1028
J. Phys. Chem. 1003, 87, 1928-1931
fails seriously, possible assumptions are that each collision removes a constant amount of energy, independent of the initial internal energy, or that each collision removes a constant fraction of the initial energy. Rossi and Barkerlo claim to have demonstrated that the second model describes energy transfer from excited azulene to cold azulene, and this model is also used by Houriet and Futrell" in analyzing energy transfer from (C5H9')* to methane. The present experiments cannot distinguish between the two possibilities and provide only the total number of collisions to quench. If we assume constant energy loss per collision, a methane collision would remove about 300 cm-', a cyclohexane collision about 2000 cm-', and an iodobenzene collision about 6000 cm-'. If the ion loses a constant fraction of its energy on each collision, that fraction would be -50% for C6H,I, 20% for cyclohexane, and 3% for methane. Other studies of energy transfer from ions have yielded a variety of results. The results of Kim and D u n b d have already been discussed. For collisions of C5Hg+with CHI in a tandem ICR, the average energy transferred was found to be 1400 cm-l." Rosenfeld et a1.I2 reported that ap(10) Rossi, M. J.; Barker, J. R. Chem. Phys. Lett. 1982,85, 21. (11) Houriet, R.; Futrell, J. H. in 'Advances in Mass Spectroscopy"; Daly, N. R., Ed.; Heyden: London, 1978 Vol. 7A.
proximately 100 collisions are required to cool CH30HFformed with 15 kcal of excess energy, when the colliding gas is methyl formate. Freiser and Beauchamp13found that, in a two-photon ICR experiment like the one described here, CH3CN was approximately 25% as effective in quenching excited benzene ions as benzene itself. A range of collision efficiencies has thus been reported, with no systematic explanation of which factors determine the efficiency. Further studies, with a systematic variation of the properties of the bath gas, are in progress. Acknowledgment. The support of the donors of the Petroleum Research Fund, administered by the American Chemical Society, and of the National Science Foundation, is gratefully acknowledged. N.B.L. acknowledges with gratitude the support of a Goodrich predoctoral fellowship during part of the period of this research. Registry No. C6H51+,38406-85-8; CBH& 591-50-4; CsHI2, 110-82-7;CHI, 74-82-8. (12) Rosenfeld, R. N.; Jasinski, J. M.; Brauman, J. I. J. Am. Chem.
SOC. 1979,101, 3999. (13) Freiser, B. S.; Beauchamp, J. L. Chem. Phys. Lett. 1975,35, 35. (14) We note for completeness the expression analogous to eq 10 for a bath gas different from the parent: 2/32
+-
R2t2
Fluorine-I9 Relaxation Study of Perfluoro Chemicals as Oxygen Carriers PeJmanParhaml and B. M. Fung' Deperrment of Chemistry, University of Oklehoma, Norman, Oklahoma 73019 (Received: November 4, 1982; In Final Form: December 27, 1982)
Fluorine-19 magnetic relaxation of fluorine atoms in cis- and trans-perfluorodecalin,perfluorotributylamine, and an emulsion of perfluorotributylamine in water was studied at 75.38 MHz and 298 K. It was found that the longitudinal relaxation rate (l/Tl) of each fluorine nucleus depended linearly on the partial pressure of oxygen in mixtures of N2 and O2that were used to saturate the liquids. The slopes of the plots were different for each type of fluorine atom in a perfluoro chemical. This was explained by the preferential approach of oxygen to some parts of the organic molecule over other parts. This is likely due to steric effect rather than specific binding.
