Chiral Ligand-Protected Gold Nanoclusters as Biosensors for Small Chiral Biomolecules: A Computational Study

TL;DR

This study explores using chiral gold nanoclusters as noninvasive sensors for small chiral biomolecules, validated through simulations and calculations.

Contribution

A novel strategy for noninvasive chiral sensing using ligand-protected gold nanoclusters, validated computationally.

Findings

Binding probabilities of chiral biomolecules to nanoclusters varied widely, from <1% to 100%.

Electrostatic interactions dominated, with hydrogen bonding and van der Waals effects also playing roles.

Circular dichroism spectra predicted enantiomer-specific adsorption, enabling experimentally realizable sensing.

Abstract

Detection of chiral
biomolecules in biological environments presents
an important challenge: to develop sensitive, noninvasive sensors
that Could have an impact in several areas such as drug discovery,
diagnostics of diseases, and care. In this work, we introduce a strategy
for experimentally realizable, noninvasive sensing of small chiral
biomolecules in aqueous solvents, validated via classical force-field
molecular dynamics simulations and density functional theory calculations.
We investigated the interactions of the L/D forms of glutathione and
seven chiral amino acids (Ala, Arg, Asp, Cys, Glu, Ser, Tyr) with
six chiral, water-soluble, thiolate-protected gold nanoclusters in
the range of 25–144 gold atoms, via dynamical sampling extending
up to 3 μs time scales in water at neutral pH. We found surprisingly
large variations in the binding probability (from <1% to 100%)
of these analytes to the nanoclusters, with the dominating interaction
being electrostatics between the analyte and the nanoclusters’
ligand surface, augmented by hydrogen bonding and van der Waals interactions.
Computed circular dichroism spectra for several nanocluster–analyte
complexes predict the identification of analyte-specific adsorption
events and even the resolution of the adsorbed enantiomer in selected
cases, constituting an experimentally realizable sensing function.
Our results suggest that chiral ligand-protected gold nanoclusters
could be used for noninvasive chiral sensing, creating a tunable toolbox
where the nanocluster size and chiral ligand type could be varied
for optimizing the sensing activity for specific targets.

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