Aiding a Better Understanding of Molybdopterin: Syntheses, Structures, and pKa Value Determinations of Varied Pterin-Derived Organic Scaffolds Including Oxygen, Sulfur and Phosphorus Bearing Substituents

Compounds from the 2,2’-bipyridine molecular family were investigated for use as redox-active materials in organic flow batteries. For 156 2,2’-bipyridine derivatives reported in the academic literature, we calculated the redox potential, the pKa for the first protonation reaction, and the solubility in aqueous solutions. Using experimental data on a small subset of derivatives, we were able to calibrate our calculations. We find that functionalization with electron-withdrawing groups leads to an increase of the redox potential and to an increase of the molecular acidity (as expressed in a reduction of the pKa value for the first protonation step). Furthermore, calculations of solubility in water indicate that some of the studied derivatives have adequate solubility for flow battery applications. Based on an analysis of the physico-chemical properties of the 156 studied compounds, we down-select five molecules with carbonyl- and nitro-based functional groups, whose parameters are especially promising for potential application as negative redox-active material inorganic flow batteries.

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Theoretical Exploration of 2,2’-Bipyridines as Electro-Active Compounds in Flow Batteries

10.26434/chemrxiv.7995935 ◽

2019 ◽

Author(s):

Mariano Sánchez-Castellanos ◽

Martha M. Flores-Leonar ◽

Zaahel Mata-Pinzón ◽

Humberto G. Laguna ◽

Karl García-Ruiz ◽

...

Keyword(s):

Redox Potential ◽

Active Material ◽

Chemical Properties ◽

Small Subset ◽

Solubility In Water ◽

Protonation Reaction ◽

Redox Active ◽

Physico Chemical ◽

Pka Value ◽

Flow Batteries

Compounds from the 2,2’-bipyridine molecular family were investigated for use as redox-active materials in organic flow batteries. For 156 2,2’-bipyridine derivatives reported in the academic literature, we calculated the redox potential, the pKa for the first protonation reaction, and the solubility in aqueous solutions. Using experimental data on a small subset of derivatives, we were able to calibrate our calculations. We find that functionalization with electron-withdrawing groups leads to an increase of the redox potential and to an increase of the molecular acidity (as expressed in a reduction of the pKa value for the first protonation step). Furthermore, calculations of solubility in water indicate that some of the studied derivatives have adequate solubility for flow battery applications. Based on an analysis of the physico-chemical properties of the 156 studied compounds, we down-select five molecules with carbonyl- and nitro-based functional groups, whose parameters are especially promising for potential application as negative redox-active material inorganic flow batteries.

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Dissociation of imino proton(s) of a highly water-soluble metal-free phthalocyanine and determination of its pKa value in water

Journal of Porphyrins and Phthalocyanines ◽

10.1142/s1088424613500235 ◽

2013 ◽

Vol 17 (06n07) ◽

pp. 447-453 ◽

Cited By ~ 2

Author(s):

Hiroaki Isago ◽

Harumi Fujita

Keyword(s):

Aqueous Media ◽

Thermal Reaction ◽

Water Soluble ◽

Acid Dissociation ◽

Acid Dissociation Constant ◽

Metal Free ◽

Imino Proton ◽

Pka Value ◽

Triton X

Dissociation of imino proton(s) in the cavity of the macrocycle of a highly water-soluble, metal-free phthalocyanine ( H 2( H 4 tsppc ); where H 4 tsppc denotes tetrakis{(2′,6′-dimethyl-4′-sulfonic acid)phenoxy}phthalocyaninate) in ethanolic and aqueous solutions has spectrophotometrically been investigated. The spectral changes associated with reaction with NaOH have been found to involve one-proton transfer process in aqueous media while two-protons process in ethanolic media. The acid-dissociation constant of the first imino proton in water (in the presence of Triton X-100) has been determined to be 12.5 ± 0.2 (as pKa) at 25 °C. The doubly deprotonated species in EtOH has been easily converted to its corresponding cobalt(II) derivative by thermal reaction with anhydrous CoCl 2.

