vanadium(v) oxyanions. the dependence of vanadate alkyl ester formation on the p k ...

Vanadium(V) oxyanions. The dependence of vanadate alkyl ester formation on the pkl, of the parent alcohols

ALAN S. TRACEY, BRUNO GALEFFI, AND SOROUSH MAHJOUR Department of Chemistry, Simon Fraser University, Burnab)), B.C., Canado V5A IS6

Received January 22, 1988

ALAN S. TRACEY, BRUNO GALEFFI and SOROUSH MAHJOUR. Can. J. Chem. 66, 2294 (1988) The interaction of vanadate (V04H11-) with a variety of alkyl alcohol's (ROH) covering about seven pK, units of acidity

have been studied in aqueous solution by ''v nuclear magnetic resonance spectroscopy. A linear free energy relationship between the equilibrium constant for the formation of the vanadate monoester ( H O V O ~ R ' ~ ) and the acidity of the alcohol was established at 23'C. The correlation was found to be log I/K = -(0.09 ? 0 . 0 2 ) ~ ~ : ~ ~ + 2.1 k 0.3 where K = [HOV03R1-I/ [V04H11-] [ROH]. This correlation was shown not to extend to ligands with T-bonding capability such as phenols or phosphates, where the products are highly favoured relative to the alkyl esters. An interesting correlation between pK, values of the product esters and the pK, of the parent alcohols was also observed. It was found that below a p~:OH of about 15 the pK, values of the esters were essentially constant. However, above this value of 15 the pK, of the ester was found to increase rapidly with an increase in pK, of the alcohol. This result may indicate that the electron accepting ability of the metal is exhausted with the higher pK, alcohols, and the extra electron density is transferred to the oxygens, thus causing an increase in pK, of the ester.

ALAN S. TRACEY, BRUNO GALEFFI et SOROUSH MAHJOUR. Can. J. Chem. 66, 2294 (1988). Operant en solution aqueuse et utilisant la spectroscopic rmn du 5 1 ~ , on a CtudiC I'interaction du vanadate (VO4HZ1-) avec

un grand nombre d'alcools aliphatiques (ROH) couvrant sept unitts de pK,. A 23"C, on a pu etablir une relation lintaire d'Cnergie libre entre la constante d'kquilibre pour la formation du monoester de vanadate (HOVO~RI-) et l'aciditk des alcools. On a trouvt que la corrilation prend la forme de log 1/K = -(0,09 k 0 , 0 2 ) ~ ~ : ' ~ + 2 , l k 0,3, dans laquelle K = [ H O V O ~ R ' - ] / [ V O ~ H ~ ~ - ] [ROH]. On a dCmontrC que cette corrClation ne s'ttend pas aux ligands prCsentant une capacitt de liaison par des Clectrons T, comme les phCnols ou les phosphates; dans ces cas, les produits sont trks favorisCs par rapport aux esters d'alkyles. On a aussi observC une corrtlation inttressante entre les valeurs des pK, des esters qui se foment comme produits et les pK, des alcools qui leur donnent naissance. On a trouvt qu'en-dessous d'une valeur de 15 pour le p~:OH, les ialeurs des p ~ , des esters augmentent rapidement avec une augmentation du pK, des alcools. Ce rtsultat semble indiquer que la facilitt du mCtal i accepter des Clectrons est CpuisCe avec les alcools de pK, ClevC et que la densitt Clectronique additionnelle est transferee aux oxygknes; ceci provoque une augmentation du pK, de I'ester.

[Traduit par la revue]

Introduction The aqueous chemistry of the higher oxidation states of

vanadium is attracting increasing attention in chemistry and biochemistry. There is considerable evidence that vanadium is an essential element for animals (1, 2). Vanadium is found in the enzyme systems of some nitrogen-fixing bacteria (3, 4) and is apparently utilized in the halogenation processes of a variety of seaweeds (4). Vanadium(V) (vanadate) and vanadium(1V) (vanadyl) oxyanions can have a large effect on the function of a variety of enzymes either as an activator or inhibitor of the enzyme function (1, 5). The ability of vanadate to affect enzyme function seems to arise, at least in part, from the ability of vanadate to act as a phosphate analogue.

