jp2c07783_si_001.pdf (2.18 MB)
Computational Investigations into Two-Photon Fibril Imaging Using the DANIR-2c Probe
journal contributionposted on 2023-04-04, 20:29 authored by N. Arul Murugan, Robert Zaleśny
The design of novel fibril imaging molecules for medical diagnosis requires the simultaneous optimization of fibril-specific optical properties and binding specificity toward amyloid fibrils. Because of the possibility to monitor internal organs and deep tissues, the two-photon probes that can absorb in the infrared (IR) and near-IR (NIR) region with a significant two-photon absorption cross section are of immense interest. To contribute to this exploration of chemical compounds suitable for two-photon fibril imaging, we have computationally studied the one- and two-photon properties of a donor–acceptor-substituted DANIR-2c probe, which was used for in vivo detection of β-amyloid deposits using fluorescence spectroscopy. In particular, a multiscale computational approach was employed involving molecular docking, molecular dynamics, hybrid QM/MM molecular dynamics, and coupled-cluster/MM to study the binding of the studied probe to amyloid fibril and its one- and two-photon absorption properties in the fibrillar environment. Multiple binding sites are available for this probe in amyloid fibril, and the one corresponding to the largest binding affinity exhibits also the largest and experimentally meaningful two-photon absorption cross section, thus demonstrating the potential of the studied probe in two-photon microscopy.
monitor internal organsmedical diagnosis requiresdonor – acceptorchemical compounds suitablespecific optical propertiesmultiscale computational approachphoton absorption propertiesmultiple binding sitesexperimentally meaningful twophoton fibril imagingmm molecular dynamicsphoton propertiesmolecular dynamicscomputational investigationsphoton probesphoton microscopyvivo detectionthus demonstratingsimultaneous optimizationsignificant twoimmense interesthybrid qmfibrillar environmentdeep tissuescomputationally studiedamyloid fibril