Ortho Hydroxyl Research Articles

Design, synthesis and evaluation of new α-nucleophiles for the hydrolysis of organophosphorus nerve agents: application to the reactivation of phosphorylated acetylcholinesterase

A series of new α-nucleophiles including oximes and amidoximes have been synthesized, and their ability to efficiently and selectively cleave the P–S bond of organophosphorus nerve agents has been evaluated. The relationship between the chemical structure of the α-nucleophiles and their reactivity towards PhX hydrolysis is reported. A significant effect induced by an ortho-hydroxyl group of aryl- and pyridyl-oximes, amidoximes on their organo-phosphono-thioase reactivity was discovered. The evaluation of the initial rates of PhX hydrolysis reaction in the presence of α-nucleophiles allowed the discovery of new uncharged molecules with increased reactivity compared to positively charged 2-pralidoxime used as antidote. The mechanism of their action was studied in details by kinetic analysis, HPLC and LC–MS methods. The most promising structures were then considered as potent in vitro reactivators of phosphylated acetylcholinesterase (AChE), which was confirmed by the preliminary results of AChE reactivation initially inhibited by VX.

Antifungal activity of redox-active benzaldehydes that target cellular antioxidation

BackgroundDisruption of cellular antioxidation systems should be an effective method for control of fungal pathogens. Such disruption can be achieved with redox-active compounds. Natural phenolic compounds can serve as potent redox cyclers that inhibit microbial growth through destabilization of cellular redox homeostasis and/or antioxidation systems. The aim of this study was to identify benzaldehydes that disrupt the fungal antioxidation system. These compounds could then function as chemosensitizing agents in concert with conventional drugs or fungicides to improve antifungal efficacy.MethodsBenzaldehydes were tested as natural antifungal agents against strains of Aspergillus fumigatus, A. flavus, A. terreus and Penicillium expansum, fungi that are causative agents of human invasive aspergillosis and/or are mycotoxigenic. The yeast Saccharomyces cerevisiae was also used as a model system for identifying gene targets of benzaldehydes. The efficacy of screened compounds as effective chemosensitizers or as antifungal agents in formulations was tested with methods outlined by the Clinical Laboratory Standards Institute (CLSI).ResultsSeveral benzaldehydes are identified having potent antifungal activity. Structure-activity analysis reveals that antifungal activity increases by the presence of an ortho-hydroxyl group in the aromatic ring. Use of deletion mutants in the oxidative stress-response pathway of S. cerevisiae (sod1Δ, sod2Δ, glr1Δ) and two mitogen-activated protein kinase (MAPK) mutants of A. fumigatus (sakAΔ, mpkCΔ), indicates antifungal activity of the benzaldehydes is through disruption of cellular antioxidation. Certain benzaldehydes, in combination with phenylpyrroles, overcome tolerance of A. fumigatus MAPK mutants to this agent and/or increase sensitivity of fungal pathogens to mitochondrial respiration inhibitory agents. Synergistic chemosensitization greatly lowers minimum inhibitory (MIC) or fungicidal (MFC) concentrations. Effective inhibition of fungal growth can also be achieved using combinations of these benzaldehydes.ConclusionsNatural benzaldehydes targeting cellular antioxidation components of fungi, such as superoxide dismutases, glutathione reductase, etc., effectively inhibit fungal growth. They possess antifungal or chemosensitizing capacity to enhance efficacy of conventional antifungal agents. Chemosensitization can reduce costs, abate resistance, and alleviate negative side effects associated with current antifungal treatments.

On-line high-performance liquid chromatography–diode array detection–electrospray ionization–mass spectrometry–chemiluminescence assay of radical scavengers in Epimedium

An on-line analysis method for the simultaneous detection and identification of radical scavenging compounds in plant extracts was developed by combining HPLC with hydrogen dioxide radical scavenging and HPLC–DAD–MS–CL system. The structural identification and activity characteristics of various constituents could be rapidly achieved by the on-line assay of UV, MS and CL in one run. In 4 species of Epimedium studied 32 compounds, including phenolic acids, 8-isopentenyl-flavonoid glycosides and flavonoid glycosides containing a ortho-hydroxyl group, were identified by comparison with authentic standards and published mass data. Among these compounds, phenolic acids and flavonoid glycosides containing an ortho-hydroxyl group could obviously inhibit CL, which suggested their strong radical scavenging activity. These four species each exhibited different active properties, which might correlate to their respective quality. The results indicated that the on-line HPLC–DAD–MS–CL system would be a potential method to rapidly and sensitively screen radical scavengers in herbal medicines, and could display an integrated fingerprint based on different detectors.

