Oxidation,Redox Disproportionation and Chain Termination Reactions Catalysed by the Pd‐561 Giant Cluster

Redox disproportionation of benzyl alcohol to benzaldehyde and toluene catalysed by the Pd₅₆₁phen₆₀(OAc)₁₈₀ (phen=1,10‐phenanthroline) giant cluster 1 under anaerobic conditions was found, whereas in an O₂ atmosphere cluster 1 catalyses the oxidation of benzyl alcohol to benzaldehyde and inhibits further oxidation of the latter. A study of the AIBN‐initiated and non‐initiated oxidation of benzyl alcohol, sec‐butyl alcohol and styrene in the presence of cluster 1 revealed that cluster 1 performs three functions in the oxidation reactions: 1) catalysis of polar oxidation of the substrates with O₂, 2) termination of the chains of radical oxidation, and 3) catalysis of redox disproportionation.     

Cobalt(II) Phthalocyanine‐Catalyzed Highly Chemoselective Reductive Amination of Carbonyl Compounds in a Green Solvent

Cobalt phthalocyanine has been employed for the highly chemoselective reductive amination of aldehydes and ketones in ethanol as a green solvent. A large range of functional groups such as nitro, acid, amide, ester, nitrile, halogen, lactone, methoxy, hydroxy, alkene, N‐benzyl, O‐benzyl and heterocyclic rings were well tolerated under the present reaction conditions.     

Multivalent Display and Receptor‐Mediated Endocytosis of Transferrin on Virus‐Like Particles

The structurally regular and stable self‐assembled capsids derived from viruses can be used as scaffolds for the display of multiple copies of cell‐ and tissue‐targeting molecules and therapeutic agents in a convenient and well‐defined manner. The human iron‐transfer protein transferrin, a high affinity ligand for receptors upregulated in a variety of cancers, has been arrayed on the exterior surface of the protein capsid of bacteriophage Qβ. Selective oxidation of the sialic acid residues on the glycan chains of transferrin was followed by introduction of a terminal alkyne functionality through an oxime linkage. Attachment of the protein to azide‐functionalized Qβ capsid particles in an orientation allowing access to the receptor binding site was accomplished by the Cu^I‐catalyzed azide–alkyne cycloaddition (CuAAC) click reaction. Transferrin conjugation to Qβ particles allowed specific recognition by transferrin receptors and cellular internalization through clathrin‐mediated endocytosis, as determined by fluorescence microscopy on cells expressing GFP‐labeled clathrin light chains. By testing Qβ particles bearing different numbers of transferrin molecules, it was demonstrated that cellular uptake was proportional to ligand density, but that internalization was inhibited by equivalent concentrations of free transferrin. These results suggest that cell targeting with transferrin can be improved by local concentration (avidity) effects.     

Direct Arylation of Thiophenes via Palladium‐Catalysed C?H Functionalisation at Low Catalyst Loadings

Palladium associated with cis,cis,cis‐1,2,3,4‐tetrakis(diphenylphosphinomethyl)cyclopentane (Tedicyp) was found to promote the direct 2‐arylation of a variety of thiophene derivatives via C H functionalisation in good yields using very low catalyst loadings. Electron‐deficient, electron‐excessive or sterically‐congested aryl bromides are tolerated. Moreover, several substituents on the aryl bromide or thiophene derivatives such as acetyl, formyl, nitrile, nitro, ester, methoxy, fluoro or trifluoromethyl are tolerated. The most reactive aryl bromides were coupled with thiophenes derivatives using as little as 0.1–0.01 mol % catalyst.     

A Single Mutation Increases the Activity and Stability of Pectobacterium carotovorum Nitrile Reductase

Nitrile reductases are considered to be promising and environmentally benign nitrile‐reducing biocatalysts to replace traditional metal catalysts. Unfortunately, the catalytic efficiencies of the nitrile reductases reported so far are very low. To date, all attempts to increase the catalytic activity of nitrile reductases by protein engineering have failed. In this work, we successfully increased the specific activity of a nitrile reductase from Pectobacterium carotovorum from 354 to 526 U g_prot^?1 by engineering the substrate binding pocket; moreover, the thermostability was also improved (≈2‐fold), showing half‐lives of 140 and 32 h at 30 and 40 °C, respectively. In the bioreduction of 2‐amino‐5‐cyanopyrrolo[2,3‐d]pyrimidin‐4‐one (preQ₀) to 2‐amino‐5‐aminomethylpyrrolo[2,3‐d]pyrimidin‐4‐one (preQ₁), the variant was advantageous over the wild‐type enzyme with a higher reaction rate and complete conversion of the substrate within a shorter period. Homology modeling and docking analysis revealed some possible origins of the increased activity and stability. These results establish a solid basis for future engineering of nitrile reductases to increase the catalytic efficiency further, which is a prerequisite for applying these novel biocatalysts in synthetic chemistry.     