The condensation of phosphate with hydroxylic compounds to form a phosphate derivative is, to a significant extent, depen- dent on the acidity of the hydroxyl group. Thus, the formation constant for phosphate esters of alkyl alcohols is comparatively favourable, comparable in fact to the formation constant for alkyl vanadates as for instance in the case of formation of phosphate and vanadate esters of ethanol (6). The formation of phosphate esters of phenols is, by comparison, highly unfav- ourable when compared with those for ethyl phosphate and phenyl vanadate (7). An investigation of this phenomenon has shown that there is a direct relationship between the acidity constant, K,, of the parent hydroxylic compound and the formation or hydrolysis constant for the phosphate ester (8).

The equilibrium constant for hydrolysis of the phosphate ester dianion is related to the pKa of the parent hydroxyl group

by eq. [ l l ,

[:I] log K = - 1 . 3 5 p ~ F 0 H + 7.50

where K is the hydrolysis constant defined by eq. [2] and p ~ F O H is the pKa of the hydroxyl group of interest (8). In eq. [21

[21 HOPO,~- + H + + RO- e ROPO,Z- K

K = HOP^^'-] [H'] [RO-] / [ROPO~~-]

the formation of water is not explicitly considered. In view of the linear free energy relationship between product formation and the pK, of the hydroxyl group expressed by eq. [ I ] for phosphate, it was decided to investigate the vanadate system in more detail, particularly in view of the fact that the available information suggested that the vanadate system showed much more complex behaviour.

5'V nuclear magnetic resonance (NMR) spectroscopy allows direct measurement of the equilibria since separate signals from the vanadium products and precursors, in general, are observed in the NMR spectra. Simple correlations, determined as a function of ligand or vanadate concentration, or of pH provide the requisite information.

Experimental Materials

Reagent grade chemicals were used without further purification. Proton NMR spectra indicated that all the alkyl alcohols used in this

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TRACE Y ET AL. 2295

study were greater than 97% pure. Preparation of stock solutions and final solutions followed procedures previously described (6, 9).

Spectroscopy All 5 1 ~ NMR spectra were obtained at ambient temperature from a

Bruker WM-400 NMR spectrometer operating at the vanadium fre- quency of 105.2MHz. Spectral widths of 40kHz, 50" pulse widths and 0.05 s acquisition times were used for all spectra. Relative signal intensities were obtained using the integration routine supplied by the instrument manufacturer. No effort to obtain more accurate integrals through use of line-fitting or other methods was made. Chemical shifts are reported relative to that of VOC13 at 0.0ppm.

Methods The methods employed for determination of equilibrium constants

for formation of the vanadate esters have been described in detail elsewhere as have the procedures employed for the determination of the pKa values for those compounds with ionizable protons (6). No significant changes have been made to those methods in this study.

Results and discussion The vanadate ion spontaneously and reversibly condenses

with a variety of molecules containing hydroxyl groups to provide esterified vanadate derivatives (6, 7, 9, 10). This condensation has been shown to be reasonably favourable both for the ions v04H2- and VO4HZp with the individual condensations apparently occumng in the manner indicated in Scheme 1 where 1 refers to the ligand.

In Scheme 1 the esterification reactions tend to be slow on the NMR time scale and as a consequence separate NMR signals can generally be observed for vanadate and its mono- and diesters. Proton exchange, on the other hand, is fast and be- cause of the rapid proton exchange it is not possible to measure Ki and K; independently of each other in an NMR experiment but, rather, only an observed equilibrium, K1, which is depen- dent on Ka2 and Kg2, can be measured, K1 is defined by eq. [3], and water formation is not explicitly considered. In eq. [3], Ti refers to tetrahedral vanadate, VO4H2- plus v O ~ H ~ - , and T1 to the product esters.

Expressing K1 in terms of K;, Ka2 and KL2 of Scheme 1 yields eq. 141.

It is evident that if K1 is determined for a variety of pH values near Ka2 and Ki2, then all the constants of eq. [4] can be determined and as well K; of Scheme 1. In practice, it is easier to measure Ka2 and Kg2 directly since these values can be determined by the effect of pH on the chemical shifts of the 5'V NMR signals corresponding to Ti and T1. A change in protonation state of vanadate or its monoester has a substantial effect on the shielding of the vanadium nucleus. At a pH well below the pKa2 of vanadate, the vanadate species in solution is VO4HZ1-, which is characterized by a chemical shift 6, at a pH well above pKa2, the species in solution is ~ 0 4 ~ ~ - with the chemical shift Sh. At intermediate pH values the observed shift, 6, is related to the pH and pKa by eq. [5],

6 - 61 [5] pH = pKa + log -

Sh - 6

It is useful to note that when the logarithmic term is plotted against pH the slope of the straight line should be 1. This provides a convenient test of the applicability of eq. [5] to the system being studied. Equation [5] is also applicable to the vanadate monoester but not the diester V0412'-, since the diester has no proton to lose. In this case the 5 1 ~ chemical shift should be pH-independent. This has been demonstrated for the vanadatelethanol system (6) and has been observed here. Table 1 gives the chemical shifts and pKa values for vanadate and its esters for a variety of alcohol solutions.

