Heavy Halogen Atoms Research Articles

The heavy-atom effect on xanthene dyes for photopolymerization by visible light

Heavy halogen atoms on the xanthene ring significantly increase the photoredox catalytic performance for visible-light-induced photopolymerization.

Quadrupole Correction: From Molecular Electrostatic Potential to Free Energies of Halogen Bonding.

Recently several molecular mechanics models of halogen bonding have been published. They describe the electrostatic potential anisotropy near the heavy halogen atom (known as a σ-hole) in different ways, ranging from an all-atom multipole expansion to a single positive extra-point charge. However, the question of a reasonable balance between the accuracy and the simplicity of the model remains open. In this work, we introduce the simplistic RESPQ electrostatics model built on the RESP charges complemented with fixed atomic quadrupoles. We show that it: (1) correctly describes the MEP anisotropy of aromatic halogen atoms, (2) improves the description of the halogen-water interaction energies in both halogen and hydrogen bonding cases, (3) provides an excellent estimation of solvation free energy differences of aromatic halogens, and (4) is compatible (with the help of multipole charge cluster approximation) with contemporary molecular modeling packages.

Ethanothermal synthesis of phenol-derived carbon dots with multiple color emission via a versatile oxidation strategy

Herein, we report an ethanothermal synthesis of multicolor fluorescent carbon dots (CDs) by using a series of phenols and oxidants as the precursors. The emission colors of CDs are well-controlled at blue, green, yellow or red wavelengths by adjusting the combination of a phenol and an oxidant. And the naphthalenediol with highly reactivity and the oxidant with heavy halogen atom result in CDs exhibiting long wavelength emission. The resulting nanodots are characterized as amorphous aggregates with abundant oxygen species. The phenol-derived CDs can be used as highly processible fillers to fabricate epoxy composites, and a white light-emitting diode (LED) employing the multicolor CDs/epoxy composite as the light converter is also demonstrated.

Halide‐Substituted Phosphacyclohexadienyl Iron Complexes: Covalent Structures vs. Ion Pairs

The coordination chemistry of phosphinines (phosphabenzenes) has been intensively investigated over the last decades, but metal complexes of halophosphinines and related halide‐substituted phosphacyclohexadienyls have remained scarce. Here, we describe the synthesis of a series of complexes [Cp*Fe(1‐F‐PC5Ph3H2)] (2‐F, Cp* = C5Me5), [Cp*Fe(1‐Cl‐PC5Ph3H2)] (2‐Cl), [Cp*Fe(PC5Ph3H2)]Br (2‐Br) and [Cp*Fe(PC5Ph3H2)]I (2‐I), which were obtained by reacting the previously reported 2,4,6‐triphenylphosphinine iron complex [K([18]crown‐6)(thf)2] [Cp*Fe(PC5Ph3H2)] (1) with electrophilic halogenating agents. To the best of our knowledge, 2‐F and 2‐Cl are the first π‐coordinated λ3‐halophosphacyclohexadienyl complexes with covalent P–X bonds (X = halogen). In the solid state 2‐Br and 2‐I show ionic structures with [Cp*Fe(PC5Ph3H2)]+ cations and separated X– anions. Anion exchange of I– in 2‐I for [BArF4]– {ArF = 3,5‐(CF3)2C6H3} affords [Cp*Fe(PC5Ph3H2)][BArF4] (2‐[BArF4]), which also displays an ionic structure. These new complexes were further characterized by solid‐state and solution 31P NMR spectroscopy, UV/Vis spectroscopy, elemental analyses, electrical conductivity measurements in solution, and DFT calculations. The resulting data indicate that 2‐F retains its covalent P–F bond in THF, fluorobenzene, and acetonitrile solution, while the remaining 2‐X complexes containing heavier halogen atoms (X = Cl, Br, and I) apparently form ion pairs in such solvents.

The effects of halogen elements on the opening of an icosahedral B12 framework.

The fully halogenated or hydrogenated B12X122- (X = H, F, Cl, Br and I) clusters are confirmed to be icosahedral. On the other hand, the bare B12 cluster is shown to have a planar structure. A previous study showed that a transformation from an icosahedron to a plane happens when 5 to 7 iodine atoms are remained [P. Farràs et al., Chem. - Eur. J. 18, 13208-13212 (2012)]. Later, the transition was confirmed to be seven iodine atoms based on an infrared spectroscopy study [M. R. Fagiania et al., Chem. Phys. Lett. 625, 48-52 (2015)]. In this study, we investigated the effects of different halogen atoms on the opening of the B12 icosahedral cage by means of density functional theory calculations. We found that the halogen elements do not have significant effects on the geometries of the clusters. The computed infrared (IR) spectra show similar representative peaks for all halogen doped clusters. Interestingly, we found a blue-shift in the IR spectra with the increase in the mass of the halogen atoms. Further, we compared the Gibbs free energies at different temperatures for different halogen atoms. The results show that the Gibbs free energy differences between open and close structures of B12X7- become larger when heavier halogen atoms are presented. This interesting finding was subsequently investigated by the energy decomposition analysis.