Design of Cyclic Peptides Featuring Proline Predominantly in the cis Conformation under Physiological Conditions

Turns are secondary‐structure elements that are omnipresent in natively folded polypeptide chains. A large variety of four‐residue β‐turns exist, which differ mainly in the backbone dihedral angle values of the two central residues i+1 and i+2. The βVI‐type turns are of particular biological interest because the i+2 residue is always a proline in the cis conformation and might thus serve as target of peptidyl prolyl cis/trans isomerases (PPIases). We have designed cyclic hexapeptides containing two proline residues that predominantly adopt the cis conformation in aqueous solution. NMR data and MD calculations indicated that the cyclic peptide sequences c‐(‐D Xaa‐Ser‐Pro‐D Xaa‐Lys‐Pro‐) result in highly symmetric backbone structures when both prolines are in the cis conformation and the D ‐amino acids are either alanine or phenylalanine residues. Replacement of the serine residue either by phosphoserine or by tyrosine compromises this symmetry, but further increases the cis conformation content of both prolines. As a result, we obtained a cyclic hexapeptide that exists almost exclusively as the cis‐Pro/cis‐Pro conformer but shows no cis/trans interconversion even in the presence of the PPIase Pin1, apparently due to an energetically quite favorable but highly restricted conformational space.     

Fe(PyTACN)‐Catalyzed cis‐Dihydroxylation of Olefins with Hydrogen Peroxide

A family of iron complexes with general formula [Fe(II)(^R,Y,XPyTACN)(CF₃SO₃)₂], where ^R,Y,XPyTACN=1‐[2′‐(4‐Y‐6‐X‐pyridyl)methyl]‐4,7‐dialkyl‐1,4,7‐triazacyclononane, X and Y refer to the groups at positions 4 and 6 of the pyridine, respectively, and R refers to the alkyl substitution at N‐4 and N‐7 of the triazacyclononane ring, are shown to be catalysts for efficient and selective alkene oxidation (epoxidation and cis‐dihydroxylation) employing hydrogen peroxide as oxidant. Complex [Fe(II)(^Me,Me,HPyTACN)(CF₃SO₃)₂] ( 7 ), was identified as the most efficient and selective cis‐dihydroxylation catalyst among the family. The high activity of 7 allows the oxidation of alkenes to proceed rapidly (30 min) at room temperature and under conditions where the olefin is not used in large amounts but instead is the limiting reagent. In the presence of 3 mol% of 7 , 2 equiv. of H₂O₂ as oxidant and 15 equiv. of water, in acetonitrile solution, alkenes are cis‐dihydroxylated reaching yields that might be interesting for synthetic purposes. Competition experiments show that 7 exhibits preferential selectivity towards the oxidation of cis olefins over the trans analogues, and also affords better yields and high [syn‐diol]/[epoxide] ratios when cis olefins are oxidized. For aliphatic substrates, reaction yields attained with the present system compare favourably with state of the art Fe‐catalyzed cis‐dihydroxylation systems, and it can be regarded as an attractive complement to the iron and manganese systems described recently and which show optimum activity against electron‐deficient and aromatic olefins.     

