Directory: Faculty

Ilya Zharov

Ilya Zharov

ORGANIC, INORGANIC & MATERIALS CHEMISTRY

Assistant Professor

B.Sc. (Hons), Chelyabink State University, 1990
M.Sc., Technion – Israel Institute of Technology, 1994
Ph.D., University of Colorado at Boulder, 2000
Beckman Postdoctoral Fellow, University of Illinois at Urbana-Champaign, 2000-2003

Phone: (801) 587-9335

Office: 3416 HEB-S

Email: i.zharov@utah.edu

Research Group

Publications

Activities & Awards

Research Interests

SEM images of the chemically-modified opal

Figure 1. SEM images of the chemically-modified colloidal film prepared from 440 nm diameter silica spheres (A) top view, the geometric projection of a pore observed from the (111) plane is outlined in the inset. (B) Side view. (C) A scheme of its permselective behavior.

We are working in three main areas. The focus of the first area is on responsive inorganic nanopores. In particular, we work on the preparation and study of nanoporous colloidal materials. Synthetic colloidal crystals form via self-assembly of nanoscale-sized silica spheres into a close-packed face-centered cubic lattice and contain highly ordered arrays of three-dimensional interconnected pores 5-100 nm in size (Figure 1). We use nanoporous colloidal films, membranes and microfluidic channels for size-selective transport of drug molecules and biomacromolecules. Furthermore, we modify the surface of colloidal nanopores with organic moieties that can non-covalently interact with ions and molecules, and whose charge and shape respond to external stimuli, such as pH or light. As a result of the surface modification, we are able to control molecular transport through the colloidal nanopores, either by tuning the nature and strength of the non-covalent interactions or by changing the environmental conditions. Our research addresses fundamental problems of controlling molecular transport through nanoscale-sized artificial pores by their surface modification. Using colloidal crystals creates a new paradigm within the field of nanoporous materials because they (i) form through self-assembly, (ii) allow straightforward control of nanopore size in a broad range, (iii) possess exceptionally high molecular throughput, and (iv) offer a large variety of surface chemistries. Integrating nanoscale, functional organic molecules into the surface chemistry of colloidal materials will allow creating responsive nanoscale devices with a host of technological applications in drug delivery, separations and sensing.

Our work includes studying the mechanism of the colloidal membranes formation, preparing colloidal films on porous supports, investigating the role of defects in transport and controlling defect formation, improving mechanical strength of colloidal films and membranes, and preparing gold-coated colloidal materials. We develop and study the surface chemistry inside colloidal nanopores by introducing organic moieties onto the colloidal nanopore surface that can: (i) acquire charge by protonation/deprotonation, binding of ions, and oxidation; (ii) bind neutral molecules via non-covalent interactions; (iii) change conformation in response to temperature, pH, light, and binding. We study the transport of small molecules and biomacromolecules through unmodified and surface-modified colloidal membranes. By using films and membranes possessing well defined nanopores, we are able to quantitatively analyze the molecular transport rate as a function of pore size, surface modification and environmental conditions. These studies provide mechanistic insights and allow achieving a fine control of molecular transport through the nanopores.

As a result of our work with nanoporous colloidal systems we recently became involved in the preparation of novel hybrid proton-conducting nanoporous membranes based on surface-modified colloidal materials.

Schematic representation of a modular macromolecular

Figure 2. Schematic representation of a modular macromolecular antagonist incorporating integrin recognition functionality, fluorescent tag, and carboranyl moiety for Boron Neutron Capture.

In the third research area the overall objective is the development of modular macromolecular anti-cancer agents. Specifically, we are working on dendritic integrin antagonists. We are designing conjugates of synthetic integrin ligands with neutron capture functionality to allow highly selective targeting of the tumor neovasculature. Our modular approach, outlined in Figure 2, offers a high degree of structural flexibility and potential for rapid modification of each individual module. It simplifies the optimization of binding properties and bioavailability of the designed molecular antagonists without significant additional synthetic effort.

We are using monomeric avb3-selective integrin ligands as the targeting module and fluorescent dyes as the imaging module. At the moment we are focusing on the preparation of ester-baseddendrons carrying neutral, anionic and metal-coordinated carboranyl clusters. We plan to develop efficient convergent coupling strategies that will allow rapid conjugation of the designed dendritic modules into macromolecular agents. Synthesis of a macromolecular agent from the individual modules will require orthogonal protection of the functional groups to maximize yields of the desired product. In the future we will evaluate the affinity and specificity of the agents toward surface-immobilized integrins. Endothelial cell migration and proliferation assays will be used to evaluate the efficacy of the designed agents. Cellular localization/distribution will be evaluated by laser-scanning confocal microscopy. Functional testing of the pro-apoptotic activity of the macromolecular agents after neutron capture will be conducted at the Lujan Neutron Science Center at Los Alamos National Laboratory.

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