Synthesis and Cytotoxicity of Arene‐Ru Compounds Containing 4‐Nitroaniline or 2‐Halogenated 4‐Nitroaniline

The compounds [(η6‐p‐cymene)RuCl2(4‐nitroaniline)] and [(η6‐p‐cymene)RuCl2(2‐halogen‐4‐nitroaniline)] were synthesized and characterized by various means. The [(η6‐p‐cymene)RuCl2(4‐nitroaniline)] and [(η6‐p‐cymene)RuCl2(2‐fluoro‐4‐nitroaniline)] compounds were determined by X‐ray diffraction, appearing in a distorted piano‐stool type of arrangement with similar bond lengths and angles around the ruthenium. The compounds exhibited moderate to strong in vitro cytotoxicity against A549 and MCF‐7 human cancer cells. Substitution of heavy halogen atom on the ortho position of para‐nitroaniline weakened the cytotoxicity against both of MCF‐7 and A549, except the cases of fluorine substitution for hydrogen atom regarding A549 and bromine substitution for chlorine atom regarding MCF‐7, which showed minor deviation.

Repositioning organohalogen drugs: a case study for identification of potent B-Raf V600E inhibitors via docking and bioassay.

Drug repositioning has been attracting increasingly attention for its advantages of reducing costs and risks. Statistics showed that around one quarter of the marketed drugs are organohalogens. However, no study has been reported, to the best of our knowledge, to aim at efficiently repositioning organohalogen drugs, which may be attributed to the lack of accurate halogen bonding scoring function. Here, we present a study to show that two organohalogen drugs were successfully repositioned as potent B-Raf V600E inhibitors via molecular docking with halogen bonding scoring function, namely D3DOCKxb developed in our lab, and bioassay. After virtual screening by D3DOCKxb against the database CMC (Comprehensive Medicinal Chemistry), 3 organohalogen drugs that were predicted to form strong halogen bonding with B-Raf V600E were purchased and tested with ELISA-based assay. In the end, 2 of them, rafoxanide and closantel, were identified as potent inhibitors with IC50 values of 0.07 μM and 1.90 μM, respectively, which are comparable to that of vemurafenib (IC50: 0.17 μM), a marketed drug targeting B-Raf V600E. Single point mutagenesis experiments confirmed the conformations predicted by D3DOCKxb. And comparison experiment revealed that halogen bonding scoring function is essential for repositioning those drugs with heavy halogen atoms in their molecular structures.

New small molecule inhibitors of histone methyl transferase DOT1L with a nitrile as a non-traditional replacement for heavy halogen atoms

A number of new nucleoside derivatives are disclosed as inhibitors of DOT1L activity. SARs established that DOT1L inhibition could be achieved through incorporation of polar groups and small heterocycles at the 5-position (5, 6, 12) or by the application of alternative nitrogenous bases (18). Based on these results, CN-SAH (19) was identified as a potent and selective inhibitor of DOT1L activity where the polar 5-nitrile group was shown by crystallography to bind in the hydrophobic pocket of DOT1L. In addition, we show that a polar nitrile group can be used as a non-traditional replacement for heavy halogen atoms.

Prediction of silicon-based room temperature quantum spin Hall insulator via orbital mixing

The search for realistic materials capable of supporting the room temperature quantum spin Hall (QSH) effect remains a challenge, especially when compatibility with the current electronics industry is required. We report a theoretical prediction to identify halogenated silicon films as excellent candidates, which demonstrate high stability, flexibility, and tunable spin-orbit coupling (SOC) gaps up to ∼0.5 eV under minimal strain below 3%. The extraordinary SOC strength is mainly contributed by the p-orbital of heavy halogen atoms hybridized with the px,y-orbitals of Si scaffold, and thus can be easily manipulated by strain (being ∼100 times more effective than in silicene) or substrate. Not only the instability problem of silicene for real applications is solved, but also it provides a new strategy to drastically enhance SOC of light-element scaffolds by orbital hybridization. The silicon-based QSH insulator is most promising for developing next-generation, low-power consumption nanoelectronics and spintronics at ambient conditions.