Knowledge of the Ka2 and Kg2 values for vanadate and its esters then provides Ki simply by determining K1 of eq. [2] at any pH and applying eq. [4]. Of course K1 must be determined within a pH range much lower than the pKa for the alcohol or pKa3 of vanadate and well above pKal for vanadate or its ester. If this is not done, Scheme 1 must be expanded appropriately. Fortunately the pKal values are low, about 3.0 for vanadate (1 1, 12), while pKa3 of vanadate and the pKa of the alcohols except for hexafluoroisopropanol are quite high (pKa for CF3- CHOHCF3 = 9.3, pKa ( v O ~ H ~ - ) - 13 (12)). From the various equilibrium constants measured at a pH near 7 and the known Ka values the respective Ki and K; were calculated and collected into Table 2.

From the entires of Table 2 it can be seen that the Ka values for the alcohols of this study range over about 7 orders of magnitude from pKa = 9.3 for (CF3)2CHOH to -16.8 for t-butanol. Despite this large change in pKa values, the formation constants of the various esters ranges only from about 0.20 M-' for the higher pKa values to 0.06 M-' for the lower values. The decrease in formation constants, although small, follows the decrease in pKa of the alcohols. This result does show that ester formation is not particularly sensitive to the pKa of the alcohol. It can, however, be shown that, with the exception of the methyl and t-butyl vanadate esters, there is a linear free energy relationship between the pKa of the alcohol and the hydrolysis (or formation) constant of the ester as can be seen by plotting log (1 /Ki) versus the pKa of the parent alcohol. When this was done a straight line of slope -0.09 k 0.02 and intercept $2.1 a 0.3 as shown in Fig. 1 was obtained. The very small slope of this correlation illustrates the insensitivity of ester formation to the electron withdrawing ability of the ligand, RO-.

This line has a slope of - 1.09 a 0.02 when cast into the form of eq. [I], for which a slope of - 1.0 indicates that ester formation is independent of the pKa of the parent alcohol. It is

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2296 CAN. J . CHEM. VOL. 66, 1988

TABLE 1 . Vanadate and vanadate ester pKa values and 5 1 ~ chemical shifts determined for various aqueous alcohol solution^".^

V04H2'- ROV03H1- (R0)2V02'- [ROH]

Alcohol 61 8h pKa2 61 8h PK:~ pK;2 6 M Reference

Methanol Ethanol Isopropanol 2-Butanol r-Butanol 2-Cyanoethanol 2,2,2-Trifluoroethanol Propargyl alcohol 1,1,1,3,3,3-Hexafluoro-

2-propanol Ethylene glycol

15 6

10 This work

10 This work This work This work

This work 16

'pK, values were determined by varying the pH under conditions of 2 0 m M HEPES buffer and the indicated concentrations of alcohol. bAbbreviations are: S,, limiting 5'V chemical shift at low pH; S,, limiting shift at high pH; 6, 5'V chemical shift for the vanadate diester; ROH, the alcohol

being considered.

TABLE 2. Formation constants for vanadate ester anions derived from a variety of alcohols

Alcohol pKa Ki(M-I) K;'(M-') K?(M-') Alcohol pKa Ki (M-') K;' (M-') K2 (M-I)

"Equilibrium constants are those defined by Scheme 1 and were determined as discussed in the text. Estimated errors for all equilibrium constants are about 10% of the reported values except for the K2 values where the errors are about ?O.Ol M - ' for all measurements.

bAlcohol pK, values were taken from tabulations in ref. 17. 'The pK, for this alcohol was estimated from values for related compounds tabulated in ref. 17. dThe statistical factor of two is removed from reported formation constants (ref. 16) to give the formation constants K,' and K;'.

