Iodine Atoms Research Articles

Activity-Based Photosensitizers with Optimized Triplet State Characteristics Toward Cancer Cell Selective and Image Guided Photodynamic Therapy.

Activity-based theranostic photosensitizers are highly attractive in photodynamic therapy as they offer enhanced therapeutic outcome on cancer cells with an imaging opportunity at the same time. However, photosensitizers (PS) cores that can be easily converted to activity-based photosensitizers (aPSs) are still quite limited in the literature. In this study, we modified the dicyanomethylene-4H-chromene (DCM) core with a heavy iodine atom to get two different PSs (DCMO-I, I-DCMO-Cl) that can be further converted to aPS after simple modifications. The effect of iodine positioning on singlet oxygen generation capacity was also evaluated through computational studies. DCMO-I showed better performance in solution experiments and further proved to be a promising phototheranostic scaffold via cell culture studies. Later, a cysteine (Cys) activatable PS based on the DCMO-I core (DCMO-I-Cys) was developed, which induced selective photocytotoxicity along with a fluorescence turn-on response in Cys rich cancer cells.

Evaluation of radiative and Auger electron emission following K-shell vacancy creation in iodine

Emission produced by radiative and Auger cascade following a creation of the K-shell vacancy in the iodine atom is investigated by considering transitions among subconfigurations. Iodine is a widely used radionuclide with great therapeutic potential that can be exploited in antitumor treatment. The main branches of the cascade are identified. The radiative and Auger electron spectra of the cascade are investigated for all subconfigurations of the I+1s5p5 configuration. It is shown that the strongest group of lines in the Auger spectrum is formed at ∼1 eV by transitions from I2+ to I3+. Ionization stages up to I16+ are produced in the decay process. The study of evolution of charge states over time reveals that the final states of the cascade are reached in ∼10−13 s.

Visible-Light-Promoted Nickel-Catalyzed Cross-Coupling of Iodocarboranes with (Hetero)Arenes via Boron-Centered Carboranyl Radicals.

A general strategy for the generation of hypervalent boron-centered carboranyl radicals at the B(3), B(4), and B(9) positions has been developed for the first time via visible-light-promoted iodine atom abstraction from iodo-o-carboranes by low-valent nickel complex. These radicals react with various (hetero)arenes to afford a wide range of cage B-arylated carborane derivatives at room temperature in very good to excellent yields with a broad substrate scope. Their electrophilicities are dependent on the vertex charges of the cage and follow the order B(3) > B(4) > B(9). Both visible light and nickel catalyst are proved critical to the generation of boron-centered carboranyl radicals. The involvement of boron radicals is supported by control experiments. A reaction mechanism associated with these reactions is also proposed. This strategy offers a new protocol for the generation of boron-centered carboranyl radicals at the selected boron vertex, leading to a facile synthesis of a large class of cage boron substituted carborane molecules.

Iodinated Diketopiperazines: Synthesis and Biological Evaluation of Iodinated Analogues of Cyclo(L‐Tyrosine‐L‐Tyrosine) Peptides

AbstractWe developed a simple strategy to diiodinated tyrosine (Tyr) amino acid at the 3‐ and 5‐ positions from the commercially available Fmoc/Boc‐L‐Tyrosine monomer. The iodinated tyrosine monomer have been further adopted to generate a variety of iodinated Fmoc tyrosine dimers. Upon Fmoc elimination, we obtained diketopiperazine (DKP) analogues of Cyclo(L‐Tyr‐L‐Tyr) with varied number of iodine atoms. We also report the biological studies of these iodinated DKP analogues in three different cancer cell lines. We demonstrate that the number of iodine atoms in the Cyclo(L‐Tyr‐L‐Tyr) DKP analogues, and the presence of electron‐rich phenolic group are essential structural parameters to have pronounced cytotoxic activity in three different cancer cell lines.

Occurrence and fate of Adsorbable Organic Halogens (AOX) in two WWTPs from Romania.