Synthesis and thermal behavior of 4,5-dihydroxyl-2-(dinitromethylene)-imidazolidine (DDNI)

A novel energetic material, 4,5-dihydroxyl-2-(dinitromethylene)-imidazolidine (DDNI), was synthesized by the reaction of FOX-7 and glyoxal in water at 70 °C. Thermal behavior of DDNI was studied with DSC and TG-DTG methods, and presents only an intense exothermic decomposition process. The apparent activation energy and pre-exponential factor of the decomposition reaction were 286.0 kJ mol−1 and 1031.16 s−1, respectively. The critical temperature of thermal explosion of DDNI is 183.78 °C. Specific heat capacity of DDNI was studied with micro-DSC method and theoretical calculation method, and the molar heat capacity is 217.76 J mol−1 K−1 at 298.15 K. The adiabatic time-to-explosion was also calculated to be a certain value between 14.54 and 16.34 s. DDNI presents lower thermal stability, for its two ortho-hydroxyl groups, and its thermal decomposition process becomes quite intense.

Aggregation and adsorption behavior of cetylpyridinium chloride in aqueous sodium salicylate and sodium benzoate solutions

The critical micelle concentration (cmc) values of cetylpyridinium chloride (CPC) were determined in the presence of salicylate and benzoate ions in the less explored concentration region where viscosity is Newtonian. The cmc of CPC decreased from 9 × 10 −4 to 7 × 10 −7 and 3 × 10 −6 mol kg −1 by adding about 0.3 mol kg −1 of salicylate and benzoate, respectively. The ortho hydroxyl group in salicylate thus has a remarkable influence on the micellization of CPC and the extent of this favorable effect is found to be about 3.5 kJ mol −1. The Corrin–Harkins equation was modified to explain the variation of cmc with electrolyte concentration in the presence of mixed counterions. The slope of the equation does not provide the value of the total counterion binding constant ( β), but gives us information about the lower limit to the value of β, which is found to be 0.66. Addition of salicylate and benzoate increases the counterion binding to CPC micelles compared to that in the presence of chloride alone. An adsorption isotherm was derived to estimate the surface excess of CPC in the presence of mixed counterions.

Preparation, Mechanism, and Supramolecular Structure Study of a Novel Benzimidazole-Hydrate

A novel bis[2-(2-chloro-4-fluorophenyl)-1H-Benzimidazole]-hydrate was prepared from Schiff base, and its single crystalline was obtained. The single crystalline was characterized by X-ray crystallography, and the results shows that the title complex belongs to the triclinic system, space group (P1) with lattice parameters a = 7.592(2) A, b = 7.595(2) A, c = 11.886 (3) A, V = 574(3) A3, Mr = 352.33, Dc = 1.478 g/cm3, μ(MoKα) = 0.33 mm−1, F(000) = 262, Z = 1, the final R = 0.090 and wR = 0.209 for 2,315 observed reflections (I > 2σ(I)). The crystal structure is formed by two benzimidazole molecules which are linked by a water molecule. A UV–Vis spectrophotometer and a fluorophotometer were used to detect the benzimizadole-hydrate crystal transformation process, which shows that benzimidazole-hydrate can only be formed from Schiff base effectively when ortho-hydroxyl group does not exist in benzaldehyde. The synthesis mechanism was also discussed. Compared with its Schiff base, benzimidazole-hydrate displays stronger fluorescence. A novel bis[2-(2-chloro-4-fluorophenyl)-1H-Benzimidazole]-hydrate was prepared, and its single crystalline was obtained and characterized. Its synthesis mechanism was also discussed briefly.

