**3. X-ray structural characterization of cyclometalated Pt(II) complexes**

#### **3.1 Pt(II) complexes with 2-phenylpyridine (ppy) and its derivatives as cyclometalating ligand**

The homoleptic Pt(II) complex with 2-phenylpyridine was prepared by reacting [PtCl2(Et2S)2] with the lithiated ligand as the *cis* isomer and its crystal structure was reported in 1984 (Chassot et al., 1984).

Scheme 2. The preparation of mononuclear cyclometalated Pt(II) complexes with 2 phenylpyridine derivatives

Generally, the heteroleptic complexes are prepared by the cyclometalation of the coresponding ligand using K2PtCl4 in ethoxyethanol to give, in the first step, as a major product, the chloro-bridged dinuclear complex and, in some cases, as a minor product, the mononuclear complex having two molecules of ppy ligand. In the next step, the bridgesplitting reaction, various monodentate (L) or bidentate (A^B) ligands can be used to yield the mononuclear neutral or ionic heteroleptic complexes (see Scheme 2).  Various other R1-R3 substituents were attached on the ppy core with the aim of conferring different multifunctionalities to the resulting molecules. For instance, He et al.,

**3.1 Pt(II) complexes with 2-phenylpyridine (ppy) and its derivatives as cyclometalating**

The homoleptic Pt(II) complex with 2-phenylpyridine was prepared by reacting [PtCl2(Et2S)2] with the lithiated ligand as the *cis* isomer and its crystal structure was reported

> N N Pt Cl

R3

R1

R2

acac Na2CO3

L

A B N Pt Cl L

R1

R3

R2

R3

R2

R3

R2

N Pt A B

R1

R1

N Pt O O Y

X H/W

**3. X-ray structural characterization of cyclometalated Pt(II) complexes**

**ligand**

in 1984 (Chassot et al., 1984).

N K2PtCl4 Ethoxyethanol/H2O

R3 R3

R2 R2

phenylpyridine derivatives

N Pt Cl

R R1 R1 1

2 + R2 R3

R1=NPh2, R2=R3=H, X=Y=Me **1a** R1=R2=H,R3=-OHex, R1=-oxadiazole-4-Ph-p-NPh2, R2=R3=H, X=Y=Me **1b** A^B=5-NO2-8-quinoline **4**

R1=R2=R3=H, X=Y=Ph **1d** A^B=Et2NC(S)NCOPh **5**a

R1=R2=R3=H, L=CO **2a** A^B=MeO-4-C6H4NHC(S)NCOPh **5b**

R1=F, R2=R3=H, L=DMSO **2c** A^B=2-pyridyl hexafluoropropoxide **6** R1=F, R2=R3=H, L=py-2-Ph-4'-F **2d** R1=R2=F, R3=H, A^B=(pz)2BEt2 **7** R1=R2=F, R3=H, L=py-2-Ph-2',4'-F2 **2e** R1=R2=R3=H, A^B=(3,5-Me2pz)BH2 **8** R1=R2=F, R3=H, A^B=3,5-di-*t*Bu-catechol **3** R1=R2=R3=H, A^B=dppm, PF6- **9**  Scheme 2. The preparation of mononuclear cyclometalated Pt(II) complexes with 2-

Generally, the heteroleptic complexes are prepared by the cyclometalation of the coresponding ligand using K2PtCl4 in ethoxyethanol to give, in the first step, as a major product, the chloro-bridged dinuclear complex and, in some cases, as a minor product, the mononuclear complex having two molecules of ppy ligand. In the next step, the bridgesplitting reaction, various monodentate (L) or bidentate (A^B) ligands can be used to yield the mononuclear neutral or ionic heteroleptic complexes (see Scheme 2).  Various other R1-R3 substituents were attached on the ppy core with the aim of conferring different multifunctionalities to the resulting molecules. For instance, He et al.,

R1=-oxadiazole-4-Ph-p-NTol2, R2=R3=H, X=Y=Me **1c** R1=R2=R3=H,

R1=R2=F, R3=H, X=Y=Me, W=-(CH2)2-norbornene **1e** R1=R2=R3=H,

R1=R2=R3=H, L=DMSO **2b** R1=R2=R3=H,

2006, reported the synthesis and structural, photophysical, electrochemical, and electroluminescent properties of a novel class of trifunctional Pt(II) cyclometalated complexes incorporating the hole-transporting triarylamine, electron-transporting oxadiazole, and electroluminescent metal components into a single molecule (**1a**-**c**). Other studies focused on functionalizing the acac derivatives, as it is the example reported by Cho et al., 2007, in which the norbornene-functionalized derivative of acetylacetone has been used to synthesize a series of new polymerizable norbornene-derivatized phosphorescent platinum complexes (**1e**). For these acac Pt(II) complexes, it was found that the two Pt-O bonds are different, with the Pt-O1 trans to C atom bond longer than the Pt-O2 trans to N bond due to the strong trans influence of C-ppy donor atom (Table 1).

Several crystal structures of cyclometalated Pt(II) complexes bearing monodentate neutral ligands such as DMSO or pyridine derivatives were reported (**2a-e**). Another strategy to obtain mononuclear Pt(II) species is to use bidentate mononegative ligands and various such examples were reported so far (**3** – **8**).

By using sodium salts of N-benzoylthiourea derivatives, a series of luminescent Pt(II) ppy complexes were prepared and investigated by single-crystal X-ray diffraction (**5a**, **b**) (Figure 2).

Fig. 2. ORTEP view of complex **5a** (a); the emission spectrum of **5a** recorded in CH2Cl2 solution at room temperature (b)

An interesting feature of the structure of complex **5b** is the orientation adopted by the *p*anisyl ring of the *N*-benzoyl thiourea ligand with a twist of 65.1º with respect to the core plane, leading to the formation of weak intermolecular NH...Pt interactions (H...Pt 2.74 Å; N-H...Pt 156.8°) compared to those found in the salt (NnPr4)2[PtCl4][PtCl2(NH2Me)2]. In this case, the shortest Pt-Pt distance between two neighbouring molecules is 4.18 Å.

X-Ray Structural Characterization of Cyclometalated Luminescent Pt(II) Complexes 261

and **11c** show several interesting features such as the intermolecular Pt···Pt, π...π and C-H···π(C≡C) interactions in an orthogonal configuration. On the other hand, the crystal structure of **11a** shows the formation of dimers in a head-to-tail fashion with an interplanar distance of approximately 3.4 Å and a shortest intermetallic separation of 4.886 Å, indicating the presence of π···π interaction, but not a Pt···Pt interaction. The presence of such intermetallic interactions has a marked impact upon the solid state emission properties.

> N N Pt Cl

R1=R2=H, X=Cl **10a 12 13**

Table 2. A selection of bond lengths for some N^C^N Pt(II) complexes

Pt-N1 Pt-N2

The room temperature structureless emissions at λmax 819 (**11b**) and 702 nm (**11c**), respectively, strongly red-shifted compared to solution emission (λmax = 486 and 480, respectively), can be assigned to triplet metal-metal-to-ligand charge-transfer (3MMLCT) excited states. The photophysical properties of chloride complexes (**10a**-**c**) and analogous with various other R1 substituents were systematically studied by Farley et al., 2005. It is interesting to note that these N^C^N Pt(II) complexes show relatively shorter Pt-C distances

The C^N^N type ligands were used in the preparation of both neutral or ionic complexes

An important feature of these complexes is that the central Pt-N1 bond is shorter than the marginal Pt-N2 bond (Table 3) due to the *trans* influence of the strong field cyclometalated ligand. Two crystal structures of **14a** were determined (yellow and red polymorphs). The red colour of the latter polymorph was attributed to the Pt...Pt intermolecular interactions

than those found in C^N^N Pt(II) complexes (see comparatively Tables 2 and 3).

N N Pt Cl

F F

N N Pt X

R2 R2

R1=H, R2=Me, X=Cl **10b** R1=-C(O)OCH3, R2=H, X=Cl **10c** R1=R2=H, X=-C≡C-Ph **11a** R1=CF3, X=-C≡C-Ph **11b** R1=CF3, X=-C≡C-Ph-4-NMe2 **11c**

**3.2.2 C^N^N ligands**

(see Scheme 4).

(3.366 Å).

Scheme 3.

R1

Table 1. Selected bond lengths for compounds **1** - **9**

#### **3.2 Cyclometalated Pt(II) complexes with "pincer" ligands**

The cyclometalated Pt(II) complexes with terdentate "pincer" type ligands were investigated intensively, in part due to the fact that such ligands may provide additional rigidity to the molecule that could be responsible for favouring the luminescence properties. Many types of pincer ligands have been used in the preparation of both mono or polynuclear organometallic Pt(II) complexes and they are divided according to the donor atom set involved in bond formation with the metal centre, as follows: N^C^N, C^N^N and C^C^N complexes.

