Introduction Of Halogen Atoms Research Articles

Halogen-modulated mechanical force-induced luminescence enhancement and chromism of AIE-active tetraphenylethylene-based chalcone derivatives

In this paper, four new tetraphenylethylene-based chalcone derivatives (E)-1-phenyl-3-(4-(1,2,2-triphenylvinyl)phenyl)prop-2-en-1-one (PLPE), (E)-1-(4-fluorophenyl)-3-(4-(1,2,2-triphenylvinyl)phenyl)prop-2-en-1-one (PLPE-F),(E)-1-(4-chlorophenyl)-3-(4-(1,2,2-triphenylvinyl)phenyl)prop-2-en-1-one (PLPE-Cl), (E)-1-(4-bromophenyl)-3-(4-(1,2,2-triphenylvinyl)phenyl)prop-2-en-1-one (PLPE-Br) with different halogen substitutions were reported, and the effects of halogens on their photophysical properties, aggregation-induced emission behaviors and mechano-responsive luminescent properties were systematically investigated. Interestingly, aggregation-induced emission enhancement (AIEE) behaviors were observed for PLPE, PLPE-F, PLPE-Cl, and PLPE-Br. Moreover, upon grinding, all of the four compounds displayed mechanical force-induced luminescence enhancement and red-shifted behaviors, which was found to be reversible in the case of fuming with dichloromethane (DCM) vapors or heat treatment. In particular, upon grinding, PLPE-F showed the highest contrast fluorescence response behaviors (red-shifted 49 nm and solid fluorescence quantum yield increased 20-fold). Furthermore, the results of powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and field emission scanning electron microscopy (FESEM) measurements indicated that reversible phase transitions between the ordered crystalline state and the disordered amorphous form was crucial to their interesting mechanical force-induced luminescence enhancement and chromism. And the obvious red shifts of fluorescence emission are ascribed to the increased molecular conjugations via the planarization of molecular conformations. Moreover, halogen-substituted PLPE-F, PLPE-Cl, PLPE-Br have more twisted conformations than PLPE, which are responsible for their higher contrast mechanical force-induced luminescence chromism. Hence, the present study provides a new strategy to construct new advanced high-contrast mechanical force-induced luminescence enhancement and chromism luminescent materials with the introduction of halogen atoms.

Theoretical and electrochemical analysis of halogenated salmphen-type dinuclear copper(II) complex: The influence of halogenated ligands on bandgap

The predictable control of energy levels in coordination polymer is an essential issue in molecular science. To explore a simple and feasible strategy for tuning the energy levels of Schiff base materials, the present work synthesized a novel halogen-substituted cofacial Schiff base compound, CuII2(2-Cl-Salmphen)2 (Cu-2-Cl-Salmphen), and the non-halogenated analogue CuII2(H-Salmphen)2 (Cu-H-Salmphen) was introduced for comparison. Experimental results show that the introduction of halogen atoms can effectively increase the absorbance and decrease the impedance of the compound. Further theoretical analyses revealed that the substitutional halogen atoms can not only enlarge the conjugation area but also change the electron density and the molecular orbital energy levels, thus enabling modulation of the bandgap values of the compounds. Besides, NCI studies have demonstrated that the substitution of halogens can form additional intermolecular interaction pathways, adjusting the interactions between adjacent molecules.

Supramolecular Dimer as High-Performance pH Probe: Study on the Fluorescence Properties of Halogenated Ligands in Rigid Schiff Base Complex.

The development of high-performance fluorescence probes has been an active area of research. In the present work, two new pH sensors Zn-3,5-Cl-saldmpn and Zn-3,5-Br-saldmpn based on a halogenated Schiff ligand (3,5-Cl-saldmpn = N, N'-(3,3'-dipropyhnethylamine) bis (3,5-chlorosalicylidene)) with linearity and a high signal-to-noise ratio were developed. Analyses revealed an exponential intensification in their fluorescence emission and a discernible chromatic shift upon pH increase from 5.0 to 7.0. The sensors could retain over 95% of their initial signal amplitude after 20 operational cycles, demonstrating excellent stability and reversibility. To elucidate their unique fluorescence response, a non-halogenated analog was introduced for comparison. The structural and optical characterization suggested that the introduction of halogen atoms can create additional interaction pathways between adjacent molecules and enhance the strength of the interaction, which not only improves the signal-to-noise ratio but also forms a long-range interaction process in the formation of the aggregation state, thus enhancing the response range. Meanwhile, the above proposed mechanism was also verified by theoretical calculations.

Impact of donor halogenation on reorganization energies and voltage losses in bulk-heterojunction solar cells

The introduction of halogen atoms in the donor molecules in organic solar cells leads to a decrease in the reorganization energy, which in turn results in reduced non-radiative voltage losses and an improved open-circuit voltage in the devices.