Introduction A number of perfluorinated organic compounds is widely used as blood substitutes.' They are often called perfluoro chemicals (PFC). The PFC's can be used as blood substitutes because they are good carriers of oxygen and carbon dioxide, inert, nontoxic, and can be transpired from the body. Over the past 16 years, a great deal of progress have been made in the field of PFC blood substitutes.',2 Numerous experiments on animals have been performed,'J and a number of clinical tests has been reported recently.H (1) J. G. Riess and M. LeBlanc, Angew. Chem. Znt. Ed. Engl., 17,621 (1978). (2) R. P. Geyer, K. Taylor, R. Eccles, T. Zerbonne, and C. Keller, "Abstractof Papers",183rd National Meeting of the American Chemical Society, Las Vegas, NV, Mar 28-April 2, 1982; American Chemical Society: Washington, DC; FLUO1. (3) T. H. Maugh, 2nd, Science 206, 205 (1979). (4) E. R. Gonzalez, J. Am. Med. Assoc., 243, 720 (1980). (5) K. K. Tremper, R. Lapin, E. Levine, A. Friedman, W. C. Shoemaker, Crit. Care Med., 8, 738 (1980). (6) K. Honda, S.Hoshino, M. Shoji, A. Usuba, R. Motoki, M. Tsuboi, H. Inoue, and F. Iwaya, N . Engl. J. Med., 303, 391 (1980).
The most commonly used PFC's to date are perfluorodecalin (octadecafluorodecahydronaphthalene), per, fluorotripropylamine (heneicosafluorotri-n-propylamine) and perfluorotributylamine (heptacosafluorotri-n-butylamine). In preparing a blood substitute, one or several PFC's are usually emulsified in a Ringer's solution, using Pluronic F 68 (a block polymer of poly(ethy1ene oxide) and poly(propy1ene oxide)) as a emulsifier. Other PFC's and fluorinated surfactants developed recently can form more stable emulsion^.^ While hemoglobin has a definite binding for molecular oxygen, PFC's probably act as simple solvents for oxygen and other gases.2 The volume of oxygen dissolved in the (7) R. C . Xiong, Chung-hua Wai R o Tsa Chih (Peking),19, 213 (1981); MEDLINE 0530118 81260118 (1982). (8) T. Suyama, K. Yokoyama, and R. Naito, b o g . Clin. Biol. Res., 55, 609 (1981). (9) R. E. Moore and L. C. Clark, Jr., "Abstract of Papers", 183rd National Meeting of the American Chemical Society, Las Vegas, NV, Mar 28-April 2,1982; American Chemical Society: Washington, DC; FLUO5; manuscript submitted for publication.
0022-3654/83/2087-1928$01.50/00 1983 American Chemical Society
F-19 Study of Perfluoro chemicals as O2 Carriers
The Journal of Physlcal Chemistry, Vol. 87, No. 11, 1983 1929
s-I atm-') for Different PFC's
TABLE I : Slopes of F-19 1/T, vs. Po cis-perfluorodecalin trans-perfluorodecalin perfluorotributylamine (neat)
1(4,5,8) 2.24 f 0.06 1(4,5,8)a 2.17 f 0.08 CY
2.16 perfluorotributylamine (emulsion)
f
0.06
01
2.08
f
0.08
1(4,5,8)e 2.15 f 0.04
2(3,6,7) 2.33 f 0.03 2(3,6,7)a 2.20 f 0.03
2(3,6,7 )e 2.45 f 0.05
P
Y
6
1.75 f 0.07
1.79 f 0.14
2.44
P
Y
6
1.78 f 0.11
2.36
1.79 f 0.12
PFC emulsions obeys Henry's law.' Although the PFC's do not show definite interactions with oxygen, we were interested to find out whether the oxygen molecules dissolved have equal access to various parts of a PFC molecule, or if there is a preferred orientation for oxygen to approach the PFC molecule. The technique used in this study was F-19 nuclear magnetic resonance (NMR).
