Log Ka Research Articles

Interactions between dissolved organic matter with different molecular weights and nonylphenol in surface water bodies

Dissolved organic matter (DOM) has a complex composition, which can interact with various pollutants and affect the removal of pollutants. Therefore, a thorough understanding of the interaction between the encccvironmental hormone nonylphenol (NP) and DOM is crucial for environmental impact and development. In this study, the interaction was investigated by means of excitation emission matrix (EEM) fluorescence spectroscopy, UV–Vis spectroscopy, FT-IR spectroscopy, nuclear magnetic resonance (NMR) and complex model analysis. The interaction between different MW DOM and NP was verified by the spectral characterization data. According to the characterization analysis, the main components of DOM in water samples were proteinoid (C1, C2, C4) with MW < 1 k Da, and their binding capacity (log Ka value) and binding site number (n) showed the maximum values (3.37, 3.24, 3.26; 0.81, 1.22, 0.52). For the humus like substance (C3) with larger molecular weight, the log Ka value and the number of binding points n increased with increasing molecular weight, and the maximum values were 3.13 and 0.31, respectively. It can be seen that low molecular weight proteins have strong binding ability and binding sites with NP, and high molecular weight humus also have strong binding ability. Overall, the interaction between DOM and NP has molecular weight dependence and heterogeneity. The purpose of this study is to deeply understand the interaction characteristics of different MW DOM with NP, and to provide theoretical support and reference for the study of the removal effects of NP pollutants.

Synthesis and characterisation of dipyrromethene Cu(II) complexes: A preliminary DNA intercalation study

Copper complexes of the bilirubin bile pigment have been shown to affect DNA. It was suggested that the copper ions within these metal-bilirubin therapeutics bind to bilirubin through the two dipyrromethene moieties, thus highlighting the potential therapeutic impact of these dipyrromethene moieties. Here, we report the synthesis and characterization of two bilirubin biomimetic copper complexes, CuL1 and CuL2, featuring tetrahedral dipyrromethene moieties. DNA binding studies reveal significant affinities for both complexes, with CuL1 displaying a log Ka of 4.70 ± 0.02, with a corresponding Gibbs free energy change (ΔG) of –26.8 kJ/mol at 25 °C, indicating a moderate-to-high DNA affinity. CuL2 showed a slightly higher affinity with log Ka of 4.88 ± 0.02, with a corresponding ΔG of –27.4 kJ/mol at 25 °C. These experimental findings aligned closely with computational docking G-scores, which yielded –32.9 kJ/mol for CuL1 and –34.8 kJ/mol for CuL2, respectively. Viscosity, gel electrophoresis, and absorption studies support an intercalative binding mechanism, which was further confirmed by computational docking and molecular dynamics simulations. These findings suggest that copper dipyrromethene complexes may exert therapeutic effects through DNA interaction, warranting further investigation involving in vitro cell cultures for drug development potential.

Dipeptides Containing Pyrene and Modified Photochemically Reactive Tyrosine: Noncovalent and Covalent Binding to Polynucleotides.

Dipeptides 1 and 2 were synthesized from unnatural amino acids containing pyrene as a fluorescent label and polynucleotide binding unit, and modified tyrosine as a photochemically reactive unit. Photophysical properties of the peptides were investigated by steady-state and time-resolved fluorescence. Both peptides are fluorescent (Φf = 0.3-0.4) and do not show a tendency to form pyrene excimers in the concentration range < 10-5 M, which is important for their application in the fluorescent labeling of polynucleotides. Furthermore, both peptides are photochemically reactive and undergo deamination delivering quinone methides (QMs) (ΦR = 0.01-0.02), as indicated from the preparative photomethanolysis study of the corresponding N-Boc protected derivatives 7 and 8. Both peptides form stable complexes with polynucleotides (log Ka > 6) by noncovalent interactions and similar affinities, binding to minor grooves, preferably to the AT reach regions. Peptide 2 with a longer spacer between the fluorophore and the photo-activable unit undergoes a more efficient deamination reaction, based on the comparison with the N-Boc protected derivatives. Upon light excitation of the complex 2·oligoAT10, the photo-generation of QM initiates the alkylation, which results in the fluorescent labeling of the oligonucleotide. This study demonstrated, as a proof of principle, that small molecules can combine dual forms of fluorescent labeling of polynucleotides, whereby initial addition of the dye rapidly forms a reversible high-affinity noncovalent complex with ds-DNA/RNA, which can be, upon irradiation by light, converted to the irreversible (covalent) form. Such a dual labeling ability of a dye could have many applications in biomedicinal sciences.

