# Inorganic Chemistry Tools for Bioconjugation, Recognition and Imaging

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2023 · $249,954

## Abstract

Project Summary/Abstract
 Our laboratory is interested in developing new inorganic chemistry tools to address unmet needs in the
areas of bioconjugation, recognition, and imaging. In order to tackle these challenges, new molecular scaffolds
and biocompatible chemistry are crucial. The overall objective of this MIRA application is to further advance the
field of organomimetic boron cluster chemistry. Organomimetic features of these clusters arise from 1) their
ability to undergo facile functionalization chemistry with a wide array of substituents, forming stable covalent
bonds attached to the cluster¢s vertices and 2) unique 3D aromaticity, rendering these clusters amenable for
several modes of microscopy imaging. Within the scope of this work is also a set of new, rapid organometallic
transformations that were discovered during the original cycle of the MIRA funding that would allow one to
rationally tether boron clusters and other molecules under biologically relevant conditions.
 Our laboratory is interested in developing new transformations that mimic the operational simplicity with
which thiol ligands normally assemble onto a metallic gold surface. This chemistry has previously revolutionized
the ease with which we can create hybrid noble metal nanoparticles (e.g., thiol capped gold nanoparticles -
AuNPs). However, these hybrid AuNPs are not atomically precise, and the ligand corona is dynamic. These
features lead to hybrids with a non-uniform composition and size, ultimately limiting their applications for the
inhibition of protein-biomolecule interactions. Addressing this challenge, we have developed organometallic-
based methods for cluster modification, providing a covalently tethered dense corona of functional biomolecules
and ligands spatially arranged with three-dimensional precision. We propose to further expand this approach to
rapidly build up sophisticated atomically-precise 3D nanomolecules for multivalent binding to various biological
targets, including virus entry receptors, biological membranes, and cellular growth factors. We also propose to
utilize the inherent robustness and reaction kinetics associated with the developed Au-based reagents for
biomolecular positron-emission tomography (PET) labeling. We have also been engaged in the development of
new boron cluster chemistry, allowing for the positioning of multiple reactive functional groups on a three-
dimensional cluster and use these rigid 3D species to label and tether biomolecules to achieve unconventional
folding and recognition. We propose chemistry that will enable the labeling of small molecules, peptides, proteins,
and cells with various boron cluster scaffolds, which can subsequently be used as multivalent binders, affinity
tags, and fluorescent-free labels using Raman microscopy imaging. Lastly, we propose the use of
perfunctionalized boron clusters as dual staining/fluorophore agents for correlative light and electron microscopy
(CLEM). Specifically, we will wo...

## Key facts

- **NIH application ID:** 10797628
- **Project number:** 3R35GM124746-07S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Alexander Michael Spokoyny
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $249,954
- **Award type:** 3
- **Project period:** 2017-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10797628

## Citation

> US National Institutes of Health, RePORTER application 10797628, Inorganic Chemistry Tools for Bioconjugation, Recognition and Imaging (3R35GM124746-07S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10797628. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*