Experimental Section Perfluorodecalin was obtained as a mixture of cis and trans isomers from PCR Research Chemicals, Inc. The two isomers were separated on a 3.3-m GC column with 10% SE-30 on 60-80 chrom-P-N AW. Perfluorotributylamine was obtained from Columbia Organic Chemicals, and Pluronic F 68 was obtained from 3M Co. They were used without further purification. Emulsions of perfluorotributylamine were prepared by sonicating the PFC (10% by volume) and Pluronic F 68 (4% by weight) in water for 10 min, using a bath type sonicator (Model GllBSPlT, Lab Supplies Co., Inc.). A vacuum line was used to mix various amounts of N2 and O2in a 2-dm3flask to reach a total pressure of 1.2 atm. Each sample for the NMR study was prepared by placing the PFC liquid or emulsion in a 5-mm (0.d.) NMR tube and bubbling the solution with the gas mixture for 30 min. The tube was immediately capped but not sealed. Further gas exchange was negligible within a few hours, since repeated measurements yielded the same values of Tl. F-19 relaxation studies were carried out at 75.38 MHz and 298 K with an IBM NR/80 spectrometer. A proton probe was used to observe the F-19 resonance, and a deuterium external lock was used for field-frequency stabilization. The inversion-recovery method was used to measure the F-19 longitudinal relaxation time (TJ. Results In principal, the signal intensity (Mo- M) for a multispin system is a polyexponential function of the pulse interval ( 7 ) in the inversion-recovery method of Tl measurement. However, the deviation from a single exponential is hard to detect for most systems when a nonselective 180° pulse is used. In our measurements, all of our data yielded - M) vs. T , excellent straight lines for the plots of In (Mo with less than 2% standard errors for the slopes. Therefore, apparent values of l/Tl were obtained from linear least-squares analysis of the data. At 298 K, cis-perfluorodecalin is in rapid conformational equalibrium, with both rings interconverting between two chair forms. The axial and equatorial fluorine atoms are indistinguishable, and the F-19 NMR spectrum has three peaks due to the 1(4,5,8),2(3,6,7), and 9(10) fluorines, respectively.'O The spin-spin splittings were not resolved at 75.38 MHz. The longitudinal relaxation rates (l/Tl) of the fluorine nuclei were studied as functions of the partial pressure of oxygen in mixtures of N2 and O2that were used to saturate the liquid, and the results are plotted in Figure 1.
f
0.03
f
0.10
9(10) 2.11 f 0.05 9(10) 1.79 f 0.08
31
0
02
0.4
06
0.8
1.0
Partial pressure of oxygen,otm
Figure 1. F-19 longitudinal relaxation rates for cis-perfluorodecalin at 75.38 MHz and 298 K: A, 1(4,5,8) fluorine; 0,2(3,6,7) fluorine; 0, 9( 10) fluorine.
trans-Perfluorodecalin is a more rigid molecule, because each ring can have only one chair conformation, and the boat forms are not favorable. The axial and equatorial fluorines in the 1(4,5,8)and 2(3,6,7)positions have different chemical shifts, and are strongly coupled to one another. They show two overlapping AB quartets in the F-19 NMR spectrum at 75.38 MHz. An assignment of the spectrum at 30 MHz was made previously," but it is ambiguous and probably incorrect. We have used a new technique of multiplet selection based upon double quantum coherencell to make a new assignment, and the discussions are presented elsewhere.12 Based upon this assignment, the longitudinal relaxation rates of each type of fluorine nucleus could be studied. The results are plotted against the partial pressure of oxygen and shown in Figure 2. Perfluorotributylamine shows four peaks in the F-19 NMR spectrum. Spin-spin splittings were not resolved at 75.38 MHZ. Assignments of the peaks can be easily made from the data of chemical shifts and peak intensities. When the F-19 longitudinal relaxation rates were plotted against the partial pressure of oxygen, they also showed straight lines with different slopes for the four types of fluorine atoms. The results are shown in Table I, which gives the slopes obtained from linear least-squares calculations. Since perfluorotributylamine forms a stable emulsion in water with Pluronic F 68 as an emulsifier, the F-19 longitudinal relaxation rates of the emulsion were also studied. The results are shown in Figure 3.
Discussion The data in Figures 1-3 show that the F-19 longitudinal relaxation rate of each fluorine nucleus in all three compounds depends linearly on the partial pressure of oxygen. The reason for this is the following. There are two types (11)P.J. Hore, E. R. P. Zinderweg, K. Nicolay, K.Dijkstra, and R.
(10)J. Homer and L. F. Thomas, h o c . Chem. Soc., 139 (1961).
Kaptein, J. Am. Chem. SOC., 104, 4286 (1982).
