Development of a ratiometric fluorescent zinc ion probe in near-infrared region, based on tricarbocyanine chromophore

Novel ratiometric fluorescent probes for Zn2+ in the near-infrared region, based on a tricarbocyanine chromophore, have been designed, synthesized, and evaluated. Upon addition of Zn2+, a 44 nm red shift of the absorption maximum was observed, which indicates that this probe could work as a ratiometric probe for Zn2+. This change is due to the difference in the electron-donating ability of the amine substituent before and after reaction with Zn2+. This fluorescence modulation of amine-substituted tricarbocyanines should be applicable to dual-wavelength measurement of various biomolecules or enzyme activities.     

Spectral deep learning for prediction and prospective validation of functional groups

State-of-the-art identification of the functional groups present in an unknown chemical entity requires the expertise of a skilled spectroscopist to analyse and interpret Fourier transform infra-red (FTIR), mass spectroscopy (MS) and/or nuclear magnetic resonance (NMR) data. This process can be time-consuming and error-prone, especially for complex chemical entities that are poorly characterised in the literature, or inefficient to use with synthetic robots producing molecules at an accelerated rate. Herein, we introduce a fast, multi-label deep neural network for accurately identifying all the functional groups of unknown compounds using a combination of FTIR and MS spectra. We do not use any database, pre-established rules, procedures, or peak-matching methods. Our trained neural network reveals patterns typically used by human chemists to identify standard groups. Finally, we experimentally validated our neural network, trained on single compounds, to predict functional groups in compound mixtures. Our methodology showcases practical utility for future use in autonomous analytical detection.

A new multi-label deep neural network architecture is used to combine Infrared and mass spectra, trained on single compounds to predict functional groups, and experimentally validated on complex mixtures.     

Spectral characterization of a novel near-infrared cyanine dye: a study of its complexation with metal ions

The spectral features of the near-infrared (NIR) dye TG-170 in different solutions and its complexation with several metal ions were investigated. The absorbance maxima of the dye are at λ=819, 805, and 791 nm in dimethyl sulfoxide (DMSO), methanol, and a buffer of pH 5.9, respectively. These values match the output of a commercially available laser diode (780 nm), thus making use of such a source practical for excitation. The emission wavelengths of the dye are at λ_em =822, 812, and 803 nm in DMSO, methanol, and the buffer, respectively. The molar absorptivity and fluorescence quantum yield increase accordingly. The addition of either an Al(III) ion or Be(II) ion resulted in fluorescence quenching of the dye. The Stern–Volmer quenching constant, K_SV, was calculated from the Stern–Volmer plot to be K_SV=3.11×10⁵ M⁻¹ for the Al(III) ion and K_SV=1.17×10⁶ M⁻¹ for the Be(II) ion. The molar ratio of the metal to the dye was established to be 1:1 for both metal ions. The stability constant, K_S, of the metal–dye complex was calculated to be 4.37×10⁴ M⁻¹ for the Al–dye complex and 1.94×10⁶ M⁻¹ for the Be–dye complex.     

On the chromophore of polyacrylonitrile

Further evidence is presented to show that the chromophore of polyacrylonitrile is formed by polymerization of the nitrile groups, rather than by dehydrogenation of the polymer backbone. The polyimine structure formed is resistant to hydrolysis; hence, the nitrogen content of hydrolyzed polymer increases with increased chromophore formation.     

A cyanine based fluorophore emitting both single photon near-infrared fluorescence and two-photon deep red fluorescence in aqueous solution

Optical imaging provides an indispensable way to locate tumors in their early stages with high sensitivity and signal to background ratio. A heptamethine cyanine based fluorophore that emits both single photon near-infrared fluorescence and two-photon deep red fluorescence under physiological conditions was developed. Linear and nonlinear photophysical properties of this fluorophore were investigated and it demonstrated the capability to label lysosomes in cancer cells. The advantages of this fluorophore, including tolerable cytotoxicity, high fluorescence quantum yield, and the ability to emit both near-infrared single photon fluorescence and deep red two photon fluorescence in aqueous solution, give it potential to be used in intra-operatively optical image-guided tumor excision followed by two-photon fluorescence microscopy biopsy analysis after a single administration.     

Synthesis of the chromophore of rubrolone

A synthesis of 2, the chromophore of nibrolone (1), is described. The key constructive step is the regiospecific cycloaddition 10 + 11a → 12a.     