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Probing the ionization state of substrate α-d-glucopyranosyl phosphate bound to glycogen phosphorylase b

Biochemical Journal ◽

10.1042/bj3081017 ◽

1995 ◽

Vol 308 (3) ◽

pp. 1017-1023 ◽

Cited By ~ 1

Author(s):

I P Street ◽

S G Withers

Keyword(s):

Active Site ◽

Glycogen Phosphorylase ◽

Ph Dependence ◽

Substrate Inhibition ◽

19F Nmr ◽

Ionization State ◽

Nmr Studies ◽

Substrate Analogues ◽

Glycogen Phosphorylase B ◽

Pka Value

The ionization state of the substrate alpha-D-glucopyranosyl phosphate bound at the active site of glycogen phosphorylase has been probed by a number of techniques. Values of Ki determined for a series of substrate analogue inhibitors in which the phosphate moiety bears differing charges suggest that the enzyme will bind both the monoanionic and dianionic substrates with approximately equal affinity. These results are strongly supported by 31P- and 19F-NMR studies of the bound substrate analogues alpha-D-glucopyranosyl 1-methylenephosphonate and 2-deoxy-2-fluoro-alpha-D-glucopyranosyl phosphate, which also suggest that the substrate can be bound in either ionization state. The pH-dependences of the inhibition constants K1 for these two analogues, which have substantially different phosphate pK2 values (7.3 and 5.9 respectively), are found to be essentially identical with the pH-dependence of K(m) values for the substrate, inhibition decreasing according to an apparent pKa value of 7.2. This again indicates that there is no specificity for monoanion or dianion binding and also reveals that binding is associated with the uptake of a proton. As the bound substrate is not protonated, this proton must be taken up by the proton.

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Derivatives of isatin in aqueous solution. I. Kinetics of ring opening of Isatin-5-sulfonate

Australian Journal of Chemistry ◽

10.1071/ch9810365 ◽

1981 ◽

Vol 34 (2) ◽

pp. 365 ◽

Cited By ~ 7

Author(s):

H Stunzi

Keyword(s):

Ring Opening ◽

Rate Of Change ◽

Spectroscopic Methods ◽

Ph Values ◽

Buffer Region ◽

Pka Value ◽

Back Titration ◽

Kinetics Of ◽

Derivatives Of ◽

Sulfonate Anion

The reactions of isatin-5-sulfonate anion (si-) which cause a hysteresis in pH titrations were studied by pH-metric and n.m.r, spectroscopic methods. Rapid alkalimetric titrations [I 0.15 M (KNO3),37�] gave the pKa value corresponding to the addition of OH- to si- [pKa(ring) 9.55]. The slow ring opening to the sulfonatoisatate dianion (sia2-) led to a drift of the pH values towards an equilibrium buffer region. Its pKa, value [pKa(eq) 3.44] corresponds to the reaction si-+H2O ↔ sia 2-+H+ Rapid back-titration gave the pKa value of the ring-opened species Hsia- [pKa(open) c. 1.3]. The rate law for the ring opening d[sia]/dt=k2 [siOH](OH)+k1*[si] was obtained from the rate of change of pH. N-Methylisatin-5-sulfonate behaves analogously.