Chemical Characterization of a High‐Oleic Soybean Oil

High‐oleic low‐linolenic acid soybean oil (HOLLSB, Plenish^®) is an emerging new oil with projections of rapid expansion in the USA. HOLLSB has important technological advantages, which are expected to drive a gradual replacement of commodity oils used in food applications such as soybean oil. A key technological advantage of HOLLSB is its relatively high oxidation stability. This oxidation stability is the result of a favorable fatty acid composition, high (76%) oleic acid, low linoleic (6.7%), and alpha‐linolenic (1.6%) acids, and high concentration of tocopherols (936 ppm) after refining, enriched with the gamma‐homolog (586 ppm). A detailed analysis of the fatty acid composition of this HOLLSB by gas chromatography–mass spectrometry allowed the identification and structural determination of 9‐cis‐heptadecenoic acid (or 17:1n‐8). To our knowledge, this is the first time 9‐cis‐heptadecenoic acid has been unequivocally reported in soybean oil. This unusual fatty acid component has the potential to be used as a single authenticity marker for the quantitative assessment of soybean oil. The Rancimat induction period (IP) of Plenish^® (16.1 hours) was higher than those of other commercially available high‐oleic oils, such as canola (13.4 hours), and Vistive^® Gold (10 hours), a different variety of soybean oil. Plenish^® showed the same IP as high‐oleic sunflower oil. Plenish^® shows a modest increase in oxidation stability with the external addition or relatively high concentrations of tocopherols. The characteristic high oxidative stability of Plenish^® may be further enhanced with the use of nontocopherol antioxidants.     

Fine‐Tunable Tris(triazolyl)methane Ligands for Copper(I)‐ Catalyzed Azide–Alkyne Cycloaddition Reactions

The preparation of a small library of modular tris(triazolyl)methane ligands for copper‐catalyzed azide–alkyne cycloaddition (CuAAC) reactions is reported. The synthesis of the first generation ligand, tris(1‐benzyl‐1H‐1,2,3‐triazol‐4‐yl)methanol ( 1a ), suitable for work in aqueous systems, is reported at the 50–100 mmol scale through a one‐stage, environmentally benign procedure. One‐stage procedures for the synthesis of tris(aryltriazolyl)methanol structures ( 1b , phenyl; 1c , para‐trifluoromethylphenyl; 1d , para‐methoxyphenyl) designed for electronic fine‐tuning of catalytic properties, and of 1a ‐derived ethers 2c (OBn) and 2d (OMe), designed for CuAAC reactions in organic solvents, are also reported. The complete set of ligands ( 1a–d , 2c–d ) has been tested in the reaction of phenylacetylene with benzyl azide in six different solvents (water, hexane, toluene, dichloromethane, tetrahydrofuran, and acetonitrile), and this has allowed the identification of 1b , 1c and 2c as the ligands depicting the highest tolerance to changes in solvent polarity within the considered family. The comparative performance of ligands 1b–d and 2c in the cycloaddition of a small family of alkynes with benzyl azide in two very different reaction media (1:1 t‐BuOH/H₂O and toluene) has been studied as a guide for catalyst selection in specific applications. The applicability of 1c in CuAAC reactions involving functional substrates in toluene has been explored under thermal and microwave‐accelerated (tandem azide formation plus CuAAC reaction) reaction conditions.

     

TEMPO‐Copper(II) Diimine‐Catalysed Oxidation of Benzylic Alcohols in Aqueous Media

In situ generated copper(II)‐diimine complexes combined with TEMPO (2,2,6,6‐tetramethylpiperidinyl‐1‐oxyl radical) were studied in the oxidation of benzylic alcohols, the focus being on enviromentally benign reaction conditions. In this respect, reactions were studied in aqueous alkaline solutions and dioxygen was used as an end oxidant. This simple catalytic system turned out to be highly efficient and selective in the oxidation of primary and secondary benzylic alcohols to their corresponding carbonyl compounds. Under optimised reaction conditions [5 mol % of TEMPO, 3 mol % of copper(II ) diimine, pH 12.6–13.5, 80 °C, 10 bar O₂] benzyl alcohol was quantitatively and selectively oxidised to benzaldehyde. According to ESI‐MS studies, coordination of TEMPO, as well as deprotonated benzyl alcohol to the parent copper‐diimine complex in aqueous solutions is feasible. Supported by these observations a plausible reaction mechanism is proposed for the oxidation reaction.     