Aggregation-induced emission and mechanofluorochromic materials based on the structural modification of 4,5,6-triaryl-4H-pyran skeleton

Although aggregation-induced emission (AIE)-active molecules with twisted structures have become the mainstream of mechanofluorochromic (MFC) materials, twisted molecular conformations do not necessarily lead to MFC properties. There have been some examples of failure based on 4,5,6-triaryl-4H-pyran skeleton. Herein, a series of 4,5,6-triaryl-4H-pyran derivatives were designed and synthesized to obtain fluorescent materials with both AIE and MFC characteristics. The results reveal that the introduction of triphenylamine endows all these propeller-type compounds with typical AIE properties originating from the restriction of intramolecular rotation, while the introduction of halogen atoms and the imidization of amino group are both conducive to the generation of the MFC activity by reducing the crystallization ability of derivatives. Furthermore, the red-shifted MFC phenomena are demonstrated to be ascribed to the planarization of molecular conformation caused by the crystalline-to-amorphous transition upon external pressure. This work confirms that appropriate crystallinity is very important for the candidate AIE-active compounds to exhibit MFC activities, which can be achieved by precise structural modification.

Halogen atoms induced reversible supramolecular assembly and pH-response of the fluorescence properties: Low driving force triggered fluorescence switch with high SNR and high stability

With the aim to investigate the influence of halogens on electronic structures and fluorescence properties, a new Salen type hetero-halogenated lanthanide complex [CeIV((±)3Br5Cl-salmen)2] (Ce-χ-L) was synthesized, and a set of optical properties were investigated. The complex was characterized by FT-IR, elemental analysis, UV and single-crystal X-ray diffraction, and structural analysis revealed that halogen atoms plays a significant role in inducing the complex into a special intramolecular ‘X’ structure as well as supramolecular dimer assemblies. Theoretical calculations revealed that the introduction of halogen atoms is important for lowering the energy level of HOMO-LUMO the lanthanide complexes Schiff base complexes and also increase pathways of intermolecular interactions. pH stability test revealed the supramolecular assemblies of Ce-χ-L is sensitive to the variation of pH environment, and the accompanied assemble and disassemble behaviors are closely related to the substitution of halogen atoms.

Manufacturing Approaches of New Halogenated Agrochemicals

AbstractTo ensure sustainability, the agrochemical industry is faced with enormous challenges, from provision of high‐quality food to water use, environmental impact and growing world population. The loss of agrochemicals due to consumer perception, changing grower needs and everchanging regulatory requirements is higher than the number of active ingredients being introduced into the market. Therefore, the development of new agrochemicals is essential, that can provide improved efficacy and favorable environmental profiles. In this context, introduction of halogen atoms into a molecule is an important tool to influence its physico‐chemical properties. Since 2010, around 81 % of the launched agrochemicals contain halogen atoms. This Review gives an overview of the latest generation of halogen‐containing agrochemicals introduced into the market over the past 10 years and describes manufacturing approaches of current halogen‐containing development candidates.

Natural and Synthetic Halogenated Amino Acids-Structural and Bioactive Features in Antimicrobial Peptides and Peptidomimetics.

The 3D structure and surface characteristics of proteins and peptides are crucial for interactions with receptors or ligands and can be modified to some extent to modulate their biological roles and pharmacological activities. The introduction of halogen atoms on the side-chains of amino acids is a powerful tool for effecting this type of tuning, influencing both the physico-chemical and structural properties of the modified polypeptides, helping to first dissect and then rationally modify features that affect their mode of action. This review provides examples of the influence of different types of halogenation in amino acids that replace native residues in proteins and peptides. Examples of synthetic strategies for obtaining halogenated amino acids are also provided, focusing on some representative compounds and their biological effects. The role of halogenation in native and designed antimicrobial peptides (AMPs) and their mimetics is then discussed. These are in the spotlight for the development of new antimicrobial drugs to counter the rise of antibiotic-resistant pathogens. AMPs represent an interesting model to study the role that natural halogenation has on their mode of action and also to understand how artificially halogenated residues can be used to rationally modify and optimize AMPs for pharmaceutical purposes.

Recent Advances in Molecular Design of Organic Thermoelectric Materials

Recent Advances in Molecular Design of Organic Thermoelectric Materials

Tuning the activity of known drugs via the introduction of halogen atoms, a case study of SERT ligands - Fluoxetine and fluvoxamine.