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Ionization characteristics of the Cys-25/His-159 interactive system and of the modulatory group of papain: resolution of ambiguity by electronic perturbation of the quasi-2-mercaptopyridine leaving group in a new pyrimidyl disulphide reactivity probe

Biochemical Journal ◽

10.1042/bj2900289 ◽

1993 ◽

Vol 290 (1) ◽

pp. 289-296 ◽

Cited By ~ 22

Author(s):

G W Mellor ◽

E W Thomas ◽

C M Topham ◽

K Brocklehurst

Keyword(s):

Ph Dependence ◽

Order Rate Constant ◽

Ion Pair ◽

Catalytic Site ◽

Alkaline Media ◽

Interactive System ◽

Data Set ◽

Pka Value ◽

Compound Ii ◽

Pair State

1. A new thiol-specific reactivity probe 4,4′-dipyrimidyl disulphide [compound (VII), m.p. 110 degrees C, pKa of its monohydronated form 0.91] was synthesized and used to resolve the ambiguity of interpretation of the behaviour of papain (EC 3.4.22.2) in alkaline media known to depend to varying extents on two ionizations with pKa values approx. 8.0-8.5 and > or = 9.5 respectively. 2. A new extensive pH-second-order rate constant (k) data set for the reaction of papain with 2-(acetamido)-ethyl 2′-pyridyl disulphide (IV) demonstrated the existence of a striking rate maximum at pH approx. 4, the independence of k around pH 8 and the increase in k with increase in pH across a pKa value of 10.0, behaviour similar to that of other 2-pyridyl disulphides (R-S-S-2-Py) that lack key substrate-like binding sites in R. 3. Although the simplest interpretation of the pKa value of 10.0 assigns it to the formation of (Cys-25)-S-/(His-159)-Im from the ion-pair state of the papain catalytic site, another interpretation may be conceived in which this pKa value is assigned to another group remote from the catalytic site, the state of ionization of which modulates catalytic-site behaviour. This alternative assignment is shown to require compensating effects in the pH region around 8 such that the formation of (Cys-25)-S-/(His-159)-Im across pKa 8.0-8.5 is without net kinetic effect in the reactions of simple 2-pyridyl disulphides such as compound (IV) and 2,2′-dipyridyl disulphide (II). 4. The lower basicity of compound (VII) relative to that of compound (II) (pKa 2.45) was predicted to diminish or abolish the compensation postulated as a possibility in reactions of 2-pyridyl disulphides because of the decreased effectiveness of reaction via a (His-159)-Im+H-assisted transition state. The characteristics of the pH-dependence of the reaction of papain with compound (VII) which are quite different from those for its reaction with compound (II) support both this prediction and the alternative assignment with a value of 8.3 for the pKa of the formation of (Cys-25)-S-/(His-159)-Im. 5. Evidence that the behaviour of papain towards both substrates and some substrate-derived time-dependent inhibitors is determined not only by the loss of the (Cys-25)-S-/(His-159)-Im+H ion-pair state by dehydronation with pKa 8.3 but also by another ionization of pKa approx. 10.0 is briefly discussed.

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The pKa value of the proximal water molecule trans to a high-valent MnVO porphyrin: towards the control of reactivity by pH

Dalton Transactions ◽

10.1039/c7dt01829k ◽

2017 ◽

Vol 46 (36) ◽

pp. 12088-12094 ◽

Cited By ~ 1

Author(s):

Laurie Saint-Germes ◽

Laure Bar ◽

Jérôme Dejeu ◽

Nicolas Spinelli ◽

Eric Defrancq ◽

...

Keyword(s):

Water Molecule ◽

Hydroxyl Group ◽

Protonation State ◽

Pka Value ◽

High Valent

In water, the protonation state of the proximal water molecule of a high-valent manganese-oxo porphyrin could be controlled by pH. While in interaction with DNA the porphyrin was able to cleave DNA, only when the proximal water molecule was in the form of a hydroxyl group.