Flavonoid Methylation of Poplar O-Methyltransferase Encoded in Escherichia coli

O-Methyltransferases, which are involved in methylation of secondary metabolites, mediate the methylation of small molecules such as flavonoids, alkaloids, and plant hormones. Among them, flavonoids are an important class of secondary metabolites in plant and exhibit a wide spectrum of pharmacological properties. Modification of flavonoids extend and change pharmaceutical characterization of them as well as the structure. Populus deltoids caffeoyl CoA OMT gene (PopCCoAOMT) was amplified by RT-PCR, cloned and characterized. PopCCoAOMT had a homology of 94% and 90.8% with caffeoyl CoA OMTs of Nicotiana tabacum and Arabidopsis thaliana, and encoded 28.0 kDa in molecular weight. The reaction product of PopCCoAOMT enzyme methylated caffeoyl-CoA, quercetin, and luteolin to feruoyl-CoA, isorhamnetin, and chrisoeryol, respectively. PopCCoAOMT enzyme was shown to be active with compounds associated with substrates having an ortho hydroxyl group and a double bond at between 2 and 3 position of carbon.

4-{[(3-Chlorophenyl)imino]methyl}-3-hydroxyphenyl Myristate

A new Schiff base ester, 4-{[(3-chlorophenyl)imino]methyl}-3-hydroxyphenyl myristate, was synthesized and its IR, 1H NMR, 13C NMR and MS spectroscopic data are presented.

The analytical characterization of a depside in a living species: Spectroscopic and theoretical analysis of lecanoric acid extracted from Parmotrema tinctorum Del. Ex Nyl. lichen

FT-Raman spectroscopy has been used for the analytical characterization of the Parmotrema tinctorum Del. Ex Nyl. lichen. Lecanoric acid, the major lichen chemical present in the total mass, has been extracted from the lichen, purified and characterized by Raman spectroscopy supported by means of theoretical DFT calculations. The calculations indicate that the aromatic ring A of the lecanoric acid structure is kept in the molecular plane by a strong hydrogen bond between the ortho-hydroxyl group of ring A and the ester group; this hydrogen bond is shorter in the C1 isomer form, which is the main feature responsible for the Gibbs free energy difference (−2.96 kcal/mol) favouring the C1 isomer. In spite of the similarity of possible conformers and although many of the predicted Raman bands are found to be common for both forms, there is one Raman transition very characteristic of structure C2, centred at 1815 cm −1, assigned to the stretching of the C O group of the ester moiety ( ν(C O,ester)). For the isomer C1 this transition was predicted at 1729 cm −1, with a lower frequency ascribed to the stronger hydrogen bond present in the latter conformation. In the experimental spectrum two strong bands are found at 1654 and 1638 cm −1 (shoulder) attributed to the C O stretching mode. The analysis of the normal modes for the corresponding transitions calculated at 1742 and 1729 cm −1 allowed the assignment to be made to ν(C O) from the carboxylic acid and ester moiety, respectively. Most of the other Raman bands were also assigned by comparison with the theoretical model. The Raman spectrum obtained directly from the P. tinctorum lichen shows a remarkable similarity with the isolated lecanoric acid spectrum, as well as the presence of bands at 1529 and 1156 cm −1 which are characteristic of a carotenoid species. The results confirm the potential of Raman spectroscopy for taxonomic characterization of lichen species.

Polyphenols based on isoflavones as inhibitors of Helicobacter pylori urease

Twenty polyphenols were synthesized and evaluated for their effect on Helicobacter pylori urease. Among these compounds, 4-( p-hydroxyphenethyl)pyrogallol ( 15) (IC 50 = 0.03 mM) and 7,8,4′-trihydroxyisoflavone ( 19) (IC 50 = 0.14 mM) showed potent inhibitory activities, and inhibited Helicobacter pylori urease in a time-dependent manner. The structure–activity relationship of these polyphenols revealed: the two ortho hydroxyl groups were essential for inhibitory activity of polyphenol. When the C-ring of isoflavone was broken, the inhibitory activity markedly decreased. As for deoxybenzoin, the carboxyl group was clearly detrimental.

Methyl 2,2′,7′-trihydroxy-1,1′-binaphthalene-3-carboxylate acetone solvate

In the title compound, C22H16O5, the two naphthyl units are approximately perpendicular. The 3-naphthyl­carboxyl group and the ortho-hydroxyl group are involved in an inter­molecular O—H⋯O hydrogen bond with O⋯O = 2.606 (2) A. Mol­ecules related by a glide plane are linked by an intermolecular O—H⋯O hydrogen bond with O⋯O = 2.747 (2) A, creating a spiral. A solvent mol­ecule is an acceptor in an O—H⋯O hydrogen bond with O⋯O = 2.700 (2) A.