Absorbable organic halogens (AOX) are a global parameter which refers to a group of chemical compounds that contain one or more chlorine, bromine or iodine atoms in their molecule and can easily adsorb on activated carbon. The global concern related to the occurrence of the AOX compounds in the environment is due to their toxic and mutagenic effects on aquatic organisms and their potential role as inhibitors of microorganism growth, even at AOX low concentrations. The purpose of this study was to analyze the presence, occurrence and composition of absorbable organic halogens in wastewater and sewage sludge. In addition, their genotoxicity effect on the environment was tested on a bacterial biological model. Daily mass loading, mass emission and fate of AOX parameter were investigated in two wastewater treatment plants (wastewater and sewage sludge samples) from Romania, Galati and Iasi. Their AOX daily mass loadings (151 and 55.4g/day/1000people) and mass emissions into the environment (47.8 and 23.5g/day/1000 people) for both locations were correlated with the concentration level of volatile organic compounds, chlorophenols, organochlorine pesticides and polychlorinated biphenyls from both wastewater and sewage sludge, respectively. Concentration levels of detected halogenated organic compounds (regulated by current standards) accounted only for a small percentage (3.70-14.5%) from the total AOX amount. An exception was observed in the case of dehydrated sludge samples where the identified compounds accounted for 80% of the AOX content from Iasi WWTP and 53% for Galati. Evaluating the genotoxic activity of AOX in sludge samples showed that genotoxicity was not induced up to 100µg/mL dehydrated sludge.

Mechanistic study on the coupling reaction of CO2 with propylene oxide catalyzed by (CH3 )4 PI·MgCl2.

The mechanistic study of CO2 coupling with propylene oxide (PO) into cyclic carbonate catalyzed by (CH3 )4 PI has been investigated using the B3 LYP/6-311++G (d, p)/B3 LYP/6-31G (d) level of theory for non-iodine atoms and LANL2DZ was used, together with its associated basis set for the iodine atom. Two hypothetical reaction mechanisms were proposed for the studied reaction and thermodynamic and kinetic parameters were computed for each step to determine the more favorable route. The density functional theory (DFT) study reveals that the reaction prefers to proceed through a three-step mechanism (pathway II) than a tri-molecular intermediate (pathway I) where the CO2 and the catalyst act simultaneously on the PO ring. The rate-determining step of the catalytic reaction is found to be the ring-opening step with an energy barrier of 27.1kcal/mol (pathway II) in the gas phase, which is kinetically more favorable than that of non-catalytic CO2 fixation with a relatively higher barrier of 63.7kcal/mol. The synergetic effect of MgCl2 is tested as a cocatalyst for the (CH3 )4 PI/MgCl2 catalyzed reaction and it gave a better result and minimized the activation energy for the reaction and the rate-determining step was the ring closure with the free energy of activation 18.8kcal/mol in the gas phase. The polarizable continuum model was used to account for the solvent effect, obtaining the best results of 23.1kcal/mol in water for pathway I and 16.5kcal/mol and 14.9kcal/mol in dimethyl sulfoxide for pathway II and binary system, respectively.

Forchlorfenuron and Novel Analogs Cause Cytotoxic Effects in Untreated and Cisplatin-Resistant Malignant Mesothelioma-Derived Cells.