(12)B. M.Fung, Org. Magn. Reson., in press.
1930
The Journal of Physical Chemistry, Vol. 87,No 11. 1983
Parhami and Fung
for each PFC, different slopes of the plots (Figures 1-3) reflect differences in the paramagnetic relaxation rates. The differences imply that oxygen has a preferred approach to each PFC molecule, as it can be explained in the following way. The relaxation rate of a nuclear spin system due to the interaction with a paramagnetic species is13
0
02 04 06 08 IO Partial pressure of oxygen, atm
Figure 2. F-19 longitudinal relaxation rates for trsns-perfluorodecalln at 75.38 MHz and 298 K: 0, 1(4,5,8)a fluorine; A, 1(4,5,8)e fluorine; 0, 2(3,6,7)a fluorine; W, 2(3,6,4)e fluorine; 0, 9(10) fluorine. Only one line is drawn for the l a , le, and 2a fluorines to avoid confusion.
4
t
VI
F \
-
0
0 2 04 06 08 IO Partial pressure o f oxygen, atm
Figure 3, F-19 longitudinal relaxation rate for a 10% emulsion of perfluorotributylamine In water (4 % Pluronic F 68) at 75.38 MHz and 298 K: A, CY fluorine: 0, p fluorine; 0, y fluorine; 0, 6 fluorine.
of PFC molecules. The ones free of oxygen have an apparent longitudinal relaxation rate of 1/ Tld, and the ones with oxygen in their immediate vicinity have an apparent longitudinal relaxation rate of l/Tld + l/Tlp, where l/Tlp is the paramagnetic contribution of oxygen. Since the oxygen molecules rapidly diffuse in the solvent, the observed relaxation rate for each type of fluorine atom is a weighted average:
1 = (1 - x ) 1 + Tl
.( & + &)
= - 1+ -
Tld
Tld
x T1p
(1)
where x is the mole fraction of oxygen. Since the solubility of oxygen in the PFC’s obeys Henry’s law,’ eq 1 becomes
_1 - -1 + -Po, TI
Tld
kT1p
where Po, is the partial pressure of oxygen, and k is Henry’s law constant. Thus, the plot of l/Tl vs. PO,should be linear, with a slope of l / ( k T g ) . Since k is a constant
where S is the total electron spin of the paramagnetic y is the nuclear gyromagnetic ratio, species (S = 1 for 02), g/3 is the electron magnetic moment, r is the distance between the paramagnetic center and the nucleus concerned, usis the angular frequency of electron resonance, oIis the angular frequency of nuclear resonance, and T , is the correlation time for the reorientation of the coupled magnetic moment vectors: -1= - 1+ - +1 - 1 (4) 7c
7,
TI
7e
where T~ is the electron spin relaxation time, T , is the rotational correlation time, and 7, is the residence time of the paramagnetic species. In eq 3, the contribution due to contact interaction is neglected, because oxygen does not form a complex with the PFC’s, and the hyperfine interaction would be very small. Equation 3 indicates that the paramagnetic relaxation rate is inversely proportional to r6. In other words, if the average distances between the oxygen molecule and various fluorine atoms in a PFC are different, the slope of the plot of l/T1 vs. Po would be larger for the fluorine nuclei that are closer to the oxygen molecule. The differences in the slopes would diminish if spin diffusion within the molecule is effective. The slopes of the plots for cis-perfluorodecalin, trans-perfluorodecalin, perfluorotributylamine, and an emulsion of the latter are summarized in Table I. The results show that the average distances between oxygen and various fluorine nuclei in a PFC molecule are not the same. It is difficult to determine whether spin diffusion has actually caused the differences in the slopes to be less than those due to the paramagnetic effect alone. Qualitatively, the preferred directions of approach of O2 to cis-perfluorodecalin are the ends of the molecule (positions 2,3,6, and 7), and the bridgehead positions (9 and 10) are the least favored. This situation is more obvious for trans-perfluorodecalin. A space-filling model shows that its shape is like a prolate ellipsoid. The equatorial fluorines at the 2,3,6, and 7 positions point out at the ends, the equatorial fluorines at the 1 , 4 , 5 , and 8 positions point out at the sides, all axial fluorines are on the two faces, and the 9 and 10 fluorines are near the centers of the faces. The slopes of l / T 1 vs. Po, are such that 2e > l e 2a l a > 9 (Table I). This indicates that oxygen prefers to approach trans-perfluorodecalin from the ends much more than the bridgehead positions. For perfluorotributylamine, the slopes of the plots imply that the most preferable positions for oxygen to approach the molecule are the terminal trifluoromethyl groups ( 6 ) , the next ones are difluoromethylene groups connected to the nitrogen atom ( a ) , and the least favored positions are the difluoromethylene groups in the middle (@,y ) . There are no significant differences between the slopes for individual fluorine atoms in the neat liquid and in the emulsion. This implies that, at the concentration studied, the surfactant
- -
(13) I. Solomon, Phys. Reu., 99, 559 (1955).