Phenolic Reactions during Winemaking and Aging

The reactivity of polyphenols is due to the position of the hydroxyl groups on their aromatic nuclei. Ortho-hydroxyl groups promote oxidation while meta-hydroxyl groups induce electrophilic aromatic substitution. Both hydroxylation patterns are encountered in flavonoid structures, on the B and A rings, respectively. In addition to oxidation and electrophilic aromatic substitution, flavonoids undergo nucleophilic addition on the central C ring when it is positively charged. Reactions of the A and C rings are pH-dependent. The A ring of flavonoids undergoes a polycondensation reaction mediated by an aldehyde. The products are anthocyanin and flavanol polymers and copolymers constituted of both. Flavanol polymers are not stable and rearrange into vinyl flavanols and xanthylium pigments. Vinyl flavanols can react with the positively charged C ring of anthocyanins, yielding pyranoanthocyanins, which can also be formed from components that have a reactive double bond, such as carbonyl and ethylene bonds. The positively charged C ring primarily undergoes direct reactions. Since the positive charge on the C ring of anthocyanins and flavanols is pH-dependent, their dehydration and interflavan bond cleavage reactions are also pH-dependent. This leads to flavanol–anthocyanin (F-A⁺) adducts at lower pH values and anthocyanin–flavanol (A⁺-F) adducts above pH 3.8. Temperature seems to favor formation of the latter.

Characterization of an O-methyltransferase from soybean

O-methyltransferases (OMTs) catalyze the transfer of a methyl group from S-adenosine- l-methionine to a hydroxyl group of an acceptor molecule to form methyl ether derivatives and can modify the basic backbone of a secondary metabolite. A new O-methyltransferase, SOMT-9, was cloned from Glycine max and found to encode a protein whose molecular weight is 27-kDa. SOMT-9 was expressed as a GST-fusion protein in Escherichia coli and several compounds such as caffeic acid, esculetin, narigenin, kaempferol, quercetin, and luteolin were tested as putative substrates of SOMT-9. HPLC and NMR results showed that SOMT-9 transfers a methyl group to the 3′-OH group of substrates having ortho-hydroxyl groups. SOMT-9 showed the highest affinity for quercetin, suggesting that SOMT-9 uses a flavonoid as a substrate. Based on its molecular weight and substrate specificity, SOMT-9 belongs to a new class of OMT and is likely to be involved in the biosynthesis of isorhamnetin.

Sorption of naphthoic acids and quinoline compounds to estuarine sediment

The sorption of 16 ionizable organic compounds (IOCs) to an estuarine sediment was measured in synthetic estuarine water as a function of IOC concentration (1–100 μM) at fixed ionic strength (0.4 M), pH (7.6), and sediment concentration (0.018 g sediment kg − 1 suspension). Of the 16 IOCs, 11 were naphthoic acids and five were quinoline compounds. The linear sorption distribution coefficient ( K d) was used to correlate sorption to IOC physicochemical and molecular characteristics. With respect to naphthoic acid, sorption increased with the addition of ortho-substituent groups and with increasing chain length of the 1-acid group, and the greatest increase occurred with ortho-hydroxyl, carbonyl, and carboxyl groups. With respect to quinoline, sorption decreased with substituent group addition (except for nitro group) and with additional heterocyclic N atoms. For the naphthoic acids, log K d exhibited a positive correlation with water solubility (log S w) indicative of sorption primarily to mineral surfaces under the solution chemistry. For the quinoline compounds, log K d exhibited a negative correlation with log S w and a positive correlation with n-octanol/water partition coefficient (log K OW) indicative of sorption primarily to organic matter. For both compounds, poor or no correlations were established between log K d and acid dissociation constant (p K a1), and between log K d and a variety of molecular connectivity indexes. The results from this study demonstrate that the sorption of IOCs differ depending on their backbone structure and may differ between parent compound and ionizable degradation product.

Antioxidant, prooxidant and cytotoxic activity of hydroxylated resveratrol analogues: structure–activity relationship

