Photochemical Fingerprinting Is a Sensitive Probe for the Detection of Synthetic Cannabinoid Receptor Agonists; toward Robust Point-of-Care Detection.

With synthetic cannabinoid receptor agonist (SCRA) use still prevalent across Europe and structurally advanced generations emerging, it is imperative that drug detection methods advance in parallel. SCRAs are a chemically diverse and evolving group, which makes rapid detection challenging. We have previously shown that fluorescence spectral fingerprinting (FSF) has the potential to provide rapid assessment of SCRA presence directly from street material with minimal processing and in saliva. Enhancing the sensitivity and discriminatory ability of this approach has high potential to accelerate the delivery of a point-of-care technology that can be used confidently by a range of stakeholders, from medical to prison staff. We demonstrate that a range of structurally distinct SCRAs are photochemically active and give rise to distinct FSFs after irradiation. To explore this in detail, we have synthesized a model series of compounds which mimic specific structural features of AM-694. Our data show that FSFs are sensitive to chemically conservative changes, with evidence that this relates to shifts in the electronic structure and cross-conjugation. Crucially, we find that the photochemical degradation rate is sensitive to individual structures and gives rise to a specific major product, the mechanism and identification of which we elucidate through density-functional theory (DFT) and time-dependent DFT. We test the potential of our hybrid "photochemical fingerprinting" approach to discriminate SCRAs by demonstrating SCRA detection from a simulated smoking apparatus in saliva. Our study shows the potential of tracking photochemical reactivity via FSFs for enhanced discrimination of SCRAs, with successful integration into a portable device.

Biotin-tagged fluorescent sensor to visualize 'mobile' Zn2+ in cancer cells.

A cancer cell-targeting fluorescent sensor has been developed to image mobile Zn2+ by introducing a biotin group. It shows a highly selective response to Zn2+in vitro, no toxicity in cellulo and images 'mobile' Zn2+ specifically in cancer cells. We believe this probe has the potential to help improve our understanding of the role of Zn2+ in the processes of cancer initiation and development.

Photo-stability of peptide-bond aggregates: N-methylformamide dimers.

The formation of weakly-bound dimers of N-methylformamide (NMF) and the photochemistry of these dimers after irradiation at 248 nm were explored using matrix-isolation spectroscopy. Calculations were used to characterize the diverse isomers and assign their IR spectra; non-adiabatic dynamics was simulated to understand their photo-deactivation mechanism. The most stable dimers, and , were obtained by trans-trans aggregation (N-HO[double bond, length as m-dash]C interactions) and could be identified in the matrix. The main products formed after irradiation are the trans-cis dimers ( and ), also stabilized by N-HO[double bond, length as m-dash]C interactions. In contrast to the photochemistry of the monomers, no dissociative products were observed after 248 nm irradiation of the dimers. The absence of dissociative products can be explained by a proton-transfer mechanism in the excited state that is faster than the photo-dissociative mechanism. The fact that hydrogen bonding has such a significant effect on the photochemical stability of NMF has important implications to understand the stability of peptide-bonded systems to UV irradiation.

CNDOL: A fast and reliable method for the calculation of electronic properties of very large systems. Applications to retinal binding pocket in rhodopsin and gas phase porphine.

Very large molecular systems can be calculated with the so called CNDOL approximate Hamiltonians that have been developed by avoiding oversimplifications and only using a priori parameters and formulas from the simpler NDO methods. A new diagonal monoelectronic term named CNDOL/21 shows great consistency and easier SCF convergence when used together with an appropriate function for charge repulsion energies that is derived from traditional formulas. It is possible to obtain a priori molecular orbitals and electron excitation properties after the configuration interaction of single excited determinants with reliability, maintaining interpretative possibilities even being a simplified Hamiltonian. Tests with some unequivocal gas phase maxima of simple molecules (benzene, furfural, acetaldehyde, hexyl alcohol, methyl amine, 2,5 dimethyl 2,4 hexadiene, and ethyl sulfide) ratify the general quality of this approach in comparison with other methods. The calculation of large systems as porphine in gas phase and a model of the complete retinal binding pocket in rhodopsin with 622 basis functions on 280 atoms at the quantum mechanical level show reliability leading to a resulting first allowed transition in 483 nm, very similar to the known experimental value of 500 nm of "dark state." In this very important case, our model gives a central role in this excitation to a charge transfer from the neighboring Glu(-) counterion to the retinaldehyde polyene chain. Tests with gas phase maxima of some important molecules corroborate the reliability of CNDOL/2 Hamiltonians.