Intermolecular Electronic Coupling of Organic Units for Efficient Persistent Room-Temperature Phosphorescence.

Although persistent room‐temperature phosphorescence (RTP) emission has been observed for a few pure crystalline organic molecules, there is no consistent mechanism and no universal design strategy for organic persistent RTP (pRTP) materials. A new mechanism for pRTP is presented, based on combining the advantages of different excited‐state configurations in coupled intermolecular units, which may be applicable to a wide range of organic molecules. By following this mechanism, we have developed a successful design strategy to obtain bright pRTP by utilizing a heavy halogen atom to further increase the intersystem crossing rate of the coupled units. RTP with a remarkably long lifetime of 0.28 s and a very high quantum efficiency of 5 % was thus obtained under ambient conditions. This strategy represents an important step in the understanding of organic pRTP emission.

Four-Component Relativistic DFT Calculations of (13)C Chemical Shifts of Halogenated Natural Substances.

We have calculated the (13)C NMR chemical shifts of a large ensemble of halogenated organic molecules (81 molecules for a total of 250 experimental (13)C NMR data at four different levels of theory), ranging from small rigid organic compounds, used to benchmark the performance of various levels of theory, to natural substances of marine origin with conformational degrees of freedom. Carbon atoms bonded to heavy halogen atoms, particularly bromine and iodine, are known to be rather challenging when it comes to the prediction of their chemical shifts by quantum methods, due to relativistic effects. In this paper, we have applied the state-of-the-art four-component relativistic density functional theory for the prediction of such NMR properties and compared the performance with two-component and nonrelativistic methods. Our results highlight the necessity to include relativistic corrections within a four-component description for the most accurate prediction of the NMR properties of halogenated organic substances.

Abnormal synergistic effects between Lewis acid–base interaction and halogen bond in F3B···NCX···NCM

An abnormal synergistic effect was found between the Lewis acid–base interaction and halogen bond in triads F3B···NCX···NCM (X and M are halogen atoms), where the strong Lewis acid–base interaction between F3B and NCX has a larger enhancement than the weak halogen bond between NCX and NCM. This is in contrast with the traditional cooperative effect. It is interesting that the alkali-metal substituent as well as the heavier halogen atom play a more remarkable role in the enhancement of the interaction F3B···NCX than that of NCX···NCM, particularly, the alkali-metal substituent makes the abnormal synergistic effect be the traditional cooperative one.

Dual Functioning Thieno-Pyrrole Fused BODIPY Dyes for NIR Optical Imaging and Photodynamic Therapy: Singlet Oxygen Generation without Heavy Halogen Atom Assistance.

We discovered a rare phenomenon wherein a thieno-pyrrole fused BODIPY dye (SBDPiR690) generates singlet oxygen without heavy halogen atom substituents. SBDPiR690 generates both singlet oxygen and fluorescence. To our knowledge, this is the first example of such a finding. To establish a structure-photophysical property relationship, we prepared SBDPiR analogs with electron-withdrawing groups at the para-position of the phenyl groups. The electron-withdrawing groups increased the HOMO-LUMO energy gap and singlet oxygen generation. Among the analogs, SBDPiR688, a CF3 analog, had an excellent dual functionality of brightness (82290 m(-1) cm(-1) ) and phototoxic power (99170 m(-1) cm(-1) ) comparable to those of Pc 4, due to a high extinction coefficient (211 000 m(-1) cm(-1) ) and balanced decay (Φflu =0.39 and ΦΔ =0.47). The dual functionality of the lead compound SBDPiR690 was successfully applied to preclinical optical imaging and for PDT to effectively control a subcutaneous tumor.

Ionic bonding of lanthanides, as influenced by d- and f-atomic orbitals, by core-shells and by relativity.