Resveratrol ( trans-3,4′,5-trihydroxystilbene), a naturally occurring hydroxystilbene, is considered an essential antioxidative constituent of red wine possessing chemopreventive properties. However, resveratrol and even more its metabolite piceatannol were reported to have also cytostatic activities. In order to find out whether this is related to antioxidative properties of those compounds, we synthesized five other polyhydroxylated resveratrol analogues and studied structure–activity relationships between pro-/antioxidant properties and cytotoxicity. Radical scavenging experiments with O 2 − (5,5-dimethyl-1-pyrroline- N-oxide/electron spin resonance (DMPO/ESR)) and 2,2-diphenyl-1-picrylhydrazyl (DPPH ) (photometry) revealed that 3,3′,4′,5-tetrahydroxystilbene (IC 50: 2.69 μM; k 9: 443000 M −1 s −1), 3,4,4′,5-tetrahydroxystilbene (IC 50: 41.5 μM; k 9: 882000 M −1 s −1) and 3,3′,4,4′,5,5′-hexahydroxystilbene (IC 50: 5.02 μM), exerted a more than 6600-fold higher antiradical activity than resveratrol and its two other analogues. Furthermore, in HL-60 leukemic cells hydroxystilbenes with ortho-hydroxyl groups exhibited a more than three-fold higher cytostatic activity compared to hydroxystilbenes with other substitution patterns. Oxidation of ortho-hydroxystilbenes in a microsomal model system resulted in the existence of ortho-semiquinones, which were observed by ESR spectroscopy. Further experiments revealed that these intermediates undergo redox-cycling thereby consuming additional oxygen and forming cytotoxic oxygen radicals. In contrast to compounds with other substitution patterns hydroxystilbenes with one or two resorcinol groups (compounds 1 and 3) did not show an additional oxygen consumption or semiquinone formation. These findings suggest that the increased cytotoxicity of ortho-hydroxystilbenes is related to the presence of ortho-semiquinones formed during metabolism or autoxidation.

Collagen fiber immobilized Myrica rubra tannin and its adsorption to UO2(2+).

Tannins, which are rich in ortho-hydroxyl groups, have a high affinity for UO2(2+). In this paper, Myrica rubra tannin was immobilized on collagen fiber by an aldehydic cross-linking reaction to prepare a novel adsorbent for uranium (UO2(2+)) recovery from wastewater. The adsorption equilibrium, the adsorption kinetics, and the effects of temperature and pH on the adsorption equilibrium were investigated in detail. It was found that the Myrica rubra tannin immobilized on collagen fiber exhibits an excellent adsorption capacity for UO2(2+). The adsorption capacity at 293 K and pH 5.0 was as high as 1.19 mmol UO2(2+)/g (283.3 mgU/g) when the initial concentration of UO2(2+) in solution was 7.5 mmol/L. The adsorption isotherms could be described by the Freundlich equation, and the increase of temperature promoted the adsorption to UO2(2+) . The adsorption kinetics data were fitted very well by the pseudosecond-order rate model, and the equilibrium adsorption capacity calculated by the pseudo-second-order rate model was almost the same as that determined by the actual measurement with the error < or = 4%. The pH has a significant effect on the adsorption process. According to our experiments, the suitable pH scope should be 5-8.

Epigenetic toxicity of hydroxylated biphenyls and hydroxylated polychlorinated biphenyls on normal rat liver epithelial cells.

2-Biphenylol, 3-biphenylol, 2,2'-biphenyldiol, 3,3'-biphenyldiol, 3-chloro-2-biphenylol, and 4,4'-dichloro-3-biphenylol were evaluated using the scrape-loading/dye transfer (SL/ DT) technique to determine in vitro gap junctional intercellular communication (GJIC) in a normal rat liver epithelial cell line as a measure of the epigenetic toxicity. Cytotoxicity was determined using the neutral red uptake assay. A dose range of 0-300 microM was examined. Only 3,3'-biphenyldiol and 4,4'-dichloro-3-biphenylol induced cytotoxicity within the tested dose ranges. Noncytotoxic doses were selected for evaluation of epigenetic toxicity. 4,4'-Dichloro-3-biphenylol was most inhibitory to GJIC at the lowest dose. The cytotoxicity and GJIC inhibitory effects observed for 4,4'-dichloro-3-biphenylol might be, although not exclusively, a consequence of the lipophilic nature of this chemical. 3-Chloro-2-biphenylol was least inhibitory to GJIC. 3-Chloro-2-biphenylol was less inhibitory to GJIC than 2-biphenylol because of the presence of the chlorine functional group, which appears to attenuate the toxic effect of the ortho-hydroxyl group. Although cells were capable of complete recovery of GJIC after removal of each of the chemicals, only with 2,2'-biphenyldiol and 4,4,'-dichloro-3-biphenylol did the cells demonstrate partial recovery without removal of the chemical. The more noncoplanar conformation of 2,2'-biphenyldiol and 2-biphenylol might explain their more inhibitory behavior in comparison to 3,3'-biphenyldiol and 3-biphenylol, respectively.

