesized using this device, and the production parameters will be optimized. At the end of the project, it is planned to file a patent application for the designed device prototype. With its compact and portable structure, the prototype will be introduced into the university's R&D infrastructure as a domestic, low-cost piece of equipment. Thanks to its inert closed-loop system, the improvement of occupational safety and environmental performance will also be among the project outcomes.
Project Title
In Vitro and In Vivo Evaluation of DAPT and MK-0752 Notch Inhibitors with Dexamethasone in Nano-flower and Co-Crystal Forms in T-Cell Acute Lymphoblastic Leukemia (T-ALL), a Rare Hematological Malignancy
Project Summary
T-cell acute lymphoblastic leukemia (T-ALL) is a rare and aggressive hematological malignancy characterized by uncontrolled proliferation associated with disrupted T-cell developmental stages in the thymus. NOTCH1 mutations, frequently observed in a significant proportion of patients, lead to ligand-independent constitutive activation of the Notch signaling pathway, promoting both cellular proliferation and anti-apoptotic processes, thereby increasing treatment resistance. The central role of the Notch axis rationalizes targeting with γ-secretase inhibitors (GSIs; DAPT and MK-0752); however, constitutive NICD production and intracellular escape mechanisms can limit GSI efficacy. Meanwhile, dexamethasone (DEX), a clinically essential component, induces cell death in T-lymphoblasts by activating pro-apoptotic genes via the glucocorticoid receptor pathway. However, disruptions in NR3C1 levels and Notch-mediated signaling changes contribute to glucocorticoid resistance, increasing relapse risk. This project aims to overcome resistance and enhance the therapeutic index in T-ALL by co-delivering DEX with GSIs within microarchitectures that localize drugs at cell-cell (juxtacrine) contact sites. To achieve this, two complementary formulation platforms will be developed: (i) drug-inorganic hybrid nano-flowers (hNFs) and (ii) binary co-crystals. Single and dual combinations of DEX, DAPT, and MK-0752 will be used with Cu²⁺ ions to synthesize DEX@Cu²⁺ hNF, DAPT@Cu²⁺ hNF, MK0752@Cu²⁺ hNF, DAPT-DEX@Cu²⁺ hNF, and MK0752-DEX@Cu²⁺ hNF, followed by structural/morphological characterization and biological stability analyses. In parallel, DEX:DAPT and MK0752:DEX co-crystals will be produced via slow evaporation; solubility and stability improvements will be evaluated through theoretical and experimental validation. These systems are designed to enhance solubility and bioavailability while reducing toxicity and systemic exposure, preserving combination synergy. In the in vitro phase, formulations will be systematically assessed through cell viability assays and biomarkers such as Notch receptor expression and NR3C1 autoregulation. Drug interactions will be quantitatively analyzed using Bliss, HSA, and Loewe models to generate synergy profiles. For in vivo validation, tumor progression and toxicity parameters will be concurrently evaluated in zebrafish models. These juxtacrine-targeted therapeutic architectures are expected to enhance local drug accumulation, achieving similar or superior efficacy with lower overall doses, enabling dose sparing and resensitization potential, particularly for DEX. The anticipated outcome is preclinical evidence of a combination strategy integrating DAPT/MK-0752/DEX within nano-flower and co-crystal platforms, offering high specificity, low toxicity, and strong synergy in T-ALL with translational potential. By targeting juxtacrine interactions at the core of Notch-dependent pathobiology, this project will fill a gap in the literature and provide a robust foundation for future translational studies.
Project Title
Investigation of the Effect of Innovative Curcumin@Inorganic Hybrid Nanoflower Therapies Combined with Presenilin Inhibitors on Neural Differentiation and Alzheimer's Disease in the SH-SY5Y Cell Model
Project Summary
Alzheimer's disease (AD) is one of the major neurodegenerative disorders for which no curative treatment currently exists, arising from the interplay of age-related degenerative processes, genetic predisposition, and environmental factors. In familial forms of the disease, mutations in presenilin 1 (PSEN1), presenilin 2 (PSEN2), and amyloid precursor protein (APP) alter the substrate specificity of the γ-secretase complex, leading to excessive production of pathological amyloid-β (Aβ) species. However, γ-secretase is also the main catalytic component of the Notch signaling pathway, which plays essential roles in cell differentiation, proliferation, and apoptosis. Therefore, therapeutic use of γ-secretase inhibitors requires a delicate balance between efficacy and toxicity. In recent years, natural compounds and nanobiotechnological approaches have offered promising strategies to achieve this balance. Curcumin, with its polyphenolic structure and multiple mechanisms of action, has emerged as a potent neuroprotective candidate by simultaneously targeting Aβ accumulation, oxidative stress, and neuroinflammation. Nevertheless, its poor bioavailability limits clinical applicability. To overcome this limitation, organic–inorganic hybrid nanoflower (hNF) structures—first discovered in 2012—present an ideal carrier system due to their high surface area, porosity, biocompatibility, and low toxicity. In these structures, proteins or natural organic molecules interact with metal ions (e.g., Cu²⁺, Zn²⁺), forming flower-like architectures. Within this project, curcumin-based hybrid nanoflowers (K@Cu²⁺ hNF and K@Zn²⁺ hNF) will be synthesized and characterized using curcumin in combination with Cu²⁺ and Zn²⁺ ions. Their biological effects will be evaluated in human neuroblastoma SH-SY5Y cells and their neuronally differentiated derivatives, in which an Alzheimer's disease model will be established. Aβ aggregation will be confirmed using Congo red staining, while cell viability, neurotoxicity, neuroprotection, and gene expression profiles will be assessed through multidimensional analyses. Additionally, combinations of curcumin-hNFs with γ-secretase inhibitors DAPT and MK-0752 will be examined, and synergistic effects will be quantified using Bliss, HSA, and Loewe interaction models. This approach aims to contribute to the development of next-generation combination therapies that are pathway-specific while minimizing toxicity. The project not only provides a strong platform for elucidating the molecular mechanisms underlying Alzheimer's disease in Türkiye but also seeks to produce clinically translatable, innovative solutions through nanoflower-based curcumin formulations. The study aligns with the goals of the Twelfth Development Plan in the fields of health technologies and biotechnology, contributing to scientific capacity building and the advancement of innovative therapeutics. Erciyes University, where the project will be conducted, is among the top ten universities designated as Research Universities and possesses well-established research centers and infrastructure suitable for such studies. The advisor, Prof. Dr. Nalan ÖZDEMİR, has extensive experience, projects, and high-impact international publications on the synthesis and biocatalytic applications of organic–inorganic hybrid nanoflowers. The biochemistry research laboratory used by the advisor has sufficient chemical materials and laboratory equipment required for the execution of the proposed studies.