Lanthanide trihalide molecules LnX3 (X = F, Cl, Br, I) were quantum chemically investigated, in particular detail for Ln = Lu (lutetium). We applied density functional theory (DFT) at the nonrelativistic and scalar and SO-coupled relativistic levels, and also the ab initio coupled cluster approach. The chemically active electron shells of the lanthanide atoms comprise the 5d and 6s (and 6p) valence atomic orbitals (AO) and also the filled inner 4f semivalence and outer 5p semicore shells. Four different frozen-core approximations for Lu were compared: the (1s(2) -4d(10) ) [Pd] medium core, the [Pd+5s(2) 5p(6) = Xe] and [Pd+4f(14) ] large cores, and the [Pd+4f(14) +5s(2) 5p(6) ] very large core. The errors of LuX bonding are more serious on freezing the 5p(6) shell than the 4f(14) shell, more serious upon core-freezing than on the effective-core-potential approximation. The LnX distances correlate linearly with the AO radii of the ionic outer shells, Ln(3+) -5p(6) and X(-) -np(6) , characteristic for dominantly ionic Ln(3+) -X(-) binding. The heavier halogen atoms also bind covalently with the Ln-5d shell. Scalar relativistic effects contract and destabilize the LuX bonds, spin orbit coupling hardly affects the geometries but the bond energies, owing to SO effects in the free atoms. The relativistic changes of bond energy BE, bond length Re , bond force k, and bond stretching frequency vs do not follow the simple rules of Badger and Gordy (Re ∼BE∼k∼vs ). The so-called degeneracy-driven covalence, meaning strong mixing of accidentally near-degenerate, nearly nonoverlapping AOs without BE contribution is critically discussed.

Core-dependent and ligand-dependent relativistic corrections to the nuclear magnetic shieldings in MH4-n Y n (n = 0-4; M = Si, Ge, Sn, and Y = H, F, Cl, Br, I) model compounds.

The nuclear magnetic shieldings of Si, Ge, and Sn in MH(4-n) Y(n) (M = Si, Ge, Sn; Y = F, Cl, Br, I and n = 1-4) molecular systems are highly influenced by the substitution of one or more hydrogens by heavy-halogen atoms. We applied the linear response elimination of small components (LRESC) formalism to calculate those shieldings and learn whether including only a few of the leading relativistic correction terms is sufficient to be able to quantitatively reproduce the full relativistic value. It was observed that the nuclear magnetic shieldings change as the number of heavy halogen substituents and their weights vary, and the pattern of σ(M) generally does not exhibit the normal halogen dependence (NHD) behavior that can be seen in similar molecular systems containing carbon atoms. We also analyzed each relativistic correction afforded by the LRESC method and split them in two: core-dependent and ligand-dependent contributions; we then looked for the electronic mechanisms involved in the different relativistic effects and in the total relativistic value. Based on this analysis, we were able to study the electronic mechanism involved in a recently proposed relativistic effect, the "heavy atom effect on vicinal heavy atom" (HAVHA), in more detail. We found that the main electronic mechanism is the spin-orbit or σ p (T(3)) correction, although other corrections such as σ p (S(1)) and σ p (S(3)) are also important. Finally, we analyzed proton magnetic shieldings and found that, for molecules containing Sn as the central atom, σ(H) decreases as the number of heavy halogen substituents (of the same type: either F, Cl, or Br) increases, albeit at different rates for different halogens. σ(H) only increase as the number of halogen substituents increases if the halogen is iodine.

Structural/electronic properties and reaction energies of a series of mono- and bis-uranyl dihalides equatorially coordinated by N/O ligands.

Monometallic (UO2)(X)2(L)3 (L = pyridine (py), X = F (1), Cl (2), Br (3) and I (4); L = tetrahydrofuran (thf), X = Cl (5); L = pyrrole (pl), X = Cl (6)) as well as bimetallic [(UO2)(μ2-X)(X)(L)2]2 (L = py, X = F (7), Cl (8), Br (9) and I (10); L = thf, X = Cl (11); L = pl, X = Cl (12); μ 2 = doubly bridged) were examined using relativistic density functional theory. With changing from F, Cl, Br to I irregardless of in mono- or bis-uranyl complexes, bond lengths of U = O were calculated to be decreasing, resulting from strengthening of axial U = O bonds while weakening equatorial X → U coordination. This is further evidenced by calculated bond orders of U = O and stretching vibrational frequencies. A similar situation was is found in 2, 5 and 6 as well as in 8, 11 and 12, where N/O ligands are varied but the chlorine atoms are retained. The present study reveals that all these complexes have U(f)-character low-lying unoccupied orbitals, and their π*(U = O) antibonds are located on higher-energy orbitals. Complex 1 was calculated to show σ(U = O) bonding character for HOMO, and pyridine-character for other occupied orbitals; the fluorine ligand occurs in a relatively low-energy region. In contrast, the π(p) characters of heavier halogen atoms significantly contribute to most frontier molecular orbitals of 2, 3 and 4. Unlike this electronic feature of 2, complexes 5 and 6 exhibit mainly thf and pyrrole characters, respectively, for their high-lying occupied orbitals. Electronic structures of bisuranyl complexes 7-12, albeit a little more complicated, are revealed to be similar to those of the corresponding monouranyl complexes. Finally, energies of formation reactions of the above complexes were calculated and compared with available experimental results.

