Short hydrogen bonds enhance nonaromatic protein-related fluorescence.

Fluorescence in biological systems is usually associated with the presence of aromatic groups. Here, by employing a combined experimental and computational approach, we show that specific hydrogen bond networks can significantly affect fluorescence. In particular, we reveal that the single amino acid L-glutamine, by undergoing a chemical transformation leading to the formation of a short hydrogen bond, displays optical properties that are significantly enhanced compared with L-glutamine itself. Ab initio molecular dynamics simulations highlight that these short hydrogen bonds prevent the appearance of a conical intersection between the excited and the ground states and thereby significantly decrease nonradiative transition probabilities. Our findings open the door to the design of new photoactive materials with biophotonic applications.

Fluorescence Quantum Yields in Complex Environments from QM-MM TDDFT Simulations: The Case of Indole in Different Solvents.

Fluorescence is commonly exploited to probe microscopic properties. An important example is tryptophan in protein environments, where variations in fluorescence quantum yield, and in absorption and emission maxima, are used as indicators of changes in the environment. Modeling the fluorescence quantum yield requires the determination of both radiative and nonradiative decay constants, both on the potential energy surface of the excited fluorophore. Furthermore, the inclusion of complex environments implies their accurate representation as well as extensive configurational sampling. In this work, we present and test various methodologies based on time-dependent density functional theory (TDDFT) and quantum mechanics/molecular mechanics (QM/MM) dynamics that take all of these requirements into account to provide a quantitative prediction of the effect of the environment on the fluorescence quantum yield of indole, a tryptophan fluorophore. This investigation paves the way for applications to the realistic spectroscopic characterization of the local protein environment of tryptophan from computer simulations.

Exploring the Mechanisms behind Non-aromatic Fluorescence with the Density Functional Tight Binding Method.

Recent experimental findings reveal nonconventional fluorescence emission in biological systems devoid of conjugated bonds or aromatic compounds, termed non-aromatic fluorescence (NAF). This phenomenon is exclusive to aggregated or solid states and remains absent in monomeric solutions. Previous studies focused on small model systems in vacuum show that the carbonyl stretching mode along with strong interaction of short hydrogen bonds (SHBs) remains the primary vibrational mode explaining NAF in these systems. In order to simulate larger model systems taking into account the effects of the surrounding environment, in this work we propose using the density functional tight-binding (DFTB) method in combination with non-adiabatic molecular dynamics (NAMD) and the mixed quantum/molecular mechanics (QM/MM) approach. We investigate the mechanism behind NAF in the crystal structure of l-pyroglutamine-ammonium, comparing it with the related nonfluorescent amino acid l-glutamine. Our results extend our previous findings to more realistic systems, demonstrating the efficiency and robustness of the proposed DFTB method in the context of NAMD in biological systems. Furthermore, due to its inherent low computational cost, this method allows for a better sampling of the nonradiative events at the conical intersection which is crucial for a complete understanding of this phenomenon. Beyond contributing to the ongoing exploration of NAF, this work paves the way for future application of this method in more complex biological systems such as amyloid aggregates, biomaterials, and non-aromatic proteins.

Non-Aromatic Fluorescence in Biological Matter: The Exception or the Rule?

While in the vast majority of cases fluorescence in biological matter has been attributed to aromatic or conjugated groups, peptides associated with neurodegenerative diseases, such as Alzheimer's, Parkinson's, or Huntington's, have been recently shown to display an intrinsic visible fluorescence even in the absence of aromatic residues. This has called the attention of researchers from many different fields, trying to understand the origin of this peculiar behavior and, at the same time, motivating the search for novel strategies to control the optical properties of new biophotonic materials. Today, after nearly 15 years of its discovery, there is a growing consensus about the mechanism underlying this phenomenon, namely, that electronic interactions between non-optically active molecules can result in supramolecular assemblies that are fluorescent. Despite this progress, many aspects of this phenomenon remain uncharted territory. In this Perspective, we lay down the state-of-the-art in the field highlighting the open questions from both experimental and theoretical fronts in this fascinating emerging area of non-aromatic fluorescence.