A Density Functional Tight Binding Layer for Deep Learning of Chemical Hamiltonians.

Current neural networks for predictions of molecular properties use quantum chemistry only as a source of training data. This paper explores models that use quantum chemistry as an integral part of the prediction process. This is done by implementing self-consistent-charge Density-Functional-Tight-Binding (DFTB) theory as a layer for use in deep learning models. The DFTB layer takes, as input, Hamiltonian matrix elements generated from earlier layers and produces, as output, electronic properties from self-consistent field solutions of the corresponding DFTB Hamiltonian. Backpropagation enables efficient training of the model to target electronic properties. Two types of input to the DFTB layer are explored, splines and feed-forward neural networks. Because overfitting can cause models trained on smaller molecules to perform poorly on larger molecules, regularizations are applied that penalize nonmonotonic behavior and deviation of the Hamiltonian matrix elements from those of the published DFTB model used to initialize the model. The approach is evaluated on 15 700 hydrocarbons by comparing the root-mean-square error in energy and dipole moment, on test molecules with eight heavy atoms, to the error from the initial DFTB model. When trained on molecules with up to seven heavy atoms, the spline model reduces the test error in energy by 60% and in dipole moments by 42%. The neural network model performs somewhat better, with error reductions of 67% and 59%, respectively. Training on molecules with up to four heavy atoms reduces performance, with both the spline and neural net models reducing the test error in energy by about 53% and in dipole by about 25%.

Spectral fine tuning of cyanine dyes: electron donor-acceptor substituted analogues of thiazole orange.

The introduction of electron donor and acceptor groups at strategic locations on a fluorogenic cyanine dye allows fine-tuning of the absorption and emission spectra while preserving the ability of the dye to bind to biomolecular hosts such as double-stranded DNA and a single-chain antibody fragment originally selected for binding to the parent unsubstituted dye, thiazole orange (TO). The observed spectral shifts are consistent with calculated HOMO-LUMO energy gaps and reflect electron density localization on the quinoline half of TO in the LUMO. A dye bearing donating methoxy and withdrawing trifluoromethyl groups on the benzothiazole and quinoline rings, respectively, shifts the absorption spectrum to sufficiently longer wavelengths to allow excitation at green wavelengths as opposed to the parent dye, which is optimally excited in the blue.

Computational and experimental characterization of a fluorescent dye for detection of potassium ion concentration.

The fluorescence of the SKC-513 ((E)-N-(9-(4-(1,4,7,10,13-pentaoxa-16-azacyclooctadecan-16-yl)phenyl)-6-(butyl(3-sulfopropyl)amino)-3H-xanthen-3-ylidene)-N-(3-sulfopropyl)butan-1-aminium) dye is shown experimentally to have high sensitivity to binding of the K(+) ion. Computations are used to explore the potential origins of this sensitivity and to make some suggestions regarding structural improvements. In the absence of K(+), excitation is to two nearly degenerate states, a neutral (N) excited state with a high oscillator strength, and a charge-transfer (CT) state with a lower oscillator strength. Binding of K(+) destabilizes the CT state, raising its energy far above the N state. The increase in fluorescence quantum yield upon binding of K(+) is attributed to the increased energy of the CT state suppressing a nonradiative pathway mediated by the CT state. The near degeneracy of the N and CT excited states can be understood by considering SKC-513 as a reduced symmetry version of a parent molecule with 3-fold symmetry. Computations show that acceptor-donor substituents can be used to alter the relative energies of the N and CT state, whereas a methylene spacer between the heterocycle and phenylene groups can be used to increase the coupling between these states. These modifications provide synthetic handles with which to optimize the dye for K(+) detection.