Malignant mesothelioma (MM) is a currently incurable, aggressive cancer derived from mesothelial cells, most often resulting from asbestos exposure. The current first-line treatment in unresectable MM is cisplatin/pemetrexed, which shows very little long-term effectiveness, necessitating research for novel therapeutic interventions. The existing chemotherapies often act on the cytoskeleton, including actin filaments and microtubules, but recent advances indicate the ‘fourth’ form consisting of the family of septins, representing a novel target. The septin inhibitor forchlorfenuron (FCF) and FCF analogs inhibit MM cell growth in vitro, but at concentrations which are too high for clinical applications. Based on the reported requirement of the chloride group in the 2-position of the pyridine ring of FCF for MM cell growth inhibition and cytotoxicity, we systematically investigated the importance (cell growth-inhibiting capacity) of the halogen atoms fluorine, chlorine, bromine and iodine in the 2- or 3-position of the pyridine ring. The MM cell lines ZL55, MSTO-211H, and SPC212, and—as a control—immortalized Met-5A mesothelial cells were used. The potency of the various halogen substitutions in FCF was mostly correlated with the atom size (covalent radius); the small fluoride analogs showed the least effect, while the largest one (iodide) most strongly decreased the MTT signals, in particular in MM cells derived from epithelioid MM. In the latter, the strongest effects in vitro were exerted by the 2-iodo and, unexpectedly, the 2-trifluoromethyl (2-CF3) FCF analogs, which were further tested in vivo in mice. However, FCF-2-I and, more strongly, FCF-2-CF3 caused rapidly occurring strong symptoms of systemic toxicity at doses lower than those previously obtained with FCF. Thus, we investigated the effectiveness of FCF (and selected analogs) in vitro in MM cells which were first exposed to cisplatin. The slowly appearing population of cisplatin-resistant cells was still susceptible to the growth-inhibiting/cytotoxic effect of FCF and its analogs, indicating that cisplatin and FCF target non-converging pathways in MM cells. Thus, a combination therapy of cisplatin and FCF (analogs) might represent a new avenue for the treatment of repopulating chemo-resistant MM cells in this currently untreatable cancer.

Tuning Adsorption-Induced Responsiveness of a Flexible Metal–Organic Framework JUK-8 by Linker Halogenation

Flexible stimuli-responsive metal–organic frameworks have become promising candidates for numerous applications in gas-related technologies; however, the methods of fine tuning their responses are still limited and sought after. In this work, we demonstrate control over the adsorption properties of a flexible platform by incorporating halogen substituents (X = F, Cl, Br, I) into an eightfold interpenetrated isoreticular series [Zn(oba)(X-pip)]n (JUK-8X; X-pip = 4-pyridyl-functionalized benzene-1,3-dicarbo-5-halogenohydrazide; oba2– = 4,4′-oxydibenzoic carboxylate). The introduced halogen atoms allow for precise tuning of CO2 gate-opening pressures from p/p0 = 0.08 for the parental JUK-8 to 0.78 for the chlorine-functionalized JUK-8Cl. The presence of fluorine or chlorine substituent in the X-pip linker practically does not influence the maximum molar CO2 uptake as compared to JUK-8, whereas larger bromine or iodine atoms increase this uptake by 59 and 48%, respectively. Utilizing in situ powder X-ray diffraction (PXRD) during CO2 adsorption for a model JUK-8F, we propose a detailed mechanism of phase transitions including positions of the adsorbed gas molecules for the two loaded phases. Density functional theory calculations supported by in situ PXRD measurements at a saturation pressure shed light on the unusual CO2 adsorption properties of JUK-8Br and JUK-8I. Overall, our report demonstrates the use of halogen interactions for the control of a gas-responsive system and provides insightful guidance for the further development of flexible, adaptable materials.

Microwave-enhanced synthesis of 26-amino-22-oxocholestanes and their cytotoxic activity

The synthesis of a series of 26-amino-22-oxocholestanes derived from diosgenin was accomplished via the substitution of an iodine atom at C-26 by primary and secondary amines. The reactions were conducted in refluxing acetonitrile and through microwave-assisted heating. The latter shows significant improvements in terms of reaction times going from hours to a few minutes or even seconds for completion. Only one of the selected amines, 4-aminourazole, did not yield the substitution product and the imine formation pathway was investigated instead, achieving the 26-iminourazole-22-oxocholestane. All the final products have been characterized and the cytotoxic activity of three of them has been evaluated in SiHa, MCF-7 and MDA tumor cell lines by the sulforhodamine B assay.

Anticooperativity of Multiple Halogen Bonds and Its Effect on Stoichiometry of Cocrystals of Perfluorinated Iodobenzenes.