Characterization of copper binding to different molecular weight fractions of dissolved organic matter in surface water

Dissolved organic matter (DOM) is a kind of substance with complex compositions and wide molecular weight distribution, which can strongly combine with various pollutants. Therefore, the binding characteristics of DOM and heavy metal pollutants can be studied specifically according to the binding characteristics of DOM and pollutants. In this study, DOM in surface water bodies was divided into three levels (MW < 1 kDa, 1 kDa < MW < 5 kDa, MW > 5 kDa) according to different molecular weights (MW). The binding properties were investigated by fluorescence spectrum analysis and complex model. Four components (C1–C4) were identified by PARAFAC. Among them, the contribution rate of protein-like components C1, C2 and C4 to the total fluorescence intensity reached more than 78%, and the log Ka values of low molecular weight components were the highest, which were 3.28, 3.14 and 3.47, respectively, indicating higher binding ability with Cu2+.With the decrease of molecular weight, the log Kb value increases, indicating that the complexation is more stable. The humic component C3 in high molecular weight has stronger binding stability with Cu2+, but the number of binding sites for C3 is 0.36, while that for C2 is 1.51, indicating that its binding sites and binding ability are relatively low. The results showed that the DOM ligand of Cu2+ in surface water showed a certain molecular weight dependence. In addition, different MW DOM lead to different pollution forms. Different properties of DOM ligand combined with Cu2+ were studied in order to control the migration, transformation, bioavailability, morphology and stability of heavy metal pollutants, and to provide theoretical support for the practical application management of surface water pollution control.

Towards the effects of moss-dominated biocrusts on surface soil aeration in drylands: Air permeability analysis and modeling

Soil aeration is an important factor influencing soil biological and biochemical processes because it directly affects soil microbial activity and respiration. As an important living skin of the soil, biocrusts strongly impact various soil properties and play a vital role in maintaining surface soil structure and multifunctionality. Although there are several studies concerning the effects of biocrusts on soil respiration processes, it is still not well understood how biocrusts affect air permeability (Ka) and soil aeration in drylands. In a semiarid climate region of the northern Chinese Loess Plateau, the Ka and air-filled porosity (εa) of moss-dominated biocrusts established on aeolian sand and loess soil were measured as a function of soil water content under laboratory and in situ conditions and compared to measurements of bare soils. The relative air permeability (Kra) of biocrusts and bare soils was further analyzed and estimated with commonly applied Kra models that are based on the soil water retention curve (SWRC), and the performance of these models was specifically assessed for biocrusts. The in situ measurements yielded a 51.8% and 76.7% higher Ka for the biocrust-colonized aeolian sand and loess soil, respectively, when compared to the bare soils. Correspondingly, in comparison to the bare soils, the εa of the biocrusts also increased by 38.0% for the aeolian sand and by 52.4% for the loess soil. The laboratory measurements showed an 8.5%–9.3% increase of Ka for the biocrust-colonized soils from wet to dry conditions when compared to their bare counterparts, which was mainly attributed to their higher fine particle and organic matter contents as well as to the moss rhizoids. Moreover, a positive linear relationship (R2 > 0.43) was found between the log Ka and log εa for both biocrusts and bare soils. Additionally, the biocrusts exhibited higher water content at almost all matric potentials in comparison to the bare soils. The Kra of biocrusts was 22.0% higher for aeolian sand and 42.1% higher for loess soil when compared to the bare soils. The van Genuchten-Burdine and Brooks and Corey-Burdine models performed best with regard to the estimation of Kra (RMSE ≤ 0.100, bias ≤ 0.018). In general, biocrusts may greatly increase surface soil aeration due to their higher Ka and εa, and the soil aeration status of biocrusts can be indirectly assessed through their effective degree of soil water saturation. Our findings suggest that biocrusts should be carefully considered in further studies of soil aeration related to biological processes and gas and vapor transport in dryland ecosystems.