Abstracts of the 17th International Symposium on Bioluminescence and Chemiluminescence ‐ (ISBC 2012)

WARNING : The light-emitting molecular structures responsible for the chemiluminescence and fluorescence phenomena are not necessarily the same!

Effect of halogenated fluorescent compounds on bioluminescent reactions

The paper investigates an application of luminescent bioassays to monitor the toxicity of organic halides. Effects of xanthene dyes (fluorescein, eosin Y, and erythrosin B), used as model compounds, on bioluminescent reactions of firefly Luciola mingrelica, marine bacteria Photobacterium leiognathi, and hydroid polyp Obelia longissima were studied. Dependence of bioluminescence quenching constants on the atomic weight of halogen substituents in dye molecules was demonstrated. Bacterial bioluminescence was shown to be most sensitive to heavy halogen atoms involved in molecular structure; hence, it is suitable for construction of sensors to monitor toxicity of halogenated compounds. Mechanisms of bioluminescence quenching--energy transfer processes, collisional interactions, and enzyme-dye binding--were considered. Changes of bioluminescence (BL) spectra in the presence of the dyes were analyzed. Interactions of the dyes with enzymes were studied using fluorescence characteristics of the dyes in steady-state and time-resolved experiments. The dependences of fluorescence anisotropy of enzyme-bound dyes, the average fluorescence lifetime, and the number of exponential components in fluorescence decay on the atomic weight of halogen substituents were demonstrated. The results are discussed in terms of "dark effect of heavy halogen atom" in the process of enzyme-dye binding; hydrophobic interactions were assumed to be responsible for the effect.

STRUCTURAL AND ELECTRONIC PROPERTIES OF α-TiNX (X:F, Cl, Br, I): AN AB INITIO STUDY

The electronic and lattice properties of α-TiNX (X:F, Cl, Br, I) were investigated from first principles. Ab initio calculations for geometry optimization, electronic band structure and zone-center phonon calculations have been carried out by using plane-wave pseudopotential method which is not examined before. From the electronic structure calculation, band gaps have been found as 1.23 eV, 0.955 eV, 0.897 eV for TiNF , TiNCl , TiNBr while there is no band gap for TiNI . This result can separate TiNI from other metal nitride halides which are semiconductor. Band structure calculations showed that increasing the electropositivity of halogen atom in TiNX systems decreasing the fermi energy level or in other words shift the valance bonds to higher energy. Also zone center phonon modes show that the vibrational frequencies are increasing by atomic number of halogens. Heavier halogen atom makes the system vibrate more slowly and as expected to reduce vibrational frequency.

Understanding the NMR chemical shifts for 6-halopurines: role of structure, solvent and relativistic effects

A prototypical study of NMR chemical shifts in biologically relevant heteroaromatic compounds containing a heavy halogen atom is presented for two isomers of halogen-substituted purines. Complete sets of (1)H-, (13)C- and (15)N-NMR chemical shifts are determined experimentally in solution. Experimental results are complemented by quantum-chemical calculations that provide understanding of the trends in the chemical shifts for the studied compounds and which show how different physical effects influence the NMR parameters. Chemical shifts for isolated molecules are calculated using density-functional theory methods, the role of solvent effects is studied using polarised continuum models, and relativistic corrections are calculated using the leading-order Breit-Pauli perturbation theory. Calculated values are compared with the experimental data and the effects of structure, solvent and relativity are discussed. Overall, we observe a good agreement of theory and experiment. We find out that relativistic effects cannot be neglected even in the chlorine species when aiming at high precision and a good agreement with the experimental data. Relativity plays a crucial role in the bromine and iodine species. Solvent effects are of smaller importance for (13)C shifts but are shown to be substantial for particular (15)N shifts. The test of method performance shows that the BLYP and B3LYP functionals provide the most reliable computational results after inclusion of the solvent and relativistic effects while BHandHLYP may--depending on atom in question--slightly improve but mostly deteriorate the data. Ab initio Hartree-Fock suffers from triplet instability in the Breit-Pauli relativistic part while MP2 provides no clear improvement over DFT in the nonrelativistic region. This work represents the first full application of the Breit-Pauli perturbation theory to an organic chemistry problem.