Synthesis and characterization of novel aromatic ether nitrile monomer containing propenylphenoxy groups and properties of its copolymer with 4,4′‐bismaleimidodiphenylmethane

A novel aromatic ether nitrile monomer containing propenyl groups, 2,6‐di{2‐[(E)‐1‐propenyl]phenoxy} benzonitrile (DPPB), was synthesized by the reaction of 2,6‐dichlorobenzonitrile and 2‐allylphenol using anhydrous potassium carbonate as the acid acceptor, N‐methyl pyrrolidone as the dipolar aprotic solvent, and toluene as the dehydrating agent. The chemical structure of DPPB was characterized by FTIR and ¹H‐NMR. The monomer was used to modify a popular commercial bismaleimide, 4,4‐bismaleimidodiphenylmethane (BMDPM), to improve the shear strength of the resin. The results showed that DPPB could effectively improve the shear strength of the BMDPM resin without decreasing the heat resistance of BMDPM. A better result was obtained when the composition of DPPB in the copolymer was 45 wt %. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 83: 1465–1472, 2002     

Liquid‐Phase Aerobic Oxidation of Benzyl Alcohol Catalyzed by Pt/ZrO2

The oxidation of benzyl alcohol by molecular oxygen in the liquid phase and catalyzed by Pt/ZrO2 using n‐heptane as the solvent was studied. Pt/ZrO₂ was very active and 100 % selective for benzyl alcohol conversion to benzaldehyde. The catalyst can be separated by filtration and reused. No leaching of Pt or Zr into the solution was observed. Typical batch reactor kinetic data were obtained and fitted to the Langmuir‐Hinshelwood, Eley‐Rideal and Mars‐van Krevelen models of heterogeneously catalyzed reactions. The Langmuir‐Hinshelwood model was found to give a better fit. The rate‐determining step was proposed to involve direct interaction of an adsorbed oxidizing species with the adsorbed reactant or an intermediate product of the reactant. H₂O₂ was also proposed to be an intermediate product. n‐Heptane was found to be an appropriate solvent in this reaction system.     

Synthesis and characterization of polyamides and poly(amide‐imide)s derived from 2,6‐bis(3‐aminophenoxy)benzonitrile or 2,6‐bis(4‐aminophenoxy)benzonitrile

A series of polyamides and poly(amide‐imide)s was prepared by direct polycondensation of ether and nitrile group containing aromatic diamines with aromatic dicarboxylic acids and bis(carboxyphthalimide)s respectively in N‐methyl 2‐pyrrolidone (NMP) using triphenyl phosphite and pyridine as condensing agents. New diamines, such as 2,6‐bis(4‐aminophenoxy)benzonitrile and 2,6‐bis(3‐aminophenoxy)benzonitrile, were prepared from 2,6‐dichlorobenzonitrile with 4‐aminophenol and 3‐aminophenol, respectively, in NMP using potassium carbonate. Bis(carboxyphthalimide)s were prepared from the reaction of trimellitic anhydride with various aromatic diamines in N,N′‐dimethyl formamide. The inherent viscosities of the resulting polymers were in the range of 0.27 to 0.93 dl g^?1 in NMP and the glass transition temperatures were between 175 and 298 °C. All polymers were soluble in dipolar aprotic solvents such as dimethylsulfoxide, dimethylacetamide and NMP. All polymers were stable up to 350 °C with a char yield of above 40 % at 900 °C in nitrogen atmosphere. All polymers were found to be amorphous except the polyamide derived from isophthalic acid and the poly(amide‐imide)s derived from diaminodiphenylether and diaminobenzophenone based bis(carboxyphthalimide)s. Copyright © 2004 Society of Chemical Industry     

Double Bond Stereochemistry Influences the Susceptibility of Short-Chain Isoprenoids and Polyprenols to Decomposition by Thermo-Oxidation

Isoprenoid alcohols are common constituents of living cells. They are usually assigned a role in the adaptation of the cell to environmental stimuli, and this process might give rise to their oxidation by reactive oxygen species. Moreover, cellular isoprenoids may also undergo various chemical modifications resulting from the physico‐chemical treatment of the tissues, e.g., heating during food processing. Susceptibility of isoprenoid alcohols to heat treatment has not been studied in detail so far. In this study, isoprenoid alcohols differing in the number of isoprene units and geometry of the double bonds, β‐citronellol, geraniol, nerol, farnesol, solanesol and Pren‐9, were subjected to thermo‐oxidation at 80 °C. Thermo‐oxidation resulted in the decomposition of the tested short‐chain isoprenoids as well as medium‐chain polyprenols with simultaneous formation of oxidized derivatives, such as hydroperoxides, monoepoxides, diepoxides and aldehydes, and possible formation of oligomeric derivatives. Oxidation products were monitored by GC‐FID, GC‐MS, ESI‐MS and spectrophotometric methods. Interestingly, nerol, a short‐chain isoprenoid with a double bond in the cis (Z) configuration, was more oxidatively stable than its trans (E) isomer, geraniol. However, the opposite effect was observed for medium‐chain polyprenols, since Pren‐9 (di‐trans‐poly‐cis‐prenol) was more susceptible to thermo‐oxidation than its all‐trans isomer, solanesol. Taken together, these results experimentally confirm that both short‐ and long‐chain polyisoprenoid alcohols are prone to thermo‐oxidation.     