The role of iron and the factors affecting off-color development of polyphenols.

Iron deficiency affects over two billion people worldwide (Lotfi, M.; Venkatesh Mannar, M. G.; Merx, R. J.; Naber-van den Heuvel, P. Micronutrient Fortification of Foods: Current Practices, Research,and Opportunities; Micronutrient Initiative: Ottawa, Ontario, Canada, 1996). However, fortifying foods with highly bioavailable iron is technically challenging because of off-color and off-flavor development, catalytic degradation of vitamins, and oxidation of lipids. The role of highly bioavailable iron in the off-color development of foods and beverages is not well-understood. The goal of this research was to examine the interaction of iron with simple phenolics and polyphenols. Factors that may affect off-color development, such as pH, oxygen, temperature, and reducing and chelating agents, were evaluated as a model for food products. Our results demonstrated that the iron that reacts with the simple phenolic, catechol, to develop off-color must be in the oxidized state, and the iron is reduced in the presence of catechol. Because this is an oxidation/reduction reaction, the redox potential of all of the components is critical to the color development. Ferrous iron sources with low redox potentials and ferric iron sources with high redox potentials caused off-color development with catechol. Only polyphenols that contain ortho-hydroxyl groups cause off-color development with iron. All of the factors tested affect off-color development and redox potential of the system. Low pH, low oxygen, high temperature, and the presence of reducing and chelating agents inhibited off-color development. To confirm the model, foods that contained these polyphenols were evaluated for off-color development when iron was added. The foods tested reacted similarly to the models of polyphenols with iron. Off-color development was caused by oxidation-reduction interactions between ferric iron and polyphenols that contained ortho-dihydroxyl groups. Ferrous iron needed to be oxidized to participate in off-color development. In addition, methods identified in the models to prevent off-color development were effective in most of the food products examined. Using the ferrous form of iron and maintaining it in its reduced form by lowering pH, removing oxygen, and including reducing agents, it was possible to fortify foods with highly bioavailable iron.

Substituent effects on O--H bond dissociation enthalpies and ionization potentials of catechols: a DFT study and its implications in the rational design of phenolic antioxidants and elucidation of structure-activity relationships for flavonoid antioxidants.

Density functional theory (DFT) on B3LYP/6-31G(d,p) level was employed to investigate the substituent effects on O--H bond dissociation enthalpies (BDEs) and ionization potentials (IPs) of catechols. It was revealed that the ortho hydroxyl of catechol was effective for the reduction of the O--H BDE; however, the group had little influence on the IP. The para substituent effects upon O--H BDEs and IPs for catechols were roughly the same as those for monophenols, and this gave the catechol moiety more potential than monophenol to be used as a lead compound in rational design of phenolic antioxidants. In addition, the 1,4-pyrone effects on O--H BDEs of catecholic rings A or B of flavonoids were also investigated. Although 1,4-pyrone extended the conjugation system of flavonoids, it was not beneficial to reduce the O--H BDE as a result of its electron-withdrawing property. Thus, 1,4-pyrone was unlikely to be favorable to enhance the H-abstraction activity of flavonoids.

Z' = 4 structure without obvious pseudosymmetry: implications for the formation of solid-state compounds.

Crystals of 4-chloro-2'-biphenylol grown at 263 K and studied at both 293 and 142 K are loosely packed and contain OH.O bonded tetramers composed of four crystallographically independent molecules (Z' = 4). Approximate symmetry relationships between independent molecules are apparent in many, perhaps even most, structures with Z' > 1, but are not obvious in this structure. The inefficient crystal packing, the surprisingly large value of Z' and the absence of pseudosymmetry reflect the difficulty of finding a dense molecular arrangement that also allows for hydrogen-bond formation. Impediments to good packing are the steric congestion around the ortho hydroxyl groups and the difficulty in filling space with significantly twisted biphenyl fragments. The packing arrangement adopted is strongly reminiscent of the structure type found for eight simple 4,4'-biphenyl derivatives, but one of the four independent 4-chloro-2'-biphenylol molecules has an orientation that is significantly different from the orientations of the other three and that does not fit the 4,4'-XPhPhY pattern. It is suggested that molecules that crystallize with Z' > 1 are good candidates for solid-state compound formation.