The selective serotonin reuptake inhibitors (SSRIs), acting at the serotonin transporter (SERT), are one of the most widely prescribed antidepressant medications. All five approved SSRIs possess either fluorine or chlorine atoms, and there is a limited number of reports describing their analogs with heavier halogens, i.e., bromine and iodine. To elucidate the role of halogen atoms in the binding of SSRIs to SERT, we designed a series of 22 fluoxetine and fluvoxamine analogs substituted with fluorine, chlorine, bromine, and iodine atoms, differently arranged on the phenyl ring. The obtained biological activity data, supported by a thorough in silico binding mode analysis, allowed the identification of two partners for halogen bond interactions: the backbone carbonyl oxygen atoms of E493 and T497. Additionally, compounds with heavier halogen atoms were found to bind with the SERT via a distinctly different binding mode, a result not presented elsewhere. The subsequent analysis of the prepared XSAR sets showed that E493 and T497 participated in the largest number of formed halogen bonds. The XSAR library analysis led to the synthesis of two of the most active compounds (3,4-diCl-fluoxetine 42, SERT Ki=5nM and 3,4-diCl-fluvoxamine 46, SERT Ki=9nM, fluoxetine SERT Ki=31nM, fluvoxamine SERT Ki=458nM). We present an example of the successful use of a rational methodology to analyze binding and design more active compounds by halogen atom introduction. 'XSAR library analysis', a new tool in medicinal chemistry, was instrumental in identifying optimal halogen atom substitution.

Synthesis and properties of halogen-containing macrocyclic anthraquinone imines – chemosensors for metal cations

New crown-containing imines of 1-hydroxyanthraquinone with chlorine and fluorine atoms in the anthraquinone nucleus were synthesized. For the first time, the thermal and photochemical stages of synthesis are carried out in the solid state (without a solvent). The features of complexation of new chemosensors with cations of alkaline and alkaline earth metals were studied by spectrophotometry. It is shown that the introduction of halogen atoms in the anthraquinone nucleus leads to a significant spectral response. The obtained compounds are tested as components of test systems for visual determining the presence of alkaline earth metal cations in aqueous media.

Status and outlook for acaricide and insecticide discovery.

To guarantee sustainability and progress, the agrochemical industry is faced with several major challenges. Currently, loss of active ingredients due to consumer perception, changing grower needs and ever‐changing regulatory requirements is far higher than the number being introduced into the market. Therefore, there is a need to develop new products that can provide improved efficacy, selectivity and favorable environmental profiles. Strategies to achieve these goals are the search for acaricides and insecticides with new modes of action, or the discovery of novel molecules with activity on the most attractive target sites having resistance breaking properties against pest species. In this context, the introduction of halogen atoms or asymmetric centers into an active ingredient remains an important tool to modulate their properties, but so too is the pro‐pesticide concept. This review gives an overview of agrochemicals launched over the past 8 years, reflects new insights into known mechanisms of action, and describes the status and outlook for acaricide and insecticide discovery.

Design and synthesis of 7-diethylaminocoumarin-based 1,3,4-oxadiazole derivatives with anti-acetylcholinesterase activities

Twelve novel 7-diethylaminocoumarin-based 1,3,4-oxadiazole derivatives were synthesized via iodine-mediated oxidative cyclisation and confirmed by 1H NMR, 13C NMR and HRMS. The result of these derivatives' activities inhibiting acetylcholinesterase in vitro showed that 4 g and 4i had moderate inhibitory activities with 69.19% and 65.06%, respectively. The preliminary structure-activity relationships revealed that introduction of halogen atom on the para-position of phenyl of 7-diethylaminocoumarin-based 1,3,4-oxadiazole derivatives could enhance their activities. Molecular docking study suggested that 4 g possessed an optimal docking pose with interactions inside AChE.

Halogenation of the N-Terminus Tyrosine 10 Promotes Supramolecular Stabilization of the Amyloid-β Sequence 7-12.

Here, we demonstrate that introduction of halogen atoms at the tyrosine 10 phenol ring of the DSGYEV sequence derived from the flexible amyloid‐β N‐terminus, promotes its self‐assembly in the solid state. In particular, we report the crystal structures of two halogen‐modified sequences, which we found to be stabilized in the solid state by halogen‐mediated interactions. The structural study is corroborated by Non‐Covalent Interaction (NCI) analysis. Our results prove that selective halogenation of an amino acid enhances the supramolecular organization of otherwise unstructured biologically‐relevant sequences. This method may develop as a general strategy for stabilizing highly polymorphic peptide regions.

Synthesis and Activity Investigation of Novel 1H-Purin-6(9H)-one and 3H-Imidazo[4,5-d][1,2,3]triazin-4(7H)-one Derivatives.