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Computer programs for calculating pKa: A comparative study for 3-[3-(2-nitrophenyl)prop-2-enoyl]-2h-1-benzopyran-2-one

Journal of the Serbian Chemical Society ◽

10.2298/jsc1002243s ◽

2010 ◽

Vol 75 (2) ◽

pp. 243-248 ◽

Cited By ~ 1

Author(s):

Selma Spirtovic-Halilovic ◽

Davorka Zavrsnik

Keyword(s):

Antimicrobial Activity ◽

Computer Program ◽

Dissociation Constant ◽

Chemical Compounds ◽

Computer Programs ◽

Good Activity ◽

Target Compound ◽

Theoretical Approaches ◽

Pka Value ◽

Good Agreement

Coumarin-based compounds containing a chalcone moiety exhibit antimicrobial activity. These substances are potential drugs and it is important to determine their pKa values. However, they are almost insoluble in water. The dissociation constant was experimentally determined by potentiometric titration for 3-[3-(2-nitrophenyl)prop-2-enoyl]-2H-1-benzopyran-2-one because this compound shows good activity and solubility. A number of different computer programs for the calculation of the dissociation constant of chemical compounds have been developed. The pKa value of the target compound was calculated using three different computer programs, i.e., the ACD/pKa, CSpKaPredictor and ADME/ToxWEB programs, which are based on different theoretical approaches. The analysis demonstrated good agreement between the experimentally observed pKa value of 3-[3-(2-nitrophenyl)prop-2-enoyl]-2H-1-benzopyran- 2-one and the value calculated using the computer program CSpKa.

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The pKa of the catalytic histidine residue of chloramphenicol acetyltransferase

Biochemical Journal ◽

10.1042/bj2900015 ◽

1993 ◽

Vol 290 (1) ◽

pp. 15-19 ◽

Cited By ~ 7

Author(s):

A Lewendon ◽

W V Shaw

Keyword(s):

Chemical Modification ◽

Ph Dependence ◽

Thiol Group ◽

Chloramphenicol Acetyltransferase ◽

Histidine Residue ◽

Pka Values ◽

Primary Hydroxy Group ◽

Pka Value ◽

Catalytic Role ◽

Kinetics Of

A catalytically essential histidine residue (His-195) of chloramphenicol acetyltransferase (CAT) acts as a general base in catalysis, abstracting a proton from the primary hydroxy group of chloramphenicol. The pKa of His-195 has been determined from the pH-dependence of chemical modification. Both methyl 4-nitrobenzenesulphonate and iodoacetamide inactivate CAT by irreversible modification of His-195. The kinetics of inactivation by methyl 4-nitrobenzenesulphonate are pseudo-first-order, and the pH-dependence of inactivation yields a pKa value of 6.60. Iodoacetamide inactivation proceeds with second-order kinetics and a pKa value of 6.80. An alternative site of modification at the active site of CAT is the thiol group of Cys-31, a residue which has no catalytic role. On replacement of Cys-31 with alanine (Ala-31 CAT), the pH-dependence of iodoacetamide inactivation gives a pKa value of 6.66. The pKa values derived from chemical-modification experiments directed at His-195 are in agreement with the pKa values of 6.62 and 6.61 determined for wild-type and Ala-31 CAT respectively from the pH-dependence of kcat/Km.

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A fluorescent pH probe for an aqueous solution composed of 7-hydroxycoumarin, Schiff base and phenanthro[9,10-d]imidazole moieties (PICO)

Heterocyclic Communications ◽

10.1515/hc-2017-0174 ◽

2018 ◽

Vol 24 (2) ◽

pp. 93-97

Author(s):

Shaoxin Li ◽

Wei Kan ◽

Bing Zhao ◽

Ting Liu ◽

Yue Fang ◽

...

Keyword(s):

Aqueous Solution ◽

Schiff Base ◽

Fluorescent Probe ◽

Fluorescence Intensity ◽

Ph Probe ◽

Pka Value

AbstractThe pH fluorescent probe 7-hydroxy-4-methyl-8-(((2-(1-phenyl-1H-phenanthro[9,10-d]imidazol-2-yl)phenyl)imino)methyl)-2H-chromen-2-one (PICO) contains a donor–π–acceptor (D–π–A) conjugated system. The ‘off−on’ probe PICO has a pKa value of 8.01 and its fluorescence intensity is enhanced with increasing pH.

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