Synthesis of analogues of calicheamicin and neocarzinostatin chromophore

The work presents a synthetic route to the CD ring of calicheamicin and in the case of neocarzinostatin an approach to a functionalised cyclopentane-1,3-diol containing the naturally occurring naphthoate and a glucosamine motif. In the case of the NCS derivative some biological activity (cytotoxicity) was observed.     

Negative photochromism of a TCF chromophore

A novel negative photochromic compound has been designed and synthesized. The structure of the compound consists of a tricyanofuran (TCF) moiety and a quinoline moiety, bridged by a double bond. Upon irradiation with visible light, the neutral thermostable form of the compound quickly transforms to a cyclic zwitterionic form with over 90% conversion efficiency.     

Formal total synthesis of neocarzinostatin chromophore

[reaction: see text] An efficient route to the neocarzinostatin chromophore aglycon has been developed. The present strategy involves a stereoselective intramolecular acetylide-aldehyde cyclization to form the C5-C6 bond, followed by efficient installation of alpha-epoxide, naphthoate, and carbonate functionalities. The C8-C9-olefin was introduced by using the Martin sulfurane dehydration reaction to furnish the highly reactive aglycon.     

Synthesis and photochemistry of pH-sensitive GFP chromophore analogs

GFP chromophore analogs (7a-e, 8, and 10a,b) containing 2-thienyl-, 5-methyl-2-furyl-, 2-pyrryl, and 6-methyl-2-pyridyl-groups were synthesized and their fluorescence spectra recorded in the pH range 1-7. NMR studies showed that protonation of 8 (2-thienyl system) inhibited photoisomerization (Z-E) about the exocyclic double bond but that protonation of 7c (E + Z) (2-pyrryl system) gave only 7cE. Fluorescence studies revealed enhancement of fluorescence intensity of 7c and 7b,e (furyl system) below pH 2.5 and gave a similar result for 10a (pyridyl system) below pH 6. Quantum yields at pH 1 were low, probably due to excited state proton transfer (ESPT).     

Radical compounds and metal complexes with azobenzene chromophore

Series of organic radical compounds with trans-azobenzene chromophore have been prepared to see the photo-induced isomerizations to the corresponding cis-azobenzenes and the possible changes of intermolecular magnetic interactions based on the isomerizations. Although the cis-isomers with p-nitro- or p-dimethylamino-substituent on one side and TEMPO-attached long alkoxy group on the other side could not be isolated as stable solids, the cis-isomers of unsubstituted derivatives at 4-position and with a TEMPO group at 4′-position have successfully been isolated as relatively stable solid materials showing apparent changes of intermolecular magnetic interactions. A couple of Mn(hfac)₂ complexes derived from isomeric TEMPO-substituted esters were found to be reluctant to the photo-isomerization upon irradiation.     

Spectral bandshape and intensity of the C-H chromophore in the infrared spectra of CF3H and C4F9H

The vapour phase IR spectra and integrated band intensities of the fundamental and first-overtone transition of the C-H chromophore in CF₃H and (CF₃)₃CH are reported. The vibrational coarse bandshapes for (CF₃)₃CH are consistent with lorentzians of width Γ = 3 cm^?1 (fundamental) and Γ = 12 cm^?1 (overtone). The results are discussed in connection with time-dependent molecular processes and IR photochemistry.     

Ultrafast vibrational spectroscopy of the flavin chromophore

Ultrafast time-resolved infrared (TRIR) spectra of flavin adenine dinucleotide (FAD) and the anion of lumiflavin (Lf-) are described. Ground-state recovery and excited-state decay of FAD reveal a common dominant ultrafast relaxation and a minor slower component. The Lf- transient lacks a fast component. No intermediate species are observed, suggesting that the quenching mechanism is internal conversion promoted by interaction of the adenine and isoalloxazine rings in FAD. Modes are assigned, and the potential for extension of the TRIR method to photoactive proteins is discussed.     

Deactivation mechanism of the green fluorescent chromophore

We report time-resolved fluorescence data for the anion of p-hydroxybenzylidene dimethylimidazolinone (p-HBDI), a model chromophore of the green fluorescence protein, in viscous glycerol-water mixtures over a range of temperatures, T. The markedly nonexponential decay of the excited electronic state is interpreted with the aid of an inhomogeneous model possessing a Gaussian coordinate-dependent sink term. A nonlinear least-squares fitting routine enables us to achieve quantitative fits by adjusting a single activation parameter, which is found to depend linearly on 1/T. We derive an analytic expression for the absolute quantum yield, which is compared with the integrated steady-state fluorescence spectra. The microscopic origins of the model are discussed in terms of two-dimensional dynamics, coupling the phenyl-ring rotation to a swinging mode that brings this flexible molecule to the proximity of a conical intersection on its multidimensional potential energy surface.     