A Pyrene-Rhodamine FRET couple as a chemosensor for selective detection of picric acid

Selective detection of nitroaromatic compounds such as Picric acid (PA), those being explosive materials and hazardous pollutants of environmental and biological concern is highly desirable. With the operational advantages of the chemosensing approach, a pyrene-rhodamine-B couple (1) was explored in this investigation as a ratiometric molecular probe for selective and sensitive detection of picric acid. The bi-fluorophoric probe displayed absorption and fluorescence enhancements along with colourless to reddish-brown colour transition as signaling responses in the selective presence of PA among all the nitro aromatic analyte investigated. The signaling module relies on PA- mediated modulation of various operational photo-physical processes such as (a) inhibition of photo-induced electron transfer (PET) operative from amino-donor to excited pyrene (b) a conformational translation through spiro-ring opening of rhodamine-B segment, and (c) initiation of Fluorescence Resonance Energy Transfer (FRET) between excited pyrene donor and ring-opened rhodamine acceptor. The ratio of fluorescence from both fluorophores (pyrene and Rhodamine) as output channel displayed sensitive signaling performance (LOD = 13.8 nM) in the detection of PA. The investigation that inferred to the PA-induced selectivity in signalling, higher binding affinity (log Ka≈11), a faster response time, and reversibility in signalling with a counter analyte and an operational pH range established the probe’s efficacy as a chemosensor for PA detection.

Further investigation of the irreversible floc breakup in flocculation kinetics modelling

Abstract Recent research has shown that the equilibrium between aggregation and breakup in flocculation kinetics modelling may not hold due to irreversible floc breakup. This work investigated the influence of the coagulant/particle ratio and average velocity gradient () in the occurrence of this phenomenon with a different water matrix than previous research. Jar test assays were conducted with low (≈15 NTU), medium (≈50 NTU) and high (≈100 NTU) turbidity synthetic raw water, using alum as coagulant and kaolin as primary particles. Results were analyzed using Argaman and Kaufman's model and values for KA (aggregation constant) and KB (breakup coefficient) were determined with the evolutionary convergence method. Model fitting was satisfactory when the Al/particle ratio varied between 10 and 27 mg Al3+/g. Outside this range, residual turbidity increased after equilibrium, attributed to the irreversible floc breakup process and not adequately described by the model. A two-factor analysis of variance (ANOVA) was conducted, and the results indicated a plausible correlation between pKA (–log KA) and Al/particle ratio. As for pKB (–log KB), the results indicated a possible correlation with both Al/particle ratio and . The results suggest that the irreversible floc breakup may occur regardless of the water matrix composition.

Predicting Pharmacokinetic Properties of Potential Anticancer Agents via Their Chromatographic Behavior on Different Reversed Phase Materials.

The Quantitative Structure-Activity Relationship (QSAR) methodology was used to predict biological properties, i.e., the blood–brain distribution (log BB), fraction unbounded in the brain (fu,brain), water-skin permeation (log Kp), binding to human plasma proteins (log Ka,HSA), and intestinal permeability (Caco-2), for three classes of fused azaisocytosine-containing congeners that were considered and tested as promising drug candidates. The compounds were characterized by lipophilic, structural, and electronic descriptors, i.e., chromatographic retention, topological polar surface area, polarizability, and molecular weight. Different reversed-phase liquid chromatography techniques were used to determine the chromatographic lipophilicity of the compounds that were tested, i.e., micellar liquid chromatography (MLC) with the ODS-2 column and polyoxyethylene lauryl ether (Brij 35) as the effluent component, an immobilized artificial membrane (IAM) chromatography with phosphatidylcholine column (IAM.PC.DD2) and chromatography with end-capped octadecylsilyl (ODS) column using aqueous solutions of acetonitrile as the mobile phases. Using multiple linear regression, we derived the statistically significant quantitative structure-activity relationships. All these QSAR equations were validated and were found to be very good. The investigations highlight the significance and possibilities of liquid chromatographic techniques with three different reversed-phase materials and QSARs methods in predicting the pharmacokinetic properties of our important organic compounds and reducing unethical animal testing.

In-Vitro and In-Silico Assessment of Per- and Polyfluoroalkyl Substances (PFAS) in Aqueous Film-Forming Foam (AFFF) Binding to Human Serum Albumin.