#### **3.2.1 N^C^N ligands**

Several crystal structures of N^C^N Pt(II) complexes were reported and these are summarised in Scheme 3, while the selected bond lengths are included in Table 2. The chloride Pt(II) complexes (**10a**-**c**, **12**, **13**) can be easily obtained by orthometalation reaction of the corresponding N^C^N pincer ligand with K2PtCl4 in acetic acid with high yields, while the acetylide complexes **11a-c** were prepared in quantitative yields starting from the corresponding chloride precursor, with an excess of aryl acetylene in methanol in the presence of NaOH for one day at room temperature. The crystal structures of complexes **11b**

and **11c** show several interesting features such as the intermolecular Pt···Pt, π...π and C-H···π(C≡C) interactions in an orthogonal configuration. On the other hand, the crystal structure of **11a** shows the formation of dimers in a head-to-tail fashion with an interplanar distance of approximately 3.4 Å and a shortest intermetallic separation of 4.886 Å, indicating the presence of π···π interaction, but not a Pt···Pt interaction. The presence of such intermetallic interactions has a marked impact upon the solid state emission properties.

R1=R2=H, X=-C≡C-Ph **11a** R1=CF3, X=-C≡C-Ph **11b** R1=CF3, X=-C≡C-Ph-4-NMe2 **11c**

Scheme 3.

260 Current Trends in X-Ray Crystallography

Table 1. Selected bond lengths for compounds **1** - **9**

complexes.

**3.2.1 N^C^N ligands**

**3.2 Cyclometalated Pt(II) complexes with "pincer" ligands**

The cyclometalated Pt(II) complexes with terdentate "pincer" type ligands were investigated intensively, in part due to the fact that such ligands may provide additional rigidity to the molecule that could be responsible for favouring the luminescence properties. Many types of pincer ligands have been used in the preparation of both mono or polynuclear organometallic Pt(II) complexes and they are divided according to the donor atom set involved in bond formation with the metal centre, as follows: N^C^N, C^N^N and C^C^N

Several crystal structures of N^C^N Pt(II) complexes were reported and these are summarised in Scheme 3, while the selected bond lengths are included in Table 2. The chloride Pt(II) complexes (**10a**-**c**, **12**, **13**) can be easily obtained by orthometalation reaction of the corresponding N^C^N pincer ligand with K2PtCl4 in acetic acid with high yields, while the acetylide complexes **11a-c** were prepared in quantitative yields starting from the corresponding chloride precursor, with an excess of aryl acetylene in methanol in the presence of NaOH for one day at room temperature. The crystal structures of complexes **11b**

Table 2. A selection of bond lengths for some N^C^N Pt(II) complexes

The room temperature structureless emissions at λmax 819 (**11b**) and 702 nm (**11c**), respectively, strongly red-shifted compared to solution emission (λmax = 486 and 480, respectively), can be assigned to triplet metal-metal-to-ligand charge-transfer (3MMLCT) excited states. The photophysical properties of chloride complexes (**10a**-**c**) and analogous with various other R1 substituents were systematically studied by Farley et al., 2005. It is interesting to note that these N^C^N Pt(II) complexes show relatively shorter Pt-C distances than those found in C^N^N Pt(II) complexes (see comparatively Tables 2 and 3).

#### **3.2.2 C^N^N ligands**

The C^N^N type ligands were used in the preparation of both neutral or ionic complexes (see Scheme 4).

An important feature of these complexes is that the central Pt-N1 bond is shorter than the marginal Pt-N2 bond (Table 3) due to the *trans* influence of the strong field cyclometalated ligand. Two crystal structures of **14a** were determined (yellow and red polymorphs). The red colour of the latter polymorph was attributed to the Pt...Pt intermolecular interactions (3.366 Å).

X-Ray Structural Characterization of Cyclometalated Luminescent Pt(II) Complexes 263

528 to 558 nm in acetonitrile at 298 K, which were assigned to 3MLCT excited states. Also, dinuclear phosphorescent C^N^N Pt(II) cyclometalated were prepared (also investigated by X-ray crystallography) by using diacetylide – carbazole bridging ligand (Seneclauze et al.,

The C^N^C cyclometalated Pt(II) complexes are synthesised by using K2PtCl4 and the corresponding 2,6-diphenyl-pyridine derivative, in two consecutive cyclometalation reactions. In the first step, a dinuclear chloride-bridged C^N cyclometalated Pt(II) complex is obtained, followed by reaction with a monodentate neutral ligand to give mononuclear neutral C^N^C species. Several crystallographic studies were carried out on such systems

> N Pt

N N Pt X

Pt X

S O Me Me

Complexes **19a-c** were prepared by reacting K2PtCl4 with the terdentate 2,6-di-(2'-naphthyl) pyridine ligands in glacial acetic acid, followed by heating in DMSO. Their crystal structures reveal that the molecules are paired in a head-to-tail orientation with Pt···Pt separations longer than 6.3 Å, with extensive close C−H···π (*d* = 2.656−2.891 Å) and π···π (*d* = 3.322−3.399 Å) interactions. An interesting feature of such C^N^C Pt(II) complexes is that the Pt-C bonds are longer compared to the N^C^N or N^N^C Pt(II) complexes and this is due the *trans* influence of C atoms on each other. These complexes are emissive in both solid state, with the maxima in the range 600 – 650 nm (**19a-c**), and in solution at 77 K (**18a**). Additionally, several dinuclear C^N^C cyclometalated Pt(II) complexes, either by using a dicyclometalated ligand (Zucca et al., 2006) or a diphosphine ligand as a bridge (dppm, diphenylphosphinomethane, Kui et al., 2006), were investigated by X-ray crystallography.

X=py-4-NMe2, R=H **18b** R=Ph **19b** X=3,5-Me2-py **20**

R

2007).

Fig. 3. ORTEP view of complex **14b**

N Pt X R R

and these are summarised in Scheme 5 and Table 4.

X=pz (pyrazine), R=H **18a** R=H **19a**

R=OC6H13, X=CO **18c** R=Ph-4-Br **19c**

**3.2.3 C^N^C ligands**

Scheme 5.

Table 3. Selected bond lengths for C^N^N Pt(II) complexes **14** - **17**

The chloride ligand can be easily replaced by acetylide ligands to yield various neutral Pt(II) complexes that could be investigated by X-ray crystallography. Thus, such acetylide complexes show high efficient luminescence properties due to the combination of the strong field cyclometalated ligand with the strong field acetylide ligands and the rigidity of the terdentate ligands. Important, their emission properties could be tuned by varying either R1 substituent on the C^N^N ligand or the acetylide ligand and several studies were reported on this topic (Lu et al., 2004). A series of luminescent cyclometalated platinum(II) diaminocarbene complexes (**17a-d**) were prepared by nucleophilic attack of amines at the coordinated isocyanide ligands of [(C^N^N)PtC≡NR]+ (R = *t*Bu or Ar). Weak π...π stacking interactions between the cyclometalated ligands were observed in the crystal lattice (range 3.5−3.6 Å). These complexes, **17a-d,** show structureless emissions, with λmax ranging from 528 to 558 nm in acetonitrile at 298 K, which were assigned to 3MLCT excited states. Also, dinuclear phosphorescent C^N^N Pt(II) cyclometalated were prepared (also investigated by X-ray crystallography) by using diacetylide – carbazole bridging ligand (Seneclauze et al., 2007).

#### Fig. 3. ORTEP view of complex **14b**

#### **3.2.3 C^N^C ligands**

262 Current Trends in X-Ray Crystallography

N N Pt

HN N R2 R3 C H

R1

+

A-

N N Pt X

Scheme 4.

 Selected bond lengths for C^N^N Pt(II) complexes **14** - **17**

The chloride ligand can be easily replaced by acetylide ligands to yield various neutral Pt(II) complexes that could be investigated by X-ray crystallography. Thus, such acetylide complexes show high efficient luminescence properties due to the combination of the strong field cyclometalated ligand with the strong field acetylide ligands and the rigidity of the terdentate ligands. Important, their emission properties could be tuned by varying either R1 substituent on the C^N^N ligand or the acetylide ligand and several studies were reported on this topic (Lu et al., 2004). A series of luminescent cyclometalated platinum(II) diaminocarbene complexes (**17a-d**) were prepared by nucleophilic attack of amines at the coordinated isocyanide ligands of [(C^N^N)PtC≡NR]+ (R = *t*Bu or Ar). Weak π...π stacking interactions between the cyclometalated ligands were observed in the crystal lattice (range 3.5−3.6 Å). These complexes, **17a-d,** show structureless emissions, with λmax ranging from

R1

The C^N^C cyclometalated Pt(II) complexes are synthesised by using K2PtCl4 and the corresponding 2,6-diphenyl-pyridine derivative, in two consecutive cyclometalation reactions. In the first step, a dinuclear chloride-bridged C^N cyclometalated Pt(II) complex is obtained, followed by reaction with a monodentate neutral ligand to give mononuclear neutral C^N^C species. Several crystallographic studies were carried out on such systems and these are summarised in Scheme 5 and Table 4.

Scheme 5.

Complexes **19a-c** were prepared by reacting K2PtCl4 with the terdentate 2,6-di-(2'-naphthyl) pyridine ligands in glacial acetic acid, followed by heating in DMSO. Their crystal structures reveal that the molecules are paired in a head-to-tail orientation with Pt···Pt separations longer than 6.3 Å, with extensive close C−H···π (*d* = 2.656−2.891 Å) and π···π (*d* = 3.322−3.399 Å) interactions. An interesting feature of such C^N^C Pt(II) complexes is that the Pt-C bonds are longer compared to the N^C^N or N^N^C Pt(II) complexes and this is due the *trans* influence of C atoms on each other. These complexes are emissive in both solid state, with the maxima in the range 600 – 650 nm (**19a-c**), and in solution at 77 K (**18a**). Additionally, several dinuclear C^N^C cyclometalated Pt(II) complexes, either by using a dicyclometalated ligand (Zucca et al., 2006) or a diphosphine ligand as a bridge (dppm, diphenylphosphinomethane, Kui et al., 2006), were investigated by X-ray crystallography.

X-Ray Structural Characterization of Cyclometalated Luminescent Pt(II) Complexes 265

Another interesting group of cyclometalated Pt(II) complexes bearing benzoquinolinate ligand is represented by those complexes containing isocyanide ligands. They have been found to show interesting photophysical properties, including low-energy emissions in fluid solution, depending on either the counteranion, isocyanide (CNR) ligand or crystal packing. Diez et al. recently reported the X-ray crystal structures of the isocyanide benzoquinolate Pt(II)

> - , PF6

Bu 9, 2-Np 10), where Xyl=2,6-dimethyl-phenyl or xylyl and Np = naphtyl. It was

CHCl3]∞ (**27a)**, and a yellow form which consists of discrete dimers,

counteranion and concentration on their luminescent properties (Diez et al., 2009a). The crystal packing of the two complexes containing the cation [Pt(bzq)(CN-Xyl)2]+ and different counteranions (**25a** and **25b**) was found to show significant differences, although in both cases π...π intermolecular interactions are present. The same authors (Diez et al., 2010a) reported the crystal structures and the photophysical properties of the neutral complexes [Pt(bzq)Cl(CNR)]

found that compound **26** forms only yellow crystals in which two monomers are weakly contacting through π...π (bzq) interactions. The complex **27** with tert-butylisocyanide ligand shows solid-state pseudopolymorphic behaviour. Thus, two X-ray structures are reported: a red form, which exhibits an infinite 1-D chain network, including a molecule of chloroform as

0.5H2O]2 (**27b)**. The crystal packing of these two forms is stabilised by short Pt...Pt distances and π...π (bzq) interplanar bonding interactions. Indeed, the extended 1D-chain of **27a** exhibits equivalent Pt(II)-Pt(II) distances of 3.3547(2) Å and a nearly linear Pt...Pt...Pt angle [169.12(2)°],

When the 2-naphthylisocyanide ligand was employed, again, two isomeric species have been isolated, a neutral yellow derivative, which crystallizes as a Pt...Pt dimer,

Another category of ancillary ligands widely used in the preparation of cyclometalated Pt(II) benzoquinolinate complexes are the phosphine ligands, both in mono and bidentate form. The simplest one is the neutral complex **29** in which the diphenylphosphine (PHPh2) ligand is bound to the platinum center while the coordination sphere is completed with a chloride anion. It is interesting that when the [Pt(bzq)(μ-Cl)]2 was reacted with PHPh2 and excess of

[Pt(bzq)Cl(CN-2-Np)]2 (**28a**), and a double salt [Pt(bzq)(CN-2-Np)2]+[Pt(bzq)Cl2]-

NEt3, then a phosphide-bridge platinum dimer [Pt(bzq)(μ-PPh2)]2 (**30)** was obtained.

(**28b**).

complexes [Pt(bzq)(CNR)2]X (R = Xyl, X = ClO4

thus indicating some degree of Pt...Pt interactions along the chain.

(R= Xyl, 8, t

[**27**.

crystallizing solvent, [**27**.

Fig. 4. ORTEP view of complex **23**

Table 4. Selected bond lengths for C^N^C Pt(II) compounds **18** - **20**

#### **3.3 Pt(II) complexes with benzo(h)quinoline (bzq) as cyclometalating ligand**

The homoleptic Pt(II) complex with benzo(h)quinoline was prepared by reacting [PtCl2(Et2S)2] with the lithiated ligand, its crystal structure being reported in 1996 (Jolliet et al., 1996). It was found that the crystal structure shows an important distortion from the square planar geometry towards a two-bladed helix with average Pt–C and Pt–N distances being 1.988 and 2.151 Å, respectively.

Scheme 6. Heteroleptic cyclometalated Pt(II) complexes containing the benzo(h)quinoline ligand

Various heteroleptic cyclometalated Pt(II) complexes either ionic or neutral were synthesized starting from the binuclear μ-chloro bridged complex, and analysed through single-crystal X-ray diffraction. They are summarised in Scheme 6 and their crystallographic data are included in Table 5.

An interesting example showing how the Pt...M interactions affect the photoluminescence properties for such complexes bearing the cyclometalated bzq together with acetylide ligands is represented by complex **23**, whose molecular structure is depicted in Figure 4, which has very short PtII...PbII (2.9758(5) and 2.9182(5) Å) and Pt...Pt distances (3.579 Å). For this complex, the emissive state in solid state (77 K) is attributed to a 3MLM′CT [Pt(1)π(C≡CPh)→Pt(2)/Pb(sp)π\*(C≡CPh)] state mixed with some ππ\* excimeric character.

Table 4. Selected bond lengths for C^N^C Pt(II) compounds **18** - **20**

being 1.988 and 2.151 Å, respectively.

X=Y=-C≡C-Ph, Kat=NBu4+ **21** X=Y=PPh2 **30** X=Y=-C≡C-Py-2, Kat=NBu4+ **22** X=Y=dppm, PF6- **31a** X=Y=-C≡C-Ph, Kat=Pb2+ **23** X=Y=dppe, A=PF6- **31b** X=-C≡C-Ph, Y=PPh2(C≡CPh) **24** X=Y=dppp, A=PF6- **31c** X=Y=-C≡N-Xyl, A=ClO4- **25a** X=dppm, Y=4-Tol, Tol=tolyl **32**

X=Y=-C≡N-Xyl, A=PF6- **25b** X=DMSO, Y=Cl **33a** X=-C≡N-Xyl, Y=Cl **26** X=4-MeO-Py, Y=Cl **33b** X=-C≡N-*t*Bu, Y=Cl **27** X=SMe2, Y=4-Tol **34** X=-C≡N-2-Np, Y=Cl, Np=Naphtyl **28** X=Y=[9]aneS3,

X=PHPh2, Y=Cl **29** 1,4,7-trithiacyclononane, A=PF6- **35**

Scheme 6. Heteroleptic cyclometalated Pt(II) complexes containing the benzo(h)quinoline

Various heteroleptic cyclometalated Pt(II) complexes either ionic or neutral were synthesized starting from the binuclear μ-chloro bridged complex, and analysed through single-crystal X-ray diffraction. They are summarised in Scheme 6 and their crystallographic

An interesting example showing how the Pt...M interactions affect the photoluminescence properties for such complexes bearing the cyclometalated bzq together with acetylide ligands is represented by complex **23**, whose molecular structure is depicted in Figure 4, which has very short PtII...PbII (2.9758(5) and 2.9182(5) Å) and Pt...Pt distances (3.579 Å). For this complex, the emissive state in solid state (77 K) is attributed to a 3MLM′CT [Pt(1)π(C≡CPh)→Pt(2)/Pb(sp)π\*(C≡CPh)] state mixed with some ππ\* excimeric character.

N Pt X Y

X=Y=2-pyridyl hexafluoropropoxide **36**

data are included in Table 5.

ligand

**3.3 Pt(II) complexes with benzo(h)quinoline (bzq) as cyclometalating ligand**

The homoleptic Pt(II) complex with benzo(h)quinoline was prepared by reacting [PtCl2(Et2S)2] with the lithiated ligand, its crystal structure being reported in 1996 (Jolliet et al., 1996). It was found that the crystal structure shows an important distortion from the square planar geometry towards a two-bladed helix with average Pt–C and Pt–N distances

> N Pt X Y

\_

Kat+

N Pt X Y +

A-

Another interesting group of cyclometalated Pt(II) complexes bearing benzoquinolinate ligand is represented by those complexes containing isocyanide ligands. They have been found to show interesting photophysical properties, including low-energy emissions in fluid solution, depending on either the counteranion, isocyanide (CNR) ligand or crystal packing. Diez et al. recently reported the X-ray crystal structures of the isocyanide benzoquinolate Pt(II) complexes [Pt(bzq)(CNR)2]X (R = Xyl, X = ClO4 - , PF6 -, **25a,b**) as well as the influence of the counteranion and concentration on their luminescent properties (Diez et al., 2009a). The crystal packing of the two complexes containing the cation [Pt(bzq)(CN-Xyl)2]+ and different counteranions (**25a** and **25b**) was found to show significant differences, although in both cases π...π intermolecular interactions are present. The same authors (Diez et al., 2010a) reported the crystal structures and the photophysical properties of the neutral complexes [Pt(bzq)Cl(CNR)] (R= Xyl, 8, t Bu 9, 2-Np 10), where Xyl=2,6-dimethyl-phenyl or xylyl and Np = naphtyl. It was found that compound **26** forms only yellow crystals in which two monomers are weakly contacting through π...π (bzq) interactions. The complex **27** with tert-butylisocyanide ligand shows solid-state pseudopolymorphic behaviour. Thus, two X-ray structures are reported: a red form, which exhibits an infinite 1-D chain network, including a molecule of chloroform as crystallizing solvent, [**27**. CHCl3]∞ (**27a)**, and a yellow form which consists of discrete dimers, [**27**. 0.5H2O]2 (**27b)**. The crystal packing of these two forms is stabilised by short Pt...Pt distances and π...π (bzq) interplanar bonding interactions. Indeed, the extended 1D-chain of **27a** exhibits equivalent Pt(II)-Pt(II) distances of 3.3547(2) Å and a nearly linear Pt...Pt...Pt angle [169.12(2)°], thus indicating some degree of Pt...Pt interactions along the chain.