J. Phys. Chem. 1983, 87, 1931-1937
did not appreciably affect the interaction between oxygen and the PFC. The preferences of the approach of oxygen to different parts of the PFC's are most likely due to steric factors rather than specific binding. For example, if O2 binds to one end of the trans-perfluorodecalin molecule, we would expect the slope of 1/T, vs. PO,for the 2e fluorine to be about 200 times that of the 9-fluorine because of the l/r6 dependence. The observed difference (table I) is much smaller. Therefore, the oxygen molecule may have preferences to approach the ends of the PFC's simply because there is more space available at the ends than in the bridgehead positions (for perfluorodecalin) or the middle of a chain (for perfluorotributylamine). Having established the characteristics of enhanced F-19 relaxation due to molecular oxygen, we can foresee the
1931
possibility of using F-19 NMR for in situ determination of the amount of oxygen dissolved in a PFC blood substitute in the body fluids and organs in animal or even clinical studies. This technique may offer an advantage over conventional methods of determination of total oxygen content, which cannot distinguish between oxygen bound to hemoglobin and oxygen dissolved in the PFC's when a blood substitute is administered. Acknowledgment. This work was supported by a Biomedical Research Support Grant from the Public Health Service. Helpful discussions with Drs. Sherril D. Christian and David F. Marten are acknowledged. Registry No. 02,7782-44-7;cis-perfluorodecalin,60433-11-6; trans-perfluordecalin,60433-12-7; perfluorotributylamine, 31189-7.
Excess Enthalpies of Aqueous Solutlons of Monosaccharides at 298.15 K: Pentoses and 2-Deoxy Sugars Guldo Barone, Giusepplna Caslronuovo, Dlonurlos Doucas, Vlttorlo Ella, and Carlo A. Mattla lstituto Chlmlco, Unhwslfy of Naples, 80134 Naples, ltaly (Recelved: June 10, 1982; In Flnal Form: November 29, 1982)
The heats of dilution in water of some pentoses (D-arabinose,D-lyxose, and D-ribose) and 2-deoxy sugars (2-deoxy-~-ribose, 2-deoxy-~-galactose,and 2-deoxy-~-glucose)were determined at 298.15 K. The calculated excess enthalpies were compared with those of isomeric and enantiomeric monosaccharide solutions and with those of sugar derivatives, oligosaccharides and other oxygenated compounds in water. All the excess thermodynamic properties of sugars and their derivatives show a characteristic behavior among the nonelectrolytes in water and suggest, together with other thermodynamic properties, that their aqueous solutions are ruled predominantly by solute-solvent interactions. Since new data are at present available, a refinement of the results of the Savage and Wood group contribution method is carried out. The group contributions to the second virial coefficients h" of the excess enthalpies of sugars,alcohols, ethers, and ketones in water are now recalculated and critically discussed. The differences among the isomers, which cannot be predicted by the method, are correlated with the differences in the stereochemistry of the solute molecules.