Drinking water contaminated by fluorosurfactant-based aqueous film-forming foams (AFFF) is a source of human exposure to poly- and perfluoroalkyl substances (PFAS). However, assessment of bioaccumulation potentials of diverse PFAS in commercial products such as AFFF have been insufficient and challenging, especially due to a lack of analytical standards. Here we explore the value of suspect screening, equilibrium dialysis, and molecular-docking simulations to identify potentially bioaccumulative PFAS. We exposed human serum albumin (HSA) protein to dilutions of a legacy AFFF produced by 3M in 1999 using equilibrium dialysis and screened in-vitro protein-binding affinities using high-resolution mass spectrometry (HRMS). Through suspect screening, we identified 32 PFAS and 18 hydrocarbon surfactants in the AFFF that bound to HSA. Quantification of noncovalent association constants for 26 PFAS standards confirmed that many PFAS, including the short-chain perfluoropropane sulfonic acid (log Ka= 4.1 ± 0.2 M−1), exhibit strong binding affinities with HSA. At least five PFAS in AFFF (including three PFAS with less than five perfluorocarbons) remained bound to the precipitated HSA pellet after extensive solvent washing—an indication of high PFAS binding potential. Three PFAS (PFBS, PFOS, and PFOA) were confirmed in the protein pellet with analytical standards and quantified after acid digestion—this sample fraction accounted for 5 to 20% of each compound mass in the sample. We calculated pseudo-bioconcentration factors (BCFpseudo) for PFAS that suspect screening flagged as noncovalently bound or potentially covalently bound. Most PFAS exhibiting high BCFpseudo, especially those with seven perfluorocarbons, contained a carboxylic acid or a sulfonic acid. Finally, we used molecular docking to simulate HSA binding affinities for 62 ligands (26 PFAS targets, 18 PFAS qualified in AFFF, and 18 hydrocarbon surfactants qualified in AFFF). We found that molecular docking can effectively separate HSA-binding and -nonbinding compounds in AFFF. In-vitro and in-silico approaches described in this study provide replicable, high-throughput workflows for assessing bioaccumulation potentials of diverse PFAS in commercial products.

Altered metal ion selectivity in signalling with heterocyclic tripodal receptor appended rhodamine-B derivatives

The rhodamine derivatives (2–7) were shown to exhibit metal ion complexation induced photophysical ‘turn-on’ signalling responses, where the selectivity in signalling were driven by stereo-electronic environment of the receptor units that structurally differ as derivatization of different heterocyclic units. The chromogenic and fluorogenic spectral enhancements of two order higher in logarithmic scale were observed in these tripodal receptor incorporated amino-ethyl-rhodamine probes, where substitution of a 2-[2-[(thiophen-2-yl-methyl)-(2-pyridinylmethyl)-amino]-ethyl]- (as in 3) has shown selectivity for Hg(II) ion, a 2-[2-[(furan-2-yl-methyl)-(2-pyridinyl methyl)-amino]-ethyl]- (as in 5) for Al(III) ion and a 2-[2-[(phen-2-ylmethyl)-(2-pyridinylmethyl)-amino]-ethyl]- (as in 7) for Fe(III) ion respectively. The higher order of association constants (log Ka > 9.0) of complexation, high sensitivity of detection(LOD < 2 nM) and higher rate of interaction between probe and metal ion (k ~ 0.001 s−1) have showed potential of these probes in selective detection of corresponding metal ions. In general, the investigations on complexation induced photophysical signalling in these probes in terms of selectivity and sensitivity of detection, association constants of complex formation, reversibility in signalling, execution at different pH range, kinetics of spiro-ring opening and theoretical structure elucidation have therefore put insights on their coordination mediated stereo-electronic environment to establish a rationality in structure-function correlation.

Anion Binding of a Cyclopeptide-Derived Molecular Cage in Aqueous Solvent Mixtures.