A New Chiral Organosulfur Catalyst for Highly Stereoselective Synthesis of Epoxides

A new chrial organosulfide was synthesized through an unexpected Wagner–Meerwein rearrangement. This organosulfide could catalyze the epoxidation reaction of various aromatic aldehydes smoothly with benzyl bromide to give trans‐diaryl epoxides in satisfactory yields (60–84%) with excellent diastereoselectivities (trans:cis=95:5–100:0) and good to excellent enantioselectivities (86–96% ee).     

Fourier transform near‐infrared and electron spin resonance studies on the crosslinking reaction of liquid carboxylated poly(acrylonitrile‐co‐butadiene) rubber with dicumyl peroxide in dioxane

The crosslinking reaction of liquid carboxylated poly(acrylonitrile‐co‐butadiene) [or nitrile rubber (NBR); acrylonitrile = 10 wt %] with dicumyl peroxide (DCPO) was studied in dioxane by means of Fourier transform near‐infrared spectroscopy (FT‐NIR) and electron spin resonance spectroscopy (ESR). Among the three butadiene units (1,2, cis‐1,4, and trans‐1,4 units) of NBR, only the pendant vinyl group of the 1,2 unit showed an absorption at 6110 cm^?1 from the FT‐NIR examination of dioxane solutions of NBR, 1‐octene, 3,3‐dimethyl‐1‐butene, trans‐2‐octene, cis‐5‐octen‐1‐ol, poly‐cis‐1,4‐butadiene, and poly‐1,2‐butadiene. The crosslinking reaction was followed in situ in dioxane by the monitoring of the disappearance of the pendant vinyl double bond with FT‐NIR. The initial disappearance rate (R₀) of the vinyl group was expressed by R₀ = k[DCPO]^0.9[NBR]^?0.2 (120°C). The overall activation energy of the reaction was calculated to be 20.7 kcal/mol. This unusual rate equation suggests unimolecular termination due to degradative chain transfer and depressed reactivity of the vinyl group caused by crosslinking. ESR study of the reaction mixture revealed that an allyl‐type polymer radical was formed in the reaction, and its concentration increased with time and was then saturated. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 2095–2101, 2003     

Polyethylene‐supported N‐bromosuccinimide polymeric reagent for use in some oxidation reactions

We report a three‐step preparation of a polymer‐supported oxidizing reagent, polyethylene‐g‐N‐bromosuccinimide (PE‐g‐NBS), through the graft copolymerization of maleic anhydride (MAn) onto polyethylene (PE) by a photochemical method with 1% benzophenone as a photosensitizer. The postgrafting treatment of polyethylene‐g‐maleic anhydride (PE‐g‐MAn) with urea on fusion gives polyethylene‐g‐succinimide (PE‐g‐succinimide), which, on further treatment with an aqueous solution of sodium hydroxide and bromine, gives the required reagent, PE‐g‐NBS. The maximum percentage grafting (25%) was obtained with 3.57 mol of MAn and 0.5 mL of 1% benzophenone in 120 min. Fourier transform infrared spectroscopy and thermogravimetric analysis methods were used to characterize the graft copolymer PE‐g‐MAn, PE‐g‐succinimide, and the polymeric support, that is, PE‐g‐NBS. The grafted PE and the polymeric support were found to be thermally stable. The polymer‐supported N‐bromosuccinimide was used successfully for the efficient oxidation of a series of alcohols, including 2‐propanol, n‐butanol, ethylene glycol, cyclohexanol, poly(vinyl alcohol), benzoin, benzyl alcohol, and chloromycetin, to their corresponding aldehydes and ketones. The selectivity of PE‐g‐NBS toward the oxidation of secondary alcoholic groups without the disturbance of the primary alcoholic groups was reflected during the oxidation of chloromycetin. The oxidized products were characterized by Fourier transform infrared and ¹H‐NMR spectral methods. The reagent was reused for the oxidation of fresh alcohols, and it was found to oxidize them successfully, although with a little lower product yield. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Oxidation products of free polyunsaturated fatty acids in wheat varieties