To investigate influences on the topicity of perfluorinated halobenzenes as halogen bond (XB) donors in the solid state, we have conducted a database survey and prepared 18 novel cocrystals of potentially ditopic (13ditfb, 14ditfb) and tritopic (135titfb) XB donors with 15 monotopic pyridines. 135titfb shows high tendency to be mono- or ditopic, but with strong bases it can act as a tritopic XB donor. DFT calculations have shown that binding of a single acceptor molecule on one of the iodine atoms of the XB donor reduces the ESPmax on the remaining iodine atoms and dramatically decreases their potential for forming further halogen bonds, which explains both the high occurrence of crystal structures where the donors do not achieve their maximal topicity and the observed differences in halogen bond lengths. Despite the fact that this effect increases with the basicity of the acceptor, when the increase of halogen bond energy due to the basicity of the acceptor compensates its decrease due to the reduction of the acidity of the donor, it enables strong bases to form cocrystals in which a potentially polytopic XB donor achieves its maximal topicity.

Continuous Pyrolysis Microreactors: Hot Sources with Little Cooling? New Insights Utilizing Cation Velocity Map Imaging and Threshold Photoelectron Spectroscopy.

Resistively heated silicon carbide microreactors are widely applied as continuous sources to selectively prepare elusive and reactive intermediates with astrochemical, catalytic, or combustion relevance to measure their photoelectron spectrum. These reactors also provide deep mechanistic insights into uni- and bimolecular chemistry. However, the sampling conditions and effects have not been fully characterized. We use cation velocity map imaging to measure the velocity distribution of the molecular beam signal and to quantify the scattered, rethermalized background sample. Although translational cooling is efficient in the adiabatic expansion from the reactor, the breakdown diagrams of methane and chlorobenzene confirm that the molecular beam component exhibits a rovibrational temperature comparable with that of the reactor. Thus, rovibrational cooling is practically absent in the expansion from the microreactor. The high rovibrational temperature also affects the threshold photoelectron spectrum of both benzene and the allyl radical in the molecular beam, but to different degrees. While the extreme broadening of the benzene TPES suggests a complex ionization mechanism, the allyl TPES is in fact consistent with an internal temperature close to that of the reactor. The background, room-temperature spectra of both are superbly reproduced by Franck-Condon simulations at 300 K. On the one hand, this leads us to suggest that room-temperature reference spectra should be used in species identification. On the other hand, analysis of the allyl iodide pyrolysis data shows that iodine atoms often recombine to form molecular iodine on the chamber surfaces. Such sampling effects may distort the chemical composition of the scattered background with respect to the molecular beam signal emanating directly from the reactor. This must be considered in quantitative analyses and kinetic modeling.

Anti-Markovnikov Iodofluorination of Alkenes.

The fluorination of alkenes with electrophilic N-F type reagents usually occurs through a Markovnikov-type addition, and the anti-Markovnikov-type addition may require the use of a transition metal catalyst or an expensive catalyst. Herein we describe a convenient anti-Markovnikov iodofluorination of alkenes with Selectfluor/n Bu4 NI. A wide substrate scope and good functional group tolerance were observed. The process allows for the construction of various C-F bonds, especially tertiary C-F bonds. The remarkable features make this protocol attractive, including convenient operations, simple reaction conditions, and the installation of an iodine atom which provides possibilities for further transformations.

Pushing the Efficiency of High Open-Circuit Voltage Binary Organic Solar Cells by Vertical Morphology Tuning.

The tuning of vertical morphology is critical and challenging for organic solar cells (OSCs). In this work, a high open‐circuit voltage (V OC) binary D18‐Cl/L8‐BO system is attained while maintaining the high short‐circuit current (J SC) and fill factor (FF) by employing 1,4‐diiodobenzene (DIB), a volatile solid additive. It is suggested that DIB can act as a linker between donor or/and acceptor molecules, which significantly modifies the active layer morphology. The overall crystalline packing of the donor and acceptor is enhanced, and the vertical domain sizes of phase separation are significantly decreased. All these morphological changes contribute to exciton dissociation, charge transport, and collection. Therefore, the best‐performing device exhibits an efficiency of 18.7% with a V OC of 0.922 V, a J SC of 26.6 mA cm−2, and an FF of 75.6%. As far as it is known, the V OC achieved here is by far the highest among the reported OSCs with efficiencies over 17%. This work demonstrates the high competence of solid additives with two iodine atoms to tune the morphology, particularly in the vertical direction, which can become a promising direction for future optimization of OSCs.