Novel 1H-purin-6(9H)-one (D) and 3H-imidazo[4,5-d][1,2,3]trazin-4(7H)-one (E) derivatives were designed, synthesized, and characterized by 1H NMR, 13C NMR and high-resolution mass spectrometry spectra. Their herbicidal activity bioassay showed that compound 7d exhibited relatively good activity with 70.4% inhibition rate against Amaranthus retroflexus in postemergence treatments at 1500 g/ha. Antitumor activity indicated that most of the title compounds displayed potent antitumor activity at 20 μM, among all of the promising compounds possessing lower IC50 values than that of temozolomide, compound 7i demonstrated highest activity inhibiting both HepG-2 and U-118 MG cell lines with IC50 values of 2.0 and 3.8 μM, respectively. The structure–activity relationship analysis revealed that introduction of halogen atoms, a bulky bridging bond between benzene ring and nitrogen atom, longer R2 substituents could contribute to the improvement of antitumor activity. Analysis suggested that compound 7i might have potential as new highly active antitumor agent. Overall, D series had better anticancer activities than E series derivatives.

Molecular dynamics investigation of halogenated amyloidogenic peptides.

Besides their biomolecular relevance, amyloids, generated by the self-assembly of peptides and proteins, are highly organized structures useful for nanotechnology applications. The introduction of halogen atoms in these peptides, and thus the possible formation of halogen bonds, allows further possibilities to finely tune the amyloid nanostructure. In this work, we performed molecular dynamics simulations on different halogenated derivatives of the β-amyloid peptide core-sequence KLVFF, by using a modified AMBER force field in which the σ-hole located on the halogen atom is modeled with a positively charged extra particle. The analysis of equilibrated structures shows good agreement with crystallographic data and experimental results, in particular concerning the formation of halogen bonds and the stability of the supramolecular structures. The modified force field described here allows describing the atomistic details contributing to peptides aggregation, with particular focus on the role of halogen bonds. This framework can potentially help the design of novel halogenated peptides with desired aggregation propensity. Graphical abstract Molecular dynamics investigation of halogenated amyloidogenic peptides.

Effect of Element Iodine on the Cell Membrane Transportability of Fluorescent Polymers and Lysosome-Targeted Cell Imaging

Fluorescence cell staining has become an important tool in biology for sensing and imaging applications. Surprisingly, the introduction of halogen atoms, especially iodine atoms, into small molecules’ framework is able to enhance the cellular uptake of fluorescent objects. However, for these iodo-containing fluorescent probes, the inherent disadvantages, such as water insolubility, high toxicity, and aggregation-caused quenching, prevent them from extensive applications. Furthermore, iodination of organic molecules is really difficult to produce. In our research work, we synthesized fluorescence probes by a copolymerization method, by which the water-soluble copolymers of P-TPE, P-TPE-I1 P-TPE-I2, and P-TPE-I3 with different iodine element contents were synthesized. The study on fluorescence performances demonstrated that these polymers are of high fluorescence quantum yields and long fluorescence lifetimes (up to 15 ns). Both of these characteristics are very beneficial to fluorescence probes being used ...

Halogen‐Mediated Membrane Transport: An Efficient Strategy for the Enhancement of Cellular Uptake of Synthetic Molecules

The poor uptake of fluorescent probes and therapeutics by mammalian cells is a major concern in biological applications ranging from fluorescence imaging to drug delivery in living cells. Although gaseous molecules such as oxygen and carbon dioxide, hydrophobic substances such as benzene, and small polar but uncharged molecules such as water and ethanol can cross the cell plasma membrane by simple passive diffusion, many synthetic as well as biological molecules require specific membrane transporters and channel proteins that control the traffic of these molecules into and out of the cell. This work reports that the introduction of halogen atoms into a series of fluorescent molecules remarkably enhances their cellular uptake, and that their transport can be increased to more than 95 % by introducing two iodine atoms at appropriate positions. The nature of the fluorophore does not play a major role in the cellular uptake when iodine atoms are present in the molecules, as compounds bearing naphthalimide, coumarin, BODIPY, and pyrene moieties show similar uptakes. Interestingly, the introduction of a maleimide-based fluorophore bearing two hydroxyethylthio moieties allows the molecules to cross the plasma and nuclear membranes, and the presence of iodine atoms further enhances the transport across both membranes. Overall, this study provides a general strategy for enhancing the uptake of organic molecules by mammalian cells.

Halogen-substituted triphenylamine derivatives with intense mechanoluminescence properties

Three TPA derivatives show different ML effects due to the various electronic structures modulated by the introduction of halogen atoms.

Enhanced mechanofluorochromic properties of 1,4-dihydropyridine-based fluorescent molecules caused by the introduction of halogen atoms

Halogen-substituted 1,4-dihydropyridine derivatives exhibit higher contrast mechanofluorochromic properties than the derivative without a halogen atom because of more twisted conformations and looser stacking arrangements.