A molecular cage consisting of two cyclic hexapeptides with an alternating sequence of (2S,4S)-4-aminoproline and 6-aminopicolinic acid subunits, covalently linked via three diglycolic acid subunits, interacts with a variety of inorganic anions in acetonitrile/water. In the respective complexes, the anion resides in a cavity between the two cyclopeptide rings where it interacts with six converging NH groups. The cage binds sulfate anions in acetonitrile/water, 2 : 1 (v/v) with a log Ka of 6.7, ca. 2.5 orders of magnitude stronger than an analogous bis(cyclopeptide) with only one linker whose sulfate affinity log Ka amounts to 4.3. The preorganization induced by the three linking units is thus beneficial for sulfate binding. In addition, these linkers cause the dissociation of the sulfate complex to have a substantial Gibbs free energy of activation ΔG≠ of 68.9 kJ mol-1 and they also seem to affect anion selectivity as illustrated by the different effects some anions produce on the 1 H NMR spectra of the triply and singly-linked bis(cyclopeptides). Such anion binding cages represent promising scaffolds to mimic natural anion receptors such as the sulfate-binding protein.

Amino and hydroxy substitution influences pyrene–DNA binding

Polycyclic aromatic hydrocarbon (PAH)–DNA binding is an essential step in PAH-induced carcinogenesis. A large number of PAHs contain substituents, it is unclear whether functional groups will influence the PAH–DNA binding. Here, we investigated amino (-NH2) and hydroxy (-OH) substitution on pyrene–DNA binding. Because of the considerable effects of electrostatic surface potential (ESP), -NH2 substitution significantly facilitated binding by increasing the binding constant (log KA) from 4.14 L mol−1 to 12.31 L mol−1, while -OH substitution inhibited binding by reducing log KA to 3.68 L mol−1. Spectroscopy results revealed that pyrene and its derivatives were able to bind with thymine to induce DNA damage or double helix distortion. Quantum chemical calculations showed that -NH2 substitution induces hydrogen bond formation, thereby enhancing the binding of pyrene with DNA; moreover, binding force changes due to -OH substitution may not be an essential factor. All structural descriptors were not correlated with the quenching constant (KSV) or binding constant, indicating that changes in physicochemical properties shows no influence on pyrene–DNA binding. The results of this study will improve our understanding of the contribution of functional groups to PAH–DNA binding.

Novel computational approaches to retention modeling in dual hydrophilic interactions/reversed phase chromatography

The mixed-mode chromatographic behavior was estimated for imidazoline and serotonin receptor ligands, and their related compounds on dual hydrophilic/reversed phase stationary phase. The Box-Cox transformation was used to obtain the most suitable mathematical equations which describe the mixed-mode retention. Optimal equations were found for the optimization parameter (λ): λ = -1, λ = -0.5, λ = 0, λ = 0.5, and λ = 1. The proposed equations show satisfactory characteristics compared to standard multimodal and quadratic approaches.For a wide range of volume fractions of the mobile phase modifier, crossing between hydrophilic and reversed phase interactions (the turning point) was defined in terms of the minimal retention and the minimum value of the volume fraction of the aqueous eluent in the mobile phase. The cubic spline interpolation was used as a reference method for estimation of the turning point. It was found out that the newly proposed equations can be used as alternative mathematical forms for the description of the dual retention mechanism and for the evaluation of the turning point.Three new experimental descriptors of the mixed-mode retention were proposed. Two descriptors quantitatively characterize hydrophilic (log kH) and reversed phase (log kR) interactions, while the third one (log kA) refers to the average retention for the whole HILIC/RP range. It was established that the main factors which control dual nature of the mixed-mode retention are lipophilicity, dipol-dipol, van der Waals and hydrogen bonding interactions.It was concluded that the newly proposed estimations of the retention data reliably characterize the mixed-mode chromatographic behavior.

Effect of n-alkyl substitution on Cu(ii)-selective chemosensing of rhodamine B derivatives.