S lope =0.09 '002

Intercept = 2.1 z0.3

FIG. 1. The linear free energy relationship between the vanadate ester hydrolysis constants and the acidity constants of the product alcohols is shown. The experimental points are taken from the data of Table 2.

evident then, that phosphate alkyl ester formation is consider- comparable to that attributable to electron withdrawal or dona- ably more sensitive than vanadate alkyl ester formation to the tion as is evident for the formation of t-butyl vanadate, Ki = pK, of the alcohol. In fact the formation of vanadate alkyl 0.095 k 0.005M-' (lo), 1-vanado-3-hydroxybutane, K; = esters shows a sensitivity to neighbouring substituents which is 0.25 k 0.01 M-' (lo), 1-hydroxy-3-vanadobutane, Ki = 0.29

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TRACEY ET AL.

FIG. 2. The free energy relationship between the acidity constant of the vanadate esters, HOV03R, and those of the parent alcohols, ROH. The experimental points are taken from Table 1. (Note that the pKi2 of this figure corresponds to the pK& of Table I .)

2 0.02 M-' (10) and2-vanadopropionate, K; = 0.54 2 0.05 M-' (13).

Interestingly enough, when an attempt was made to expand the considerations of pK, to include hydroxylic compounds other than the alkyl alcohol systems of Table 2 , no simple relationship between the pK, of the parent hydroxyl and product formation was found. For instance, phosphate (P04H2-) with a pK, of 6.70 readily forms a phosphovanadate anhydride, from VO4H2-, with a formation constant of 64 * 3 M- ' (9). This value is much larger than the formation constants for vanadate esters from alkyl alcohols (Table 2) and clearly shows the presence of strong product stabilizing interactions which oppose the destabilizing interactions of electron withdrawal. Such stabilizing interactions apparently are much less significant for the case of formation of pyrophosphate from phosphate since pyrophosphate is a high energy phosphate product.

Somewhat similar behaviour is observed in the case of phenol. Phenylvanadate is formed with a formation constant of 1 .OM- (7), a value about 15 times larger than that expected for alkyl vanadates formed from alkyl alcohols of a similar p~:'~, but about 4 orders of magnitude larger than phenyl phosphate formation (7). Behaviour such as this may indicate that the en- hanced stabilization arises from vanadium d-orbital interactions with the T-system of the ligand. A variety of substituted phenols is currently being studied in an attempt to obtain more information concerning the factors influencing vanadate condensation reactions.

An additional point to be made from the information of Table 2 is that as the pK, of the parent alcohol increases, the formation (K;) of ~ 0 ~ 0 3 ~ - from V 0 4 ~ ' - becomes increas- ingly favoured relative to the formation (Ki) of ROV03H- from VO4HZp. For example, for the very high pKa alcohols such as t-butanol and s-butanol the proportion K;: K;' is about 20: 1 whereas with the low pK, alcohols this proportion is about 1 : 1.

The effect that the aqueous solutions of the different alcohols have on the pKa2 of vanadate is rather small but significant. In general, the alcohol tends to increase the pK, thus favouring the least ionized form of vanadate. Similar considerations also apply to the vanadate ester. If the effects of alcohol on the pK, of VO4HZ1- and on the pK, of the ester ROV03H1- are similar, then the pKa of the ester in dilute solution can be estimated by applying a correction factor obtained by compar-

ing the pK, of V 0 4 ~ 2 1 - in water (pKa2 = 8.2) to that observed for the aqueous alcoholic solutions in which the pK, was measured (Table l). The ester pK, values estimated by this procedure are tabulated in Table 1 under pKi2. corrections obtained by this type of procedure have been shown to be valid from studies of the effect of solvent on acidlbase equilibria where it was concluded that solvent does not affect the relative strengths of acids as long as they are the same charge and same chemical type (14).

An interesting point of this study is revealed when the pKEz values of the alkyl esters and their parent alcohols are compared as shown in Fig. 2. From this graph it is seen that for alcohols with a pK, below about 15, the pK;, values of the product esters are essentially constant; however, at a p ~ E O H of about 15, the pKgz of the esters rise rapidly with increase in pK, of the parent alcohols. The reason for this is not clear, but the behaviour indicates that the vanadium centre becomes satu- rated with electrons and any further electrons inductively intro- duced to the coordination centre are redistributed to the oxygens of the vanadate thus increasing pK&. Below the critical p ~ E O H the electron density may be localized to the vanadium centre. This behaviour is reminiscent of that observed for a homologous series of bidentate ligands where it was found that the coordination geometry and protonation state of the product vanadium(V) derivative depended in a rather subtle manner on the oxidation state of the ligand (13).

Acknowledgement Thanks are gratefully extended to the Natural Sciences and

Engineering Research Council of Canada for its support of this work.

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vanadium(v) oxyanions. the dependence of vanadate alkyl ester formation on the p k ...

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