Cover Feature: Influence of Substituents in the Benzene Ring on the Halogen Bond of Iodobenzene with Ammonia (ChemPhysChem 6/2022)

The Cover Feature depicts the effect of substituents placed ortho, meta, and para to the iodine atom on various aspects of this halogen bond (XB). Electron-withdrawing groups strengthen the XB, particularly those placed in an ortho position. The bond strength correlates with the NMR chemical shift of the N and C atoms, as well as the JIN coupling constant. More information can be found in the Research Article by Steve Scheiner and Sarah Hunter.

Ultrasonication enhanced photocatalytic solvent-free reversible deactivation radical polymerization up to high conversion with good control

Focusing on energy-saving and environmentally-friendly polymerization engineering, ultrasonication and light were employed as coupled physical stimuli to regulate solvent-free reversible addition fragmentation chain transfer polymerization (RAFT), atom transfer radical polymerization (ATRP) and iodine transfer polymerization (ITP). The solvent-free polymerizations of (meth)acrylate under different conditions were performed with good control even at high monomer conversion (>90%), yielding polymers with low values of dispersity and retention of chain-end functionality. Kinetic experiments and mechanistic insights confirmed that light triggered different photocatalytic pathways (e.g. oxidative quenching cycle for RAFT, reductive quenching cycle for ATRP, photogenerated radical species for ITP) to initiate and mediate the solvent-free polymerizations and ultrasonication was used as an effective process intensification method to improve the diffusive of photocatalysts and their derivatives to alleviate the diffusional limitations for keeping good control up to high monomer conversion. This as-developed strategy is proved to be an efficient technology to produce well-defined polymers without complicated processes of products separation from solvent and residual monomer removal.

Pressure-induced phase transition and increase of oxygen-iodine coordination in magnesium iodate

The structural and vibrational behavior of $\mathrm{Mg}{({\mathrm{IO}}_{3})}_{2}$ under compression has been investigated via a combination of high-pressure (HP) synchrotron x-ray diffraction (XRD), Raman scattering, and infrared spectroscopy experiments as well as first-principles ab initio calculations. In this paper, we reveal that $\mathrm{Mg}{({\mathrm{IO}}_{3})}_{2}$ undergoes a pressure-induced phase transition between 7.5 and 9.7 GPa at ambient temperature from a monoclinic (space group $P{2}_{1}$) to a trigonal (space group P3) structure. $\mathrm{Mg}{({\mathrm{IO}}_{3})}_{2}$ also exhibits the gradual formation of additional bonds between iodine and oxygen atoms in neighboring ${\mathrm{IO}}_{3}^{\ensuremath{-}}$ units with increasing pressure, thereby increasing the oxygen-iodine coordination from 3 to 6. The bond formation under compression is a consequence of the existence of lone electron pairs on the iodine cation. To accommodate the additional bonds, the I--O bonds within the original ${[{\mathrm{IO}}_{3}]}^{\text{--}}$ trigonal pyramids increase in length under increasing compression. The appearance of additional Raman modes at 7.7 GPa and infrared modes at 9.6 GPa supports the phase transition observed in XRD experiments. Interestingly, the lengthening of I--O bonds causes a softening of several Raman modes under compression. We provide the crystal structure of the HP phase, the pressure-volume equations of state for both low- and HP phases, and the symmetry assignment of the Raman- and infrared-active modes of both phases.

Fibril Structure Demonstrates the Role of Iodine Labelling on a Pentapeptide Self-Assembly.