Introduction Aqueous solutions of simple polar nonelectrolytes are very interesting since many of them are components of biological fluids or very similar to the monomeric units of biological macromolecules. In the past years we developed a program on the excess thermodynamic properties of aqueous solutions of mono- and oligosaccharides and other hydroxylated In the preceding papers we dealt with the thermodynamics of these systems, discussed also in detail by Suggett6 and Franks.' Several molecular crystal structures and conformations, accurately deter(1) Barone, G.; Cacace, P.; Castronuovo, G.; Elia, V. Carbohydr. Res. 1981. 91. 101.
(2) Bkone, G.; Cacace, P.; Castronuovo, G.; Elia, V.; Iappelli, F. Carbohydr. Res. 1981,93, 11. (3) (a) Barone, G.; Bove, B.; Castronuovo, G.; Elia, V. J. Solution Chem. 1981,10, 803. (b) Barone, G.; Cacace, P.; Castronuovo, G.; Elia, V. Carbohydr. Res., in press. (4) Barone, G.; Cacace, P.; Castronuovo, G.; Elia, V. Gazz. Chim. Ztal. 1982,112, 153. (5) Barone, G.; Cacace, P.; Castronuovo, G.; Elia, V.; Lepore, U. Car-
bohydr. Res., in press. (6)Suggett, A. In "Water: A Comprehensive Treatise"; Franks, F., Ed.; Plenum Press: New York, 1975; Vol. IV. (7) (a) Franks, F. Phil. Trans. R. SOC.London, Ser. B 1977,278, 33. (b) fianks,F. In 'Polysaccharides in Food"; B h h a r d , J. M. V., Mitchell, J. R., Ed.; Butterworths: London, 1974; Chapter 3.
0022-365418312087-1931$01.5010
mined by means of X-ray and neutron diffraction studies, have been recently reviewed.8 The conformational problems are the subject of periodic reviews.+'l The hydration and its relation with conformation has been monitored by NMR,12or by combining NMR and dielectric rela~ation.'~Chirooptic methods have also been applied to study anomeric equilibria and mutarotation kinetics.'"'' (8) Jeffrey, G. A,; Sundaralingam, M. Adv. Carbohydr. Chem. Biochem. 1981,38,417. (9) (a) Angyal, S. J. Angew. Chem., int. Edit. Engl. 1969, 8, 157. (b) Adv. Chem. Ser. 1973, No. 117, 106. (10) Altona, C.; Haasnot, C. A. G. Org. Magn. Reson. 1980, 13, 417. (11) Gorin, P. A. J. Adu. Carbohydr. Chem. Biochem. 1981, 38, 13. (12) (a) Harvey, J. M.; Naftalin, R. J.; Symons, M. C. R. Nature (London) 1976,261,435. (b) Harvey, J. M.; Symons, M. C. R. J. Solution Chem. 1978, 7, 571. (c) Bociek, S.; Franks, F. J . Chem. SOC.,Faraday Trans. I 1979, 75, 262. (13) (a) Tait, M. J.; Suggett, A.; Franks, F.; Ablett, S.; Quickenden, P. A. J. Solution Chem. 1972, I , 131. (b) Franks, F.; Reid, D. S.; Suggett, A. J.Solution Chem. 1973,2,99. (c) Suggett, A.; Clark, A. H. J. Solution Chem. 1976, 5, 1. (d) Suggett, A.; Ablett, S; Lillford, P. J. J. Solution Chem. 1976, 5, 17. (e) Suggett, A. J. Solution Chem. 1976, 5, 33. (14) (a) Rees, D. A.; J. Chem. SOC.B 1970,877. (b) Rees, D. A,; Smith, P. J. C. J. Chem. Soc., Perkin Trans. 2 1975, 836. (15) (a) Barry, C. D.; North, A. C. T.; Glasel, J. A.; Williams, R. J. P.; Xavier, A. V. Nature (London) 1971,232,236. (b) Barry, C. D.; Martin, D. R.; Williams, R. J. P.; Xavier, A. V. J. Mol. Biol. 1974, 84, 491. (16) Dunfield, L. G.; Whittington, S. G. J. Chem. Soc., Perkin Trans. 2 1977, 654.
0 1983 American Chemical Society