Rhodamine B hydrazide-based molecular probes (1-10) were synthesized by derivatization with n-alkyl chains of different lengths at the hydrazide amino end. These probes exhibited selective absorption (A∼557) and fluorescence (I∼580) 'off-on' signal transduction along with a colourless → magenta colour transition in the presence of Cu(ii) ions among all the competitive metal ions investigated. The effective coordination of these probes to Cu(ii) ions under the investigated environment forming [Cu·L]2+ (L = 1-5) and [Cu·L2]2+ (L = 6-10) complexes led to their spiro-ring opening, which in turn was expressed through signatory spectral peaks of ring-opened rhodamine. All these probes exhibited Cu(ii) selectivity in signalling despite structural modifications to the core receptor unit through variation of the nature of the alkyl substituents. However, the sensitivity of the signalling and kinetics of the spiro-ring opening varied and could be correlated with the number of carbon atoms present in the n-alkyl substituents. Structural elucidation with X-ray diffraction and X-ray photoemission spectroscopic analyses provided further insight into the structure-function correlation in their Cu(ii) complexes. These probes with Cu(ii) coordination showed selectivity in signalling, high complexation affinity (log Ka = 4.8-8.8), high sensitivity (LOD = 4.1-80 nM), fast response time (rate = 0.0017-0.0159 s-1) and reversibility with counter anions, which ascertained their potential utility as chemosensors for Cu(ii) ion detection.

Two novel classes of fused azaisocytosine-containing congeners as promising drug candidates: Design, synthesis as well as in vitro, ex vivo and in silico studies

Searching for new less toxic anticancer drug candidates is a big challenge from a medical point of view. The present investigation was aimed at describing two independent synthetic approaches based on isosteric replacements, spectroscopic characteristics, in vitro anticancer and ex vivo antihaemolytic activities of novel molecules (9–22) and correlations between their standardised lipophilicity indices, computed log Paverage values and pharmacokinetic descriptors. Two novel protocols for annelation of the triazinone template on hydrazinylideneimidazolidines (1–8) (showing a high reactivity towards electrophilic reagents, such as ethyl trifluoropyruvate and ethyl 3-methyl-2-oxobutyrate) were developed for the first time, giving rise to two original classes of highly conjugated azaisocytosine-containing molecules (9–16 and 17–22). Both syntheses proceeded under basic conditions to yield the most probable intermediates (e.g. hemiaminals and imines), which in refluxing two-component solvent mixtures or a suitable solvent cyclised through closing the triazinone ring on functionalised imidazolidines in both cases. All fused azaisocytosine-containing congeners were investigated with the purpose of preselecting possible drug candidates with a better selectivity that could be suitable for further more detailed drug development studies. The majority of test molecules revealed strong antiproliferative effects in most tumour cell cultures and they were more cytotoxic against tumour cells than anticancer drug – pemetrexed. These cytotoxicities may be associated with the activation of initiator and executioner caspases (confirmed for compound 12) which are inducers of apoptosis. Simultaneously, three bioisosteres bearing the trifluoromethyl moiety at the C-3 and the ortho substitution at the phenyl ring (10, 12 and 13) proved to be the most promising in terms of selectivity as they were less or equally toxic to normal cells as pemetrexed. It was shown that isosteric replacement of the ethyl group in antitumour active congeners by the trifluoromethyl or isopropyl group was favourable for the selectivity of the designed drug-like molecules. Almost all new compounds revealed the protective effects in an ex vivo model of oxidatively stressed rat erythrocytes (better or comparable than that of ascorbic acid/Trolox), proving that they are safe to red blood cells. The statistically significant and predictive QSAR equations were derived that describe relationships between some pharmacokinetic descriptors (such as log Ka, HSA, fu, brain, Caco-2, log Kp) and lipophilicity parameters of test molecules. Among all molecules with anticancer profile, the possible drug candidates seem to be 10, 12, 13, 19 and 21 which are the least toxic for normal cells, deprived of haemolytic effects on oxidatively-stressed red blood cells and have the optimum pharmacokinetic descriptors in terms of their lipophilicity parameters. Because of a high development potential they should be utilised in further more extended in vivo investigations aimed at developing novel less toxic anticancer agents.

Carbon Nanotubes Conjugated with Triazole-Based Tetrathiafulvalene-Type Receptors for C60 Recognition.