Iodination has long been employed as a successful labelling strategy to gain structural insights into proteins and other biomolecules via several techniques, including Small Angle X‐ray Scattering, Inductively Coupled Plasma Mass Spectrometer (ICP‐MS), and single‐crystal crystallography. However, when dealing with smaller biomolecular systems, interactions driven by iodine may significantly alter their self‐assembly behaviour. The engineering of amyloidogenic peptides for the development of ordered nanomaterials has greatly benefitted from this possibility. Still, to date, iodination has exclusively been applied to aromatic residues. In this work, an aliphatic bis‐iodinated amino acid was synthesized and included into a custom pentapeptide, which showed enhanced fibrillogenic behaviour. Peptide single crystal X‐ray structure and powder X‐ray diffraction on its dried water solution demonstrated the key role of iodine atoms in promoting intermolecular interactions that drive the peptide self‐assembly into amyloid fibrils. These findings enlarge the library of halogenated moieties available for directing and engineering the self‐assembly of amyloidogenic peptides.

Diaryliodoniums as Hybrid Hydrogen- and Halogen-Bond-Donating Organocatalysts for the Groebke-Blackburn-Bienaymé Reaction.

Dibenziodolium and diphenyliodonium triflates display high catalytic activity for the multicomponent reaction that leads to a series of imidazopyridines. Density functional theory (DFT) calculations indicate that both the salts can play the role of hybrid hydrogen- and halogen-bond-donating organocatalysts, which electrophilically activate the carbonyl and imine groups during the reaction process. The ortho-H atoms in the vicinal position to the I atom play a dual role: forming additional noncovalent bonds with the ligated substrate and increasing the maximum electrostatic potential on the σ-hole at the iodine atom owing to the effects of polarization. Dibenziodolium triflate exhibits higher catalytic activity, and the results obtained from 1H nuclear magnetic resonance (NMR) titrations, in conjunction with those from DFT calculations, indicate that this could be explained in terms of the additional energy required for the rotation of the phenyl ring in the diphenyliodonium cation during ligation of the substrate.

Convenient Approach to Bicyclic Sultams

AbstractA method for the synthesis of aminomethyl-substituted five-membered sultams has been developed. The aminomethyl sultams were synthesized from the corresponding iodomethyl derivatives by nucleophilic substitution of the iodine atom with sodium azide followed by reduction on Pd/C. This method was further expanded to side-chain-substituted sultams, starting from amino acid esters, to obtain aminomethyl-containing bicycles. The simple practical procedure and available starting amino acid esters, including chiral examples, make various bicyclic sultams readily available.

Ultrasensitive and Robust 120keV Hard X-Ray Imaging Detector based on Mixed-Halide Perovskite CsPbBr3- n In Single Crystals.

The relatively low resistivity and severe ion migration in CsPbBr3 significantly degrade the performance of X-ray detectors due to their high detection limit and current drift. The electrical properties and X-ray detection performances of CsPbBr3 -nIn single crystals are investigated by doping the iodine atoms into the melt-grown CsPbBr3 . The resistivity of CsPbBr3 -nIn single crystals increases from 3.6 × 109 (CsPbBr3 ) to 2.2 × 1011 (CsPbBr2 I) Ω cm, restraining the leak current and decreasing the detection limit of the detector. Additionally, CsPbBr3 -nIn single crystals exhibit stable dark currents, arising from their high ion migration activation energy. A record sensitivity of 6.3 × 104 µC Gy-1 cm-2 (CsPbBr2.9 I0.1 ) and a low detection limit of 54 nGy s-1 (CsPbBr2 I) are achieved by CsPbBr3 -nIn single crystals for the 120 keV hard X-ray detection under a 5000 V cm-1 electrical field. The CsPbBr2.9 I0.1 detector shows a stable current response with a dark current density of 0.58 µA cm-2 for 30 days and clear imaging for 120 keV Xrays at ambient conditions. The effective iodine atom doping strategy makes the CsPbBr3 -nIn single crystals promising for reproducible high-energy hard X-ray imaging systems.