Fig. 4. ORTEP view of complex **23**

When the 2-naphthylisocyanide ligand was employed, again, two isomeric species have been isolated, a neutral yellow derivative, which crystallizes as a Pt...Pt dimer, [Pt(bzq)Cl(CN-2-Np)]2 (**28a**), and a double salt [Pt(bzq)(CN-2-Np)2]+[Pt(bzq)Cl2]- (**28b**). Another category of ancillary ligands widely used in the preparation of cyclometalated Pt(II) benzoquinolinate complexes are the phosphine ligands, both in mono and bidentate form. The simplest one is the neutral complex **29** in which the diphenylphosphine (PHPh2) ligand is bound to the platinum center while the coordination sphere is completed with a chloride anion. It is interesting that when the [Pt(bzq)(μ-Cl)]2 was reacted with PHPh2 and excess of NEt3, then a phosphide-bridge platinum dimer [Pt(bzq)(μ-PPh2)]2 (**30)** was obtained.

X-Ray Structural Characterization of Cyclometalated Luminescent Pt(II) Complexes 267

the different *trans* influence of the C and N atoms of the cyclometalated ligands, with Pt-S

Interestingly, complex **36** bearing chelating 2-pyridyl hexafluoropropoxide ancillary ligand shows evidence for the occurrence of π...π stacking between the cyclometalated ligands, but a lack of intermolecular Pt...Pt interaction. The π...π stacking was also confirmed by the observation of additional large Stokes shifted emission attributed to the aggregated

Although various cyclometalated Pt(II) species are intensively studied for their luminescent properties, surprisingly, almost no attention was given so far to the luminescent cycloplatinated imino species. It is almost very recent that these types of complexes started to be investigated for their photophysical properties as well (Scaffidi-Domianello et al., 2007).

> NH Pt Cl S O R R

Scheme 7. Cyclometalated Pt(II) complex with benzophenone imine ligands. R = Me, (**37a**), (Pt-C = 2.006(9)Å, Pt-N = 2.019(6)Å, Pt – S = 2.215(2)Å, Pt – Cl = 2.392(2)Å); R = (CH2)4,

In **37a**, the asymmetric unit contains two independent Pt complexes, while in **37b**, it includes four Pt complexes linked by the intermolecular hydrogen-bonding network between the NH group and Cl atoms (Figure 5). The Pt – X distances for only one molecule are indicated in Scheme 7. There is no significant Pt...Pt interactions in the solid state. The two Pt(II) complexes show an emission band with the maximum located at 535 nm, along with another less intense emission at 565 nm. The solution quantum yields of the complexes

Fig. 5. The hydrogen bonding network connecting four independent molecules in the unit

cell of **37b** (this figure was generated by using the Mercury 2.2 software)

(**37b**), (Pt-C = 2.016(4)Å, Pt-N = 2.019(4)Å, Pt – S = 2.2063(13)Å, Pt – Cl =

2.3925(11)Å)(Scaffidi-Domianello et al., 2007)

are rather low, with values smaller than 0.0071.

trans to C atom longer than the Pt-S trans to N atom.

**3.4 Cyclometalated Pt(II) complexes with imine ligands**

counterparts in solid thin film.

Table 5. Crystallographic data of the cyclometalated Pt(II) complexes containing benzoquinoline ligand

A series of cyclometalated Pt(II) complexes with several bidentate bis-diphenylphosphine ligands where the bridge length between the two phosphine units was varied (bisdiphenylphosphinomethane (dppm), bis-diphenylphosphinoethane (dppe) and bisdiphenylphosphinopropane (dppp), respectively, **31a-c**) were prepared and investigated structurally by DePriest et al., 1997. These complexes are a beautiful examples where the C and N atoms can be distinguished based on their different *trans* influence: the anionic C is a better σ-donor and thus, has a greater *trans* influence compared to N atom. This difference can be easily seen in the Pt-P bond lengths, with the Pt-P *trans* to C atom bond being longer than Pt-P trans to N atom bond. All these complexes show emission properties in solution (ethanol/methanol = 4/1, v/v) at low temperatures (77 – 180 K), assigned to ligand-centred (LC) transitions.

Several other cycloplatinated clusters containing bridged phosphine or phosphido ligands have been prepared. If the neutral binuclear phosphido complex [Pt(bzq)(μ-PPh2)]2 (**30**) reacts with cis-[Pt(C6F5)2(thf)2] in CH2Cl2 at 1:2 molar ratio, then a bent neutral triplatinum cluster [Pt3(bzq)(μ-PPh2)2(C6F5)3] can be isolated. Its crystal structure was reported by Diez et al, 2006. The crystal structure of complex **35** reveals the two different Pt-S bonds due to the different *trans* influence of the C and N atoms of the cyclometalated ligands, with Pt-S trans to C atom longer than the Pt-S trans to N atom.

Interestingly, complex **36** bearing chelating 2-pyridyl hexafluoropropoxide ancillary ligand shows evidence for the occurrence of π...π stacking between the cyclometalated ligands, but a lack of intermolecular Pt...Pt interaction. The π...π stacking was also confirmed by the observation of additional large Stokes shifted emission attributed to the aggregated counterparts in solid thin film.

#### **3.4 Cyclometalated Pt(II) complexes with imine ligands**

266 Current Trends in X-Ray Crystallography

Table 5. Crystallographic data of the cyclometalated Pt(II) complexes containing

A series of cyclometalated Pt(II) complexes with several bidentate bis-diphenylphosphine ligands where the bridge length between the two phosphine units was varied (bisdiphenylphosphinomethane (dppm), bis-diphenylphosphinoethane (dppe) and bisdiphenylphosphinopropane (dppp), respectively, **31a-c**) were prepared and investigated structurally by DePriest et al., 1997. These complexes are a beautiful examples where the C and N atoms can be distinguished based on their different *trans* influence: the anionic C is a better σ-donor and thus, has a greater *trans* influence compared to N atom. This difference can be easily seen in the Pt-P bond lengths, with the Pt-P *trans* to C atom bond being longer than Pt-P trans to N atom bond. All these complexes show emission properties in solution (ethanol/methanol = 4/1, v/v) at low temperatures (77 – 180 K), assigned to ligand-centred

Several other cycloplatinated clusters containing bridged phosphine or phosphido ligands have been prepared. If the neutral binuclear phosphido complex [Pt(bzq)(μ-PPh2)]2 (**30**) reacts with cis-[Pt(C6F5)2(thf)2] in CH2Cl2 at 1:2 molar ratio, then a bent neutral triplatinum cluster [Pt3(bzq)(μ-PPh2)2(C6F5)3] can be isolated. Its crystal structure was reported by Diez et al, 2006. The crystal structure of complex **35** reveals the two different Pt-S bonds due to

benzoquinoline ligand

(LC) transitions.

Although various cyclometalated Pt(II) species are intensively studied for their luminescent properties, surprisingly, almost no attention was given so far to the luminescent cycloplatinated imino species. It is almost very recent that these types of complexes started to be investigated for their photophysical properties as well (Scaffidi-Domianello et al., 2007).

Scheme 7. Cyclometalated Pt(II) complex with benzophenone imine ligands. R = Me, (**37a**), (Pt-C = 2.006(9)Å, Pt-N = 2.019(6)Å, Pt – S = 2.215(2)Å, Pt – Cl = 2.392(2)Å); R = (CH2)4, (**37b**), (Pt-C = 2.016(4)Å, Pt-N = 2.019(4)Å, Pt – S = 2.2063(13)Å, Pt – Cl = 2.3925(11)Å)(Scaffidi-Domianello et al., 2007)

In **37a**, the asymmetric unit contains two independent Pt complexes, while in **37b**, it includes four Pt complexes linked by the intermolecular hydrogen-bonding network between the NH group and Cl atoms (Figure 5). The Pt – X distances for only one molecule are indicated in Scheme 7. There is no significant Pt...Pt interactions in the solid state. The two Pt(II) complexes show an emission band with the maximum located at 535 nm, along with another less intense emission at 565 nm. The solution quantum yields of the complexes are rather low, with values smaller than 0.0071.

Fig. 5. The hydrogen bonding network connecting four independent molecules in the unit cell of **37b** (this figure was generated by using the Mercury 2.2 software)

X-Ray Structural Characterization of Cyclometalated Luminescent Pt(II) Complexes 269

The relevant Pt(II) systems bearing terdentate imine ligands are shown in Scheme 9. The cyclometalated Pt(II) complexes with thiosemicarbazone ligands were included here. The crystal structures of such complexes with terdentate imines reveal a strong *trans* influence of the carbon donor ligands. For instance, in complex **47**, the Pt–NMe2 bond length of 2.162(14) Å is longer than the imine Pt–N bond length of 2.04(2) Å as a consequence of *trans* aryl group which has a high *trans* influence. On the other hand, for such complexes, the longer Pt–N bond is also consistent with the weaker ligating ability of tertiary amines for platinum. The Pt–C bond lengths are found to be in the expected range. It is interesting to note that the complex **52** represents the first luminescent platinum(II) compound with a [C^N^S] terdentate ligand. The long intermolecular S...S distance precludes the existence of any direct interaction between these atoms. Also, the Pt...Pt distance between neighbouring molecules is 4.216(3) Å which is larger, for instance, than the values reported for related platinacycles having [C(sp2)^N^N]- and [C(sp2)^N^S]- terdentate ligands from the "pincer" family. The emission spectrum of this compound recorded at 298K in CH2Cl2 solution shows a maximum at 578 nm when excited at 388 nm with no additional information regarding the quantum yield and lifetime provided. For the rest of complexes (**43** – **51**), no data regarding the luminescence properties were reported. Interestingly, the thiosemicarbazone ligands can be used in cycloplatination reaction to give orthometalated complexes in which the ligand acts as terdentate through the C, N and S atoms and two such examples are presented in Scheme 9 (**53a** and **53b**). **53a** was obtained by bridge-cleavage with PPh3 of the first Pt(II) cyclometalated tetranuclear complexes bearing thiosemicarbazone ligands which were

> N Pt L

R'

X=Y =W=Z=H, L=Ph **43** L=Cl, R=Et, R'=H, n = 1 **50** (Riera et al., 2000)

N Pt L

Me

X=NO2, R=Me, L=thiosemicarbazone **53b**

X

N S

NHR

X=Y=W=Z=H, L=Br **44** L=Cl, R=Me, R'=COOMe, n =2 **51**

(CH2)n SR

**3.4.2 Cyclometalated Pt(II) complexes with terdentate imine ligands**

prepared using K2PtCl4 as starting material.

N Pt L X Y W z

X=Z=W=F, Y=H, L=Cl **45** X=Y=Z=F, W=H, L=Me **46** X=W=H, Y=Me, Z=OMe, L=Me **47** X=Ph, Y=W=Z=H, L=Me **48a** X=Ph, Y=W=Z=H, L=Cl **48b** X=Y=W=H, Z=Cl, L=4-Tol **49**

NMe2

> N Pt Cl S Me

Scheme 9. Pt(II) complexes with terdentate imine ligands

 **52** X=Me, R=H, L=PPh3 **53a**

The solid-state emission spectra for these complexes show emission maxima at 571 and 559 nm, respectively. These two complexes also exhibit some structure of the emission bands with high and low energy shoulders at 542 and 624 nm and at 525 and 610 nm, respectively.The excited-state emission lifetimes at 575 nm are in the range of 320-615 ns, consistent with the phosphorescence emissive mechanism.

#### **3.4.1 Cyclometalated Pt(II) complexes with N-Benzylidenebenzylamine ligands**

This class of cycloplatinated complexes was intensively investigated, but almost for mechanistic studies and not for emission properties. The most representative structural types are presented in Scheme 8.

Scheme 8. Pt(II) compexes with N-benzylidenebenzylamine ligands

These complexes were prepared by reacting [Pt2Me4(μ-SMe2)2] with the imine ligand in the presence of sodium acetate followed by the exchange reaction with PPh3 ligand. They were studied intesively from the cycloplatination reaction mechanism point of view and none of them were investigated for their potential luminescent properties.

The stacked structures are well-known for platinum complexes, and they become increasingly favoured with increasing aromatic core. Despite the presence of biphenyl unit in complexes **39a,b**, no significant π...π interactions have been found for these compounds.

Table 6. Selected bond lengths for cyclometalated Pt(II) complexes containing Nbenzylidenebenzylamine

#### **3.4.2 Cyclometalated Pt(II) complexes with terdentate imine ligands**

The relevant Pt(II) systems bearing terdentate imine ligands are shown in Scheme 9. The cyclometalated Pt(II) complexes with thiosemicarbazone ligands were included here. The crystal structures of such complexes with terdentate imines reveal a strong *trans* influence of the carbon donor ligands. For instance, in complex **47**, the Pt–NMe2 bond length of 2.162(14) Å is longer than the imine Pt–N bond length of 2.04(2) Å as a consequence of *trans* aryl group which has a high *trans* influence. On the other hand, for such complexes, the longer Pt–N bond is also consistent with the weaker ligating ability of tertiary amines for platinum. The Pt–C bond lengths are found to be in the expected range. It is interesting to note that the complex **52** represents the first luminescent platinum(II) compound with a [C^N^S] terdentate ligand. The long intermolecular S...S distance precludes the existence of any direct interaction between these atoms. Also, the Pt...Pt distance between neighbouring molecules is 4.216(3) Å which is larger, for instance, than the values reported for related platinacycles having [C(sp2)^N^N]- and [C(sp2)^N^S]- terdentate ligands from the "pincer" family. The emission spectrum of this compound recorded at 298K in CH2Cl2 solution shows a maximum at 578 nm when excited at 388 nm with no additional information regarding the quantum yield and lifetime provided. For the rest of complexes (**43** – **51**), no data regarding the luminescence properties were reported. Interestingly, the thiosemicarbazone ligands can be used in cycloplatination reaction to give orthometalated complexes in which the ligand acts as terdentate through the C, N and S atoms and two such examples are presented in Scheme 9 (**53a** and **53b**). **53a** was obtained by bridge-cleavage with PPh3 of the first Pt(II) cyclometalated tetranuclear complexes bearing thiosemicarbazone ligands which were prepared using K2PtCl4 as starting material.

268 Current Trends in X-Ray Crystallography

The solid-state emission spectra for these complexes show emission maxima at 571 and 559 nm, respectively. These two complexes also exhibit some structure of the emission bands with high and low energy shoulders at 542 and 624 nm and at 525 and 610 nm, respectively.The excited-state emission lifetimes at 575 nm are in the range of 320-615 ns,

This class of cycloplatinated complexes was intensively investigated, but almost for mechanistic studies and not for emission properties. The most representative structural

These complexes were prepared by reacting [Pt2Me4(μ-SMe2)2] with the imine ligand in the presence of sodium acetate followed by the exchange reaction with PPh3 ligand. They were studied intesively from the cycloplatination reaction mechanism point of view and none of

The stacked structures are well-known for platinum complexes, and they become increasingly favoured with increasing aromatic core. Despite the presence of biphenyl unit in complexes **39a,b**, no significant π...π interactions have been found for these compounds.

Table 6.  Pt(II) compexes with N-benzylidenebenzylamine ligands

them were investigated for their potential luminescent properties.

consistent with the phosphorescence emissive mechanism.

types are presented in Scheme 8.

W

benzylidenebenzylamine

Y z X

> N Pt L PPh3

> > R

 X=Y=W=Z=H, L=Br **44** L=Cl, R=Me, R'=COOMe, n =2 **51** X=Z=W=F, Y=H, L=Cl **45** X=Y=Z=F, W=H, L=Me **46** X=W=H, Y=Me, Z=OMe, L=Me **47** X=Ph, Y=W=Z=H, L=Me **48a** X=Ph, Y=W=Z=H, L=Cl **48b** X=Y=W=H, Z=Cl, L=4-Tol **49**

N Pt L (CH2)n SR R'

X=Y =W=Z=H, L=Ph **43** L=Cl, R=Et, R'=H, n = 1 **50** (Riera et al., 2000)

Scheme 9. Pt(II) complexes with terdentate imine ligands

X-Ray Structural Characterization of Cyclometalated Luminescent Pt(II) Complexes 271

Several crystallographic studies concerning the cycloplatinated complexes with bis(imine) ligands (where the N atom is not part of a ring) were reported (see Scheme 11). Complex **55** was prepared by reacting LiC≡CSiMe3 in THF with the first platinum(II) halide compounds

On the other hand, complex **56** represents the first X-ray crystal structure of stable transarylplatinum methyl complexes [PtMeN^C^N] with imine-type ligands. It is well-known that due to the strong C(sp2)−C(sp3) bond, only very few transition-metal compounds having an aryl as well as a methyl group bonded to the same metal atom are reported. The reason is that in such cases reductive elimination occurs. For complex **56** this reaction is prevented due to the trans disposition of the methyl and aryl groups and the rigid coplanarity of the chelate rings. Another representative example is complex **57a** that is the first chiral bis-aldimine (N^C^N)–pincer complexes. Unfortunately, there was no emission

N N R R Pt X

Table 8. Selected bond lengths for cyclometalated Pt(II) complexes with bis(imine) N^C^N

N R' Pt Cl

N Pt S

(CH2)n NMe2 Me O Me

H

Fe

R

Ph3P Fe

**3.4.5 Cyclometalated Pt(II) complexes containing ferrocene based imine ligands**  Several crystal structures of cyclometalated Pt(II) complexes containing imine ligands with

Pt-N1 Pt-N2

R=Me, R'=Ph **58** R=H, R'=-CH2CH2OH **61b** n = 0 **62a** R=H, R'=-CHMeCH2OH **59a** n = 1 **62b**

Scheme 12. Cycloplatinated complexes bearing ferrocene imine ligands

**3.4.4 Bis(imine) ligands – N^C^N pincer ligands**

containing the (N^C^N) isophtalaldimine ligands.

Pr)2Ph, X=-C≡CSiMe3 **55**

data reported for such complexes.

ferrocene fragment were reported (see Scheme 12).

N R' Pt Cl S

Me Me

R

O Fe

R=H, R'=-CH2CH2OH **61a**

R=H, R'=-CH(CHMe2)CH2OH **59b**

Pr)2Ph, X=CH3 **56** R=-CH(CH3)Ph, X=Cl **57a**

Bu, X=Cl **57b** R=Ph, X=Cl **57c**  Scheme 11.

pincer ligands

R=Me, R'=OH **60**

R=2,6-(i

R=2,6-(i

R=t

Table 7. Selected bond legths for cyclometalated Pt(II) complexes with terdentate imine ligands

On the other hand, complex **53b** was obtained by reacting the thiosemicarbazone ligand with the Pt dinuclear allyl complex [Pt(μ-Cl)(η3-C4H7)]2 in refluxing acetone, when, instead of the expected tetranuclear complex, a mononuclear cyclometalated Pt(II) complex containing two thiosemicarbazone molecules was formed. One of the molecule acts as a [C^N^S]- terdentate ligand while the second one is coordinated in a monodentate fashion through the S atom, thus completing the coordination sphere of Pt(II) metal. Bis(thiosemicarbazone) ligands were used for cycloplatination reaction and the first X-ray structure of a cyclometalated Pt(II) complex with such ligands was reported by Lopez-Torres & Mendiola, 2010. No emission properties were reported for such complexes.

#### **3.4.3 Pt(II) complexes bearing cyclometalated oxime ligands**

There are several X-ray crystallographic structures reported for a series of cycloplatinated complexes with oxime ligands (see Scheme 10). They were prepared starting from [PtCl2(RR'SO)2] and the corresponding oxime ligand. Although they show an interesting structural feature, as it is the case of complex **54b** that reveals an extremely short Pt...Pt contact of 3.337 Å, these complexes were studied mostly for mechanistic and catalytic purposes and no emission properties were investigated (Ryabov et al., 1995).

R = R' = Me (Pt-C = 1.998(4) Å, Pt-N = 2.013(3) Å, Pt – S = 2.2677(11) Å, Pt – Cl = 2.4114(11) Å), (**54a**); R = Me, R' = Ph (Pt-C = 2.010(4) Å, Pt-N = 2.010(3) Å, Pt – S = 2.2192(12) Å, Pt – Cl = 2.3806(13) Å) , (**54b**) (Ryabov et al., 2002)

Scheme 10.


*3.1. Computation of the Energy Density Factor EDF*

In accordance to Equation (11), the energy density factor results equal to 1.085. Therefore, to deliver the same amount of energy, an increase up to the 8.5% of the HCNG flowrate is required respect to the existing natural gas flowrate. Moreover, in accordance to Equation (17), a density ratio (ρH2/ρNG) of 0.099 results.


**4. Diagnosis and treatment**

is separated in three layers: the lipid layer, which protects the tear against evaporation and is secreted by Moll, Meibomian, and Zeiss glands [1]; the mucin layer produced by Manz glands, Henle crypts, and corneal and conjunctival cells—this one stays between the hydrophobic ocular surface and the hydrophilic tear film [2]; and the last and the most prevalent layer, the aque-

The most recent definition of dry eye is that it is a multifactorial disease of the tears and ocular surface, which is accompanied by ocular symptoms, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play etiological roles [4]. The inflammation of the ocular surface can be both the cause and the consequence of dry eye: dysfunction of the lacrimal glands alters the tear composition, leading to hyperosmolarity that stimulates more inflammation [5], and another factor recognized

There are several risk factors for dry eye, all of them are controversial. These are female sex, menopause therapy, omega-3 deficiency, refractive surgeries; use of some medications as antihistaminic drugs, antihypertensive drugs, diuretics, antidepressants, and others; hepatitis C; radiation therapy; Asian race; HIV and HTLV infection; chemotherapy; isotretinoic acid use; large facetectomy incisions; low humidity environments; ovarian dysfunction; and sarcoidosis [7].

This disease is actually classified into two primary categories: these are tear-deficient and evaporative categories. The tear-deficient dry eye group generally can be due to Sjogren's syndrome or non-Sjogren's syndrome. Sjogren's syndrome is an exocrinopathy in which lacrimal secretion deficiency occurs due to an autoimmune process that affects the lacrimal glands, salivary glands, and other organs of the body [8]. Non-Sjogren's syndrome is caused by lacrimal diseases or lacrimal obstruction and by reflex alterations, without autoimmune factor role. Some causes are age-related dry eye, congenital alacrima, familial dysautonomia, sarcoidosis, lymphoma, AIDS (acquired immunodeficiency disease syndrome), gland denervation, lacrimal obstruction as in pemphigus, trigeminal injury, diabetes, neurotrophic keratopathy, use of contact lenses, and motor reflex block due to VII pair injury [9, 10]. The evaporative causes of dry eye disease are due to oil deficit, lid changes, use of contact lenses, or ocular surface diseases, as allergic conjunctivitis, and some of the iatrogenic dry eye that occurs after the use

of systemic or topical medications or after surgeries or nonsurgical procedures [8, 11].

Dry eye can be also classified according to severity. One of the schemes is proposed by Delphi Panel [8, 12]. This classification in grades 1–4 (mild to severe) is based on the frequency or intensity of the dry eye symptoms and discomfort, the blurred vision and visual symptoms, conjunctival injection or redness, conjunctival staining, corneal staining, changes in the cornea and tear as in ocular surface, alterations in the glands and lids, tear film break-up time

Dry eye disease affects from 5 to 50% of population; this discrepancy is probably observed due to the absence of a consensus on the diagnosis of dry eye and the lack of standardization

ous layer, produced by Wolfring and Krause glands [3].

22 Plasma Medicine - Concepts and Clinical Applications

in dry eye pathogenesis is oxidative stress [6].

(TFBUT), and Schirmer's test values.

**3. Epidemiology**

Diagnosis is controversial, and literature shows the lack of correlation between some objective tests and symptoms; this is probably due to the difficulty in understanding dry eye pathophysiology [16].

There are some guidelines in this theme, and one of them is the American Academy of Ophthalmology that relates that dry eye diagnosis is obtained after a clinical approach that include asking the patient about exposition to dry eye risk factors and the most common symptoms and signs like redness, itching, photophobia, dryness, foreign body sensation, or pain. It is also important to ask the patient about the exposition to some kind of pollutant, if he is a smoker, if he has any systemic disease (like dermatological, allergic, or rheumatic diseases), checking the hygiene of eyelashes and eyelids, use of medications, eyedrop use, previous ocular surgeries [17], and use of a screening questionnaire as the OSDI (Ocular Surface Disease Index) [18]. The clinical history is followed by a complete ophthalmological exam, including evaluating the eyelids, skin, nerves, visual acuity, and biomicroscopy, and some specific tests like tear breakup time, tear film osmolarity determination, and ocular surface staining with fluorescein lissamine green [4]. The assessment of the tear meniscus (less than 0.35 mm is abnormal) can be performed, verifying if the blink rate is decreased and evaluate the quality of the tear (if there are mucus and debris) and corneal topography [3].

Management of dry eye disease will depend on the cause of this condition and its severity. There is currently no cure for dry eye, and any causal factors that are amenable to treatment should be treated. It includes modifications of the environment; suspension of topical or systemic medications, associated with worsening when possible; artificial tear lubrification; and eyelid hygiene [19].

Generally, the conventional treatment is the lubricants, but it does not resolve all the cases. There are a wide variety of artificial tears, like 1% sodium hyaluronate, hypotonic solutions, those that contains lipids or substances with bioadhesive properties and formulas that have substances that protects the cell's stress; but none of them has the natural tear properties [20, 21].

Other therapies are topical cyclosporine and corticosteroids [22], but these have some disadvantages such as eye irritation and ocular pressure elevation and cataract, respectively [23, 24]. In moderate cases we can also use systemic supplements with omega-3 and linoleic acids and the increased consumption of water, lacrimal occlusion, and glasses use. In severe dry eye, in addition to all these treatments, we can take another measure like systemic cholinergic agonists, systemic anti-inflammatory agents, mucolytic agents, contact lenses, correction of palpebral alterations, permanent lacrimal punctal occlusion, tarsorrhaphy, and, finally, the autologous serum tears [17].

with the production of mucin 1 by some conjunctival cells. Transforming growth factor b1 (TGF-b1) has an increased levels in the epithelium during corneal stromal repair processes; it stimulates the production of collagen, fibronectin, and proteoglycans and together with the platelet-derived growth factor (PDGF) has an important anti-inflammatory action [49]. Vitamin A is one of the major epitheliotropic factors in autologous serum; it is 100 times more

The Use of Platelet-Rich Plasma in Dry Eye Disease http://dx.doi.org/10.5772/intechopen.76090 25

Fibronectin is an important protein to corneal reepithelization, promoting healing and phagocytosis [51]. Annexin A5 has been investigated as an alternative to fibronectin eyedrops. It interacts with some integrins and stimulates the secretion of plasminogen activator-type urokinase, whose expression is increased in epithelial defects. Albumin is one of the most important proteins in the blood. It reduces the natural degradation of cytokines and growth factors in areas of tissue injury and shows antiapoptopic activity [39, 52, 53]. Alpha-2-macroglobulin neutralizes proteolytic enzymes. It is useful in ocular burns and marginal ulcers [32, 39]. Fibroblast growth factor-beta is a factor that promotes corneal healing, increasing cell prolif-

The insulin-like growth factor helps epithelial cell migration [55]. Neural growth factor (NGF) is the most well-known neurotrophin. It restores the function of injured neurons and can be

One of the PRP advantages is that it has not cytokines derived from leucocytes and monocytes, which are present in autologous serum and can be deleterious in patients with immune diseases [57]. PRP also regulates expression of several genes in the cellular differentiation improving biological activity of the corneal epithelial cells when compared with autologous serum [58]. The PRP protects the ocular surface from scar formation more than autologous serum, because of reduction of myofibroblasts. It has been observed in PRK where patients who had done this surgery has a decreased incidence of haze [59]. PRP causes reduction in inflammation by indirect action, through the reduction of osmolarity, thus, diluting the pro-inflammatory factors existing in the ocular surface. This also occurs because of the presence of the growth factorrich plasma interleukin-1 receptor antagonist as well as the presence of metalloproteinase [60]. Platelets have a lot of important functions that are repairing tissue damage; coagulation prevents blood loss, secreting proteins, cytokines, and other mediators; inducing tissue regeneration by cell migration, proliferation, and angiogenesis, and preventing infections because of

its antibiotic action. They also have an anti-inflammatory and analgesic action [61].

Platelet-rich plasma has been used in several medical and dental areas. The platelet-rich plasma has approximately 1 million/ml platelets [62], and it has been used to the revitalization of necrotic pulp teeth [63], in periodontitis [64], in revascularization of young teeth [65],

Platelet-rich plasma has been used in orthopedic therapies like cartilage repair [67], also in

bone regeneration, and in tendons, ligaments, and articular lesions [68].

**5. The use of PRP in medicine and odontology**

concentrated than in natural tear and prevents squamous epithelial metaplasia [50].

eration and motility [54].

effective in trophic ulcers [56].

and in other oral conditions [66].

The Ebers Papyrus 1534 BC is the first reference in the history of a blood derivative in the eye. In 1975, Ralph et al. used it in dry eye [25]. Fox et al. and later Tsubota related the use of autologous serum as an alternative treatment of severe dry eye cases [26, 27]. During many years of study, fetal bovine serum, allogenic serum, and umbilical cord serum have been used; however, they are heterologous, the risks of infections or allergic reactions are increased, and their use is not possible in any center [28]. It does not have preservative, and it is rich in vitamins, fibronectin, growth factors, and cytokines and has biomechanical properties similar to natural tear film, and they do not have preservative which is common in artificial tears [29]. Epidermal growth factors and vitamin A are important for proliferation, differentiation, and maturation of the ocular surface epithelium [30]. Fibroblast growth factor-beta is also involved in epithelial healing, fibronectin promotes cell migration, albumin has antiapoptopic activity, alpha-2-macroglobulin has anti-collagenase action, platelet-derived growth factor promotes hepatocytes growth factor, and substance P and insulin-like growth factor aid in the migration and adhesion of epithelium to the stroma [31]. The serum also maintains intracellular ATP at acceptable levels and cell membrane integrity [32–35].

Some authors related the use of autologous serum drops in dry eye with some promisor results [35, 36].

Kojima et al. in 2005 described increased TFBUT in treated group comparing to control group (using artificial tears) [37]. Lee and Chen studied the use of autologous serum in 23 patients by 18 months and found improvements in symptoms and corneal staining pattern in approximately 75% of patients [38].

Other indications for the use of autologous serum have been the epithelial defects [39], graftversus-host disease [40], neurotrophic keratopathy [41], trabeculectomy ampoules [42], after refractive surgery [43, 44], Mooren's ulcer [45], and other keratitis [46].

Tananuvat et al., in a randomized prospective study, found that control eyes had improvement in symptoms, signs, and rose bengal staining compared with the baseline. However, some advantages neither Schirmer's test results nor tear breakup time improved in treated group [34].

Urzua et al. described in a double-blind crossover clinical trial 12 severe dry eye syndrome patients in which autologous serum treatment showed a statistically significant higher OSDI decrease (50%) versus conventional treatment (22%). There were no significant changes in objective parameters (Oxford corneal staining and TBUT) [47]. A review to evaluate autologous serum efficacy compared to lubricants, in dry eye disease, concluded that there is a great heterogeneity considering the preparation and storage of the eyedrops, as well as the adequate use of this therapy, and that new studies that standardize these items would be necessary [19].

Another alternative, platelet-rich plasma (PRP), can be used in severe dry eye. It is prepared in double centrifugation of total plasma. Some of the important growth factors this hemoderivate has are platelet-derived angiogenesis factor, platelet-derived epithelial growth factor, and platelet factor 4 [48].

The epidermal growth factor accelerates the healing process and epithelial migration in the cornea, besides stimulating the DNA synthesis of the epithelial cells, and is also associated with the production of mucin 1 by some conjunctival cells. Transforming growth factor b1 (TGF-b1) has an increased levels in the epithelium during corneal stromal repair processes; it stimulates the production of collagen, fibronectin, and proteoglycans and together with the platelet-derived growth factor (PDGF) has an important anti-inflammatory action [49]. Vitamin A is one of the major epitheliotropic factors in autologous serum; it is 100 times more concentrated than in natural tear and prevents squamous epithelial metaplasia [50].

palpebral alterations, permanent lacrimal punctal occlusion, tarsorrhaphy, and, finally, the

The Ebers Papyrus 1534 BC is the first reference in the history of a blood derivative in the eye. In 1975, Ralph et al. used it in dry eye [25]. Fox et al. and later Tsubota related the use of autologous serum as an alternative treatment of severe dry eye cases [26, 27]. During many years of study, fetal bovine serum, allogenic serum, and umbilical cord serum have been used; however, they are heterologous, the risks of infections or allergic reactions are increased, and their use is not possible in any center [28]. It does not have preservative, and it is rich in vitamins, fibronectin, growth factors, and cytokines and has biomechanical properties similar to natural tear film, and they do not have preservative which is common in artificial tears [29]. Epidermal growth factors and vitamin A are important for proliferation, differentiation, and maturation of the ocular surface epithelium [30]. Fibroblast growth factor-beta is also involved in epithelial healing, fibronectin promotes cell migration, albumin has antiapoptopic activity, alpha-2-macroglobulin has anti-collagenase action, platelet-derived growth factor promotes hepatocytes growth factor, and substance P and insulin-like growth factor aid in the migration and adhesion of epithelium to the stroma [31]. The serum also maintains intra-

Some authors related the use of autologous serum drops in dry eye with some promisor

Kojima et al. in 2005 described increased TFBUT in treated group comparing to control group (using artificial tears) [37]. Lee and Chen studied the use of autologous serum in 23 patients by 18 months and found improvements in symptoms and corneal staining pattern in approxi-

Other indications for the use of autologous serum have been the epithelial defects [39], graftversus-host disease [40], neurotrophic keratopathy [41], trabeculectomy ampoules [42], after

Tananuvat et al., in a randomized prospective study, found that control eyes had improvement in symptoms, signs, and rose bengal staining compared with the baseline. However, some advantages neither Schirmer's test results nor tear breakup time improved in treated group [34]. Urzua et al. described in a double-blind crossover clinical trial 12 severe dry eye syndrome patients in which autologous serum treatment showed a statistically significant higher OSDI decrease (50%) versus conventional treatment (22%). There were no significant changes in objective parameters (Oxford corneal staining and TBUT) [47]. A review to evaluate autologous serum efficacy compared to lubricants, in dry eye disease, concluded that there is a great heterogeneity considering the preparation and storage of the eyedrops, as well as the adequate use of this therapy, and that new studies that standardize these items would be necessary [19]. Another alternative, platelet-rich plasma (PRP), can be used in severe dry eye. It is prepared in double centrifugation of total plasma. Some of the important growth factors this hemoderivate has are platelet-derived angiogenesis factor, platelet-derived epithelial growth factor,

The epidermal growth factor accelerates the healing process and epithelial migration in the cornea, besides stimulating the DNA synthesis of the epithelial cells, and is also associated

cellular ATP at acceptable levels and cell membrane integrity [32–35].

refractive surgery [43, 44], Mooren's ulcer [45], and other keratitis [46].

autologous serum tears [17].

24 Plasma Medicine - Concepts and Clinical Applications

results [35, 36].

mately 75% of patients [38].

and platelet factor 4 [48].

Fibronectin is an important protein to corneal reepithelization, promoting healing and phagocytosis [51]. Annexin A5 has been investigated as an alternative to fibronectin eyedrops. It interacts with some integrins and stimulates the secretion of plasminogen activator-type urokinase, whose expression is increased in epithelial defects. Albumin is one of the most important proteins in the blood. It reduces the natural degradation of cytokines and growth factors in areas of tissue injury and shows antiapoptopic activity [39, 52, 53]. Alpha-2-macroglobulin neutralizes proteolytic enzymes. It is useful in ocular burns and marginal ulcers [32, 39]. Fibroblast growth factor-beta is a factor that promotes corneal healing, increasing cell proliferation and motility [54].

The insulin-like growth factor helps epithelial cell migration [55]. Neural growth factor (NGF) is the most well-known neurotrophin. It restores the function of injured neurons and can be effective in trophic ulcers [56].

One of the PRP advantages is that it has not cytokines derived from leucocytes and monocytes, which are present in autologous serum and can be deleterious in patients with immune diseases [57]. PRP also regulates expression of several genes in the cellular differentiation improving biological activity of the corneal epithelial cells when compared with autologous serum [58].

The PRP protects the ocular surface from scar formation more than autologous serum, because of reduction of myofibroblasts. It has been observed in PRK where patients who had done this surgery has a decreased incidence of haze [59]. PRP causes reduction in inflammation by indirect action, through the reduction of osmolarity, thus, diluting the pro-inflammatory factors existing in the ocular surface. This also occurs because of the presence of the growth factorrich plasma interleukin-1 receptor antagonist as well as the presence of metalloproteinase [60].

Platelets have a lot of important functions that are repairing tissue damage; coagulation prevents blood loss, secreting proteins, cytokines, and other mediators; inducing tissue regeneration by cell migration, proliferation, and angiogenesis, and preventing infections because of its antibiotic action. They also have an anti-inflammatory and analgesic action [61].


**Abstract**

At the height of M2M communications, there are many alternatives and architectures that present solutions for each case and each environment. The interoperability strategy or the combination of different solutions with adequate flexibility can be solutions to maintain a capacity for easy incorporation of new sensor nodes depending on the coverage or not of operators. In addition to interoperability strategies, this chapter presents some alternatives that include multi-hop techniques, combining different technologies. Special emphasis will be placed on low-power wide area networks systems (LoRa, Narrow Band IoT, LTE, etc.) applied in remote environments, such as nature reserves and ocean or fluvial ecosystems. An estate of art of these areas will be presented, as well as results of different development of our group.

**Keywords:** wireless sensors networks, IoT, LPWAN, multi-routing, interoperability, IoT protocols


**Meet the editor**

Michael S. Firstenberg, MD is currently an Assistant Professor of Surgery and Integrative Medicine at the Northeast Ohio Medical University and a full-time Cardiothoracic surgeon at Akron City Hospital. He was previously on the faculty at The Ohio State University where, in addition to being an active cardiac surgeon, he was active on numerous University, College, and Health

system committees. He received his Thoracic surgery training at Ohio State with additional training at The Cleveland Clinic. Michael is currently active within numerous other professional organizations and has co-authored >100 manuscripts, lectured worldwide on extra-corporeal support, and he serves on the editorial board of several Journals. He was recently nominated for the prestigious Thoracic Surgery Resident Association Socrates Teaching Award.

Contents

**Preface VII**

Chapter 1 **Anesthesia for Thoracic Surgical Procedures 3**

Norman and Ronaldo Purugganan

Chapter 3 **Postoperative Care and Complications After**

Chapter 4 **Management of Malignant Pleural Effusion 85**

Hidir Esme and Mustafa Calik

**Operative Therapies 129** Kelvin K.W. Lau and Calvin S.H. Ng

**Thoracic Surgery 57** Anand Iyer and Sumit Yadav

**Approach 109**

Ihsan Alloubi

Chapter 2 **Evolution of Surgical Approaches for Lung Resection 47** Trevor Williams and Wickii T. Vigneswaran

Chapter 5 **Superior Sulcus Tumour with some Emphasis on the Anterior**

Haralabos Parissis, Alan Soo and Bassel Al-Alao

Chapter 6 **Malignant Pleural Mesothelioma and the Role of Non–**

Chapter 7 **Recent Advances in Surgical Techniques for Multimodality Treatment of Malignant Pleural Mesothelioma 167**

Chapter 8 **Thoracic Hydatid Cyst: Clinical Presentation, Radiological Features and Surgical Treatment 195**

Christos Asteriou, Athanassios Kleontas and Nikolaos Barbetakis

January Tsai, Teresa Moon, Shital Vachhani, Javier Lasala, Peter H

**Section 1 Thoracic Surgery 1**


# **Organic and Hybrid Materials for Photovoltaic and Photonic Applications**

Edited by Tersilla Virgili and Mariacecilia Pasini Printed Edition of the Special Issue Published in *Molecules*

www.mdpi.com/journal/molecules


*Edited by Manuel Oliveira and Anabela Fernandes-Silva*

How plants adapt to climate change is a complex and multifaceted process and understanding it requires a comprehensive knowledge of plant biology and ecology. Some of the most serious stresses that plants face include heat and water stress, soil degradation, and increased pests and diseases. Addressing these challenges is crucial to preserve lives and livelihoods and requires a combination of scientific research, technical innovations, and policy interventions to increase ecosystem resilience and sustainable agricultural practices. This book is a step in the right direction, as it provides a comprehensive overview of plant adaptation to abiotic stresses.

ISBN 978-1-83768-496-0

Abiotic Stress in Plants - Adaptations to Climate Change

Published in London, UK © 2023 IntechOpen © Ruth Enyedi / unsplash


Author details

The results obtained show the shift of the partial enthalpy change of mixing toward more positive values with increasing concentration of indium in the binary alloys. A threedimensional logΘLa=U � Cð Þ Ga�In � 1=Tgraph showing the relationship between La/U separation factor, In concentration in Ga-In solvent alloy, and temperature for molten Me-(Ga-In)/ 3LiCl-2KCl system is presented in Figure 8 and is described by the following equation:

The basic thermodynamic properties of lanthanum, neodymium, and uranium in liquid Ga-In and Ga-Al alloys between 723 and 823 K were determined. Low values of the activity coefficients showed strong interaction between lanthanides and the liquid alloys. The values of uranium and lanthanide separation factors showed that the alloys investigated here have considerable advantage compared to liquid cadmium. Analysis of the data obtained showed that Ga-In and Ga-Al alloys are the prospective media for application in partitioning technol-

The reported study was funded by RFBR according to the research project No. 17-03-00694.

where C is the concentration of In in Ga-In alloy (wt.%).

120 Uranium - Safety, Resources, Separation and Thermodynamic Calculation

ogies of spent nuclear fuels and nuclear waste treatment.

Figure 8. Three-dimensional logΘU/La � C(Ga–In) � 1/T graph for U/La couple.

4. Conclusions

Acknowledgements

log ΘU=La ¼ 1935 þ 184 � C � 2 � C2 =T þ 2:33 � 0:246 � C þ 0:002 � C2 (62)

Valeri Smolenski1,2\*, Alena Novoselova1,2, Alexander Bychkov3 , Vladimir Volkovich4 , Yana Luk'yanova5 and Alexander Osipenko5

\*Address all correspondence to<EMAIL_ADDRESS>
1 Institute of High-Temperature Electrochemistry UB RAS, Ekaterinburg, Russia

2 College of Materials Science and Chemical Engineering, Harbin Engineering University, Harbin, P.R. China

3 National Research Nuclear University - MEPhI, Moscow, Russia

4 Department of Rare Metals and Nanomaterials, Institute of Physics and Technology, Ural Federal University, Ekaterinburg, Russia

5 JSC "State Scientific Centre-Research Institute of Atomic Reactors", Dimitrovgrad, Russia