Synthesis of spiropyrans containing an additional chromophore

Spiropyrans of the phenanthridine and indoline series containing phenylazo or benzoylgroups as substituents in the chromene ring were synthesized. These substituents facilitate the formation of deeply colored merocyanine forms in polar solvents. The presence of a phenylazo group causes the intense color of the cyclic forms of the spiropyrans.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1618–1623, December, 1973.     

Oxazolo analogs of the actinomycin D chromophore

Condensation of a tricyclic phenoxazin-2-amino-3-one (a model for the actinomycin D ring system) with acetaldehyde or benzaldehyde or with pyruvic acid as an acetaldehyde precursor gave tetracyclic 5H-oxazolo[4,5-b]phenoxazines. The pyruvic acid reaction proceeds efficiently in one step. The latter compounds were oxidized in a novel reaction by 2,3-dichloro-5,6-dicyano-benzoquinone exclusively at position 8 in the benzenoid ring. Uv, ir, nmr, and mass spectrometric data are reported.     

Modeling photoabsorption of the asFP595 chromophore

The fluorescent protein asFP595 is a promising photoswitchable biomarker for studying processes in living cells. We present the results of a high level theoretical study of photoabsorption properties of the model asFP595 chromophore molecule in biologically relevant protonation states: anionic, zwitterionic, and neutral. Ground state equilibrium geometry parameters are optimized in the PBE0/(aug)-cc-pVDZ density functional theory approximation. An augmented version of multiconfigurational quasidegenerate perturbation theory (aug-MCQDPT2) following the state-averaged CASSCF/(aug)-cc-pVDZ calculations is used to estimate the vertical S0-S1 excitation energies for all chromophore species. An accuracy of this approach is validated by comparing the computed estimates of the S0-S1 absorption maximum of the closely related chromophore from the DsRed protein to the known experimental value in the gas phase. An influence of the CASSCF active space on the aug-MCQDPT2 excitation energies is analyzed. The zwitterionic form of the asFP595 chromophore is found to be the most sensitive to a particular choice and amount of active orbitals. This observation is explained by the charge-transfer type of the S0-S1 transition involving the entire conjugated pi-electron system for the zwitterionic protonation state. According to the calculation results, the anionic form in the trans conformation is found to possess the most red-shifted absorption band with the maximum located at 543 nm. The bands of the zwitterionic and neutral forms are considerably blue-shifted compared to those of the anionic form. These conclusions are at variance with the results obtained in the TDDFT approximation for the asFP595 chromophore. The absorption wavelengths computed in the aug-MCQDPT2/CASSCF theory are as follows: 543 (535), 470 (476), and 415 (417) nm for the anionic, zwitterionic, and neutral forms of the trans and cis (in parentheses) isomers of the asFP595 chromophore. These data can be used as a reference for further theoretical studies of the asFP595 chromophore in different media and for modeling photoabsorption properties of the asFP595 fluorescent protein.     

The molecular topography of phytochrome: chromophore and apoprotein

Phytochrome serves as the photochromic receptor for a number of morphogenic and developmental responses to red light in higher plants. The photoreversible phototransformation of 124 kDa oat phytochrome involves several structural changes in the chromophore and the apoprotein, including a configurational/conformational isomerization and secondary/tertiary structural changes respectively. For example, there appears to be a specific interaction between the chromophore and the amino terminus segment in the Pfr form of phytochrome, which results in a photoreversible peptide folding of the amino terminus peptide chain. Other structural changes also accompany the phototransformation, as has been probed by peptide mapping, phosphorylation, and monoclonal antibodies.     

Efficient construction of the kedarcidin chromophore ansamacrolide

[Structure: see text] The streamlined assembly of the ansamacrolide framework of the kedarcidin chromophore via an efficient atropselective Sonogashira coupling step is described. To this end, two newly improved practical syntheses of the cyclopentene and diyne fragments have been developed, which feature 0.2 mol % catalytic loadings for an RCM step and i-PrMgCl/CH2I2 as a new entry to gem-disubstituted epoxides from ketones, both being applicable to 49-g scales.