Fullerene receptors prepared by a twofold CuI -catalyzed azide-alkyne cycloaddition reaction with π-extended tetrathiafulvalene (exTTF) have been covalently linked to single-walled carbon nanotubes and multi-walled carbon nanotubes. The nanoconjugates obtained were characterized by several analytical, spectroscopic and microscopic techniques (TEM, FTIR, Raman, TGA and XPS), and evaluated as C60 receptors by using UV-Vis spectroscopy. The complexation between the exTTF-triazole receptor in the free state and C60 was also studied by UV-Vis and 1 H NMR titrations, and compared with analogous triazole-based tweezer-type receptors containing the electron-acceptor 11,11,12,12-tetracyano-9,10-anthraquinodimethane and benzene rings instead of exTTF motifs, providing in all cases very similar values for the association constant (log Ka ≈3.0-3.1). Theoretical density functional theory calculations demonstrated that the enhanced interaction between the host and the guest upon increasing the size of the π-conjugated arms of the tweezer is compensated by an increase in the energy penalty needed to distort the geometry of the host to wrap C60 .

Lanthanide Complexes of DO3A-(Dibenzylamino)methylphosphinate: Effect of Protonation of the Dibenzylamino Group on the Water-Exchange Rate and the Binding of Human Serum Albumin.

Protonation of a distant, noncoordinated group of metal-based magnetic resonance imaging contrast agents potentially changes their relaxivity. The effect of a positive charge of the drug on the human serum albumin (HSA)-drug interaction remains poorly understood as well. Accordingly, a (dibenzylamino)methylphosphinate derivative of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was efficiently synthesized using pyridine as the solvent for a Mannich-type reaction of tBu3DO3A, formaldehyde, and Bn2NCH2PO2H2 ethyl ester. The ligand protonation and metal ion (Gd3+, Cu2+, and Zn2+) stability constants were similar to those of the parent DOTA, whereas the basicity of the side-chain amino group of the complexes (log KA = 5.8) was 1 order of magnitude lower than that of the free ligand (log KA = 6.8). The presence of one bound water molecule in both deprotonated and protonated forms of the gadolinium(III) complex was deduced from the solid-state X-ray diffraction data [gadolinium(III) and dysprosium(III)], from the square antiprism/twisted square antiprism (SA/TSA) isomer ratio along the lanthanide series, from the fluorescence data of the europium(III) complex, and from the 17O NMR measurements of the dysprosium(III) and gadolinium(III) complexes. In the gadolinium(III) complex with the deprotonated amino group, water exchange is extremely fast (τM = 6 ns at 25 °C), most likely thanks to the high abundance of the TSA isomer and to the presence of a proximate protonable group, which assists the water-exchange process. The interaction between lanthanide(III) complexes and HSA is pH-dependent, and the deprotonated form is bound much more efficaciously (∼13% and ∼70% bound complex at pH = 4 and 7, respectively). The relaxivities of the complex and its HSA adduct are also pH-dependent, and the latter is approximately 2-3 times increased at pH = 4-7. The relaxivity for the supramolecular HSA-complex adduct ( r1b) is as high as 52 mM-1 s-1 at neutral pH (at 20 MHz and 25 °C). The findings of this study stand as a proof-of-concept, showing the ability to manipulate an albumin-drug interaction, and thus the blood pool residence time of the drug, by introducing a positive charge in a side-chain amino group.

The Phenanthridine-modified Tyrosine Dipeptide

Dipeptide 4 containing two unnatural amino acids, a modified tyrosine and a phenanthridine derivative, was synthesized. Binding of the dipeptide to a series of polynucleotides including ct-DNA, poly A - poly U, poly (dAdT)2, poly dG - poly dC and poly (dGdC)2 was investigated by thermal denaturation experiments, fluorescence spectroscopy and circular dichroism. Thermal denaturation experiments indicated that dipeptide 4 at pH 5.0, when phenanthridine is protonated, stabilizes ds-DNA, whereas it destabilizes ds-RNA. At pH 7.0, when the phenanthridine is not protonated, effects of 4 to the polynucleotide melting temperatures are negligible. At pH 5.0, dipeptide 4 stabilized DNA double helices, and the changes in the CD spectra suggest different modes of binding to ds-DNA, most likely the intercalation to poly dG- poly dC and non-specific binding in grooves of other DNA polynucleotides. At variance to ds-DNA, addition of 4 destabilized ds-RNA against thermal denaturation and CD results suggest that addition of 4 probably induced dissociation of ds-RNA into ss-RNA strands due to preferred binding to ss-RNA. Thus, 4 is among very rare small molecules that stabilize ds-DNA but destabilize ds-RNA. However, fluorescence titrations with all polynucleotides at both pH values gave similar binding affinity (log Ka ≈ 5), indicating nonselective binding. Preliminary photochemical experiments suggest that dipeptide 4 reacts in the photochemical reaction, which affects polynucleotides chirality, presumably via quinone methide intermediates that alkylate DNA.