Oxygenated fatty acids (oxylipins) are secondary metabolites of polyunsaturated fatty acids (PUFA). Here, we present a novel high‐performance liquid chromatograpic separation on a reversed‐phase column (RP‐HPLC) coupled with electrospray ionization‐tandem mass spectrometry (ESI‐MS/MS) for the determination of various (per)oxidation products of linoleic (cis,cis‐9,12‐octadecadienoic) acid in eight different varieties (four spring and four winter varieties) of wheat (Triticum aestivum). The procedure includes extraction of oxylipins, chromatograpic separation using a linear gradient of aqueous formic acid and acetonitrile, with subsequent identification of compounds by MS/MS. Among the identified oxylipins, leukotoxin (LTX)‐diol and its isomer (iso‐LTX‐diol) are known as potentially toxic substances. The obtained data was used further for comparison of different wheat varieties by principal component analysis (PCA). From the results of PCA, differences can be observed in the patterns of wheat varieties.     

Oxime Palladacycle‐Catalyzed Suzuki–Miyaura Alkenylation of Aryl,Heteroaryl, Benzyl,and Allyl Chlorides under Microwave Irradiation Conditions

A simple new protocol for the palladium‐catalyzed Suzuki–Miyaura cross‐coupling of organic chlorides under microwave irradiation is presented. Deactivated aryl and heteroaryl chlorides are efficiently cross‐coupled with alkenylboronic acids and potassium alkenyltrifluoroborates using the 4,4′‐dichlorobenzophenone oxime‐derived palladacycle 1b as precatalyst in 0.1 to 0.5 mol% palladium loading, tris(tert‐butyl)phosphonium tetrafluoroborate {[HP(t‐Bu)₃]BF₄} as ligand, tetra‐n‐butylammonium hydroxide as cocatalyst, and potassium carbonate as base in N,N‐dimethylformamide at 130 °C under microwave irradiation conditions. Under these conditions, styrenes, stilbenes, and alkenylarenes are obtained in good to high yields, and with high regio‐ and diastereoselectivities in only 20 min. The reported protocol is also very efficient for the regioselective alkenylation of benzyl and allyl chlorides to afford allylarenes and 1,4‐dienes.     

A partial convergence in action of methylene blue and artemisinins: antagonism with chloroquine, a reversal with verapamil, and an insight into the antimalarial activity of chloroquine

Artemisinins rapidly oxidize leucomethylene blue (LMB) to methylene blue (MB); they also oxidize dihydroflavins such as the reduced conjugates RFH₂ of riboflavin (RF), and FADH₂ of the cofactor flavin adenine dinucleotide (FAD), to the corresponding flavins. Like the artemisinins, MB oxidizes FADH₂, but unlike artemisinins, it also oxidizes NAD(P)H. Like MB, artemisinins are implicated in the perturbation of redox balance in the malaria parasite by interfering with parasite flavoenzyme disulfide reductases. The oxidation of LMB by artemisinin is inhibited by chloroquine (CQ), an inhibition that is abruptly reversed by verapamil (VP). CQ also inhibits artemisinin‐mediated oxidation of RFH₂ generated from N‐benzyl‐1,4‐dihydronicotinamide (BNAH)–RF, or FADH₂ generated from NADPH or NADPH–Fre, an effect that is also modulated by verapamil. The inhibition likely proceeds by the association of LMB or dihydroflavin with CQ, possibly involving donor–acceptor or π complexes that hinder oxidation by artemisinin. VP competitively associates with CQ, liberating LMB or dihydroflavin from their respective CQ complexes. The observations explain the antagonism between CQ–MB and CQ–artemisinins in vitro, and are reconcilable with CQ perturbing intraparasitic redox homeostasis. They further suggest that a VP–CQ complex is a means by which VP reverses CQ resistance, wherein such a complex is not accessible to the putative CQ‐resistance transporter (PfCRT).