Recognition and Binding of Aliphatic Dicarboxylic Acids C4 – C10 by Diiminocalix[4]arene

Host-Guest complexation of 5,17-bis-(N-tolyliminomethyl)-25,27-dipropoxycalix[4]arenewithaliphatic dicarboxylicacidsC4 – C10 hasbeenstudiedin water-organic solution by the RP HPLC and molecular modeling methods. The stability constants (log KA =2.56– 3.05) of the supramolecular complexes are depended on structure, pKa and log Pvalues of the acids. The complexation is determined by the hydrogen bonds of the COOH group of the dicarboxylic acids with nitrogen atoms at the upper rim or oxygen atoms at the lower rim of the calixarene.

(Invited) Complexation and Electronic Communication of Corannulene-Based Buckybowls and a Curved Electron Donor

Polycyclic aromatic hydrocarbons (PAHs) represent a large family of molecular building blocks based on multiple fused aromatic rings. The fact that the concave and convex surfaces of buckybowls, on one hand, and their edges, on the other hand, are readily available for reactions offers intriguing possibilities in chemistry. Buckybowls have been targeted as molecular building blocks toward more complex carbon nanoforms such as carbon nanotubes.1 Finally, and most importantly, buckybowls show unique electronic properties, often in between those of flat PAHs and fullerenes, which can be skillfully exploited for organic electronics applications. With regard to supramolecular chemistry, buckybowls have been studied thoroughly as hosts for fullerenes owing to their shape complementarity. However, the association of buckybowls by other organic hosts has hardly been investigated. Recently, we described the association of a fullerene fragment, hemifullerene C30H12, by an electron-donating, bowl-shaped tetrathiafulvalene derivative (truxTTF), in which three 1,3-dithiole rings are attached to a truxene core.2 The stability of the associate was remarkable, with an association constant of log Ka = 3.6±0.3 in CHCl3 at room temperature. Moreover, we demonstrated photoinduced electron transfer from truxTTF to C30H12 to form the fully charge-separated species, which constituted the first example in which a buckybowl mimicked the electron-accepting properties of fullerenes within supramolecular complexes.2 In contrast to hemifullerene C30H12, the recently reported larger C32H12 and C38H14 buckybowls are corannulene-based fragments of [60] and [70]fullerene, respectively. Such a difference in core aromatic structure is likely to be accompanied by fundamental differences in electronic properties. Here, we demonstrate that truxTTF forms heteromolecular associates with C32H12 and C38H14 in a variety of organic solvents.3 Density functional theory (DFT) calculations showed several different approximations of the heteromolecular complexes, all with favorable interaction energies, but only one, that is, the staggered arrangement, with a significant negative free energy of complexation. NMR experiments confirmed the formation of staggered structures for both heterodimers in solution. Spectroelectrochemical and transient absorption studies revealed that photoinduced electron transfer (PET) occurs in truxTTF·C38H14, thus showing that corannulene p-extended derivatives resemble the electronic behavior of [60]fullerene. References a) U. H. F. Bunz, S. Menning, N. Martín, "para-Connected Cyclophenylenes and Hemispherical Polyarenes: Building Blocks for Single Walled Carbon Nanotubes?" Angew. Chem. Int. Ed., 2012, 51, 7094-7101; b) E. M. Pérez, N. Martín, " π–π interactions in carbon nanostructures" Chem. Soc. Rev., 2015, 44, 6425-6433.M. Gallego, J. Calbo, J. Aragó, R. M. Krick Calderon, F. H. Liquido, T. Iwamoto, A. K. Greene, E. A. Jackson, E. M. Pérez, E. Ortí, D. M. Guldi, L. T. Scott, N. Martín, Angew. Chem. Int. Ed., 2014, 53, 2170-2175.M. Gallego, J. Calbo, R. M. Krick Calderon, P. Pla, Y. Hsieh, E. M. Pérez, Y. Wu, E. Ortí, D. M. Guldi, N. Martín, Chem. Eur. J. 